WEDNESDAY, May 12, 2021 (HealthDay News) -- Can feeling young at heart, or at least younger than your actual age, help older people live healthier, longer propecia miscarriage lives?. Yes, according to researchers in Germany. "Individuals who feel younger than they chronologically are seem to benefit from their younger subjective age in various aspects," explained study lead author Markus Wettstein. Surveying more than 5,000 middle-aged adults and seniors, his team found that feeling propecia miscarriage younger seems to create a protective force field against stress. And the "connection seems to work via various pathways," said Wettstein, who was a researcher with the German Centre of Gerontology in Berlin when the study was conducted.

On the one hand, he noted that stress reduction due to a youthful self-perception may translate into tangible physical benefits, including staving off the threat of systemic inflammation. Having a youthful sense of propecia miscarriage self may also shape behavior in positive ways that help to keep physical and mental well-being intact. "Individuals who feel younger [may] engage in health-protective behaviors," Wettstein said. For example, they may be more physically active than those who don't feel quite as young. In addition, perceiving oneself to be younger might also be a motivating force behind self-improvement, giving folks a greater "health-enhancing" confidence in their ability to accomplish things successfully and effectively.

The study participants' average propecia miscarriage age was 64. All were enrolled in a larger ongoing study on aging and physical and mental health. Over three years, they were asked to indicate how old they felt, how much stress they experienced, and how well they could perform basic everyday activities, such as walking, dressing and/or bathing. Overall, those who reported greater stress also indicated a greater decline in their ability to execute those routine tasks. And that association was generally found to be stronger as people aged.

But the link between stress and impairment was notably weaker among those who indicated they felt younger than their true age. In fact, feeling younger was found to be particularly protective the longer-toothed one actually got..

WEDNESDAY, May buy brand propecia online 12, 2021 (HealthDay News) -- Can feeling young at heart, or at least younger than your go to my site actual age, help older people live healthier, longer lives?. Yes, according to researchers in Germany. "Individuals who feel younger than they chronologically are seem to benefit from their younger subjective age in various aspects," explained study lead author Markus Wettstein.

Surveying more than 5,000 middle-aged adults and seniors, his team found that feeling younger seems to create buy brand propecia online a protective force field against stress. And the "connection seems to work via various pathways," said Wettstein, who was a researcher with the German Centre of Gerontology in Berlin when the study was conducted. On the one hand, he noted that stress reduction due to a youthful self-perception may translate into tangible physical benefits, including staving off the threat of systemic inflammation.

Having a youthful sense of self may also shape behavior in buy brand propecia online positive ways that help to keep physical and mental well-being intact. "Individuals who feel younger [may] engage in health-protective behaviors," Wettstein said. For example, they may be more physically active than those who don't feel quite as young.

In addition, perceiving oneself to be younger might also be a motivating force behind self-improvement, giving folks a greater "health-enhancing" confidence in their ability to accomplish things successfully and effectively. The study participants' average age was 64 buy brand propecia online. All were enrolled in a larger ongoing study on aging and physical and mental health.

Over three years, they were asked to indicate how old they felt, how much stress they experienced, and how well they could perform basic everyday activities, such as walking, dressing and/or bathing. Overall, those who reported buy brand propecia online greater stress also indicated a greater decline in their ability to execute those routine tasks. And that association was generally found to be stronger as people aged.

But the link between stress and impairment was notably weaker among those who indicated they felt younger than their true age. In fact, feeling younger was found to be particularly protective the longer-toothed one actually got..

What should I watch for while taking Propecia?

Do not donate blood until at least 6 months after your final dose of finasteride. This will prevent giving finasteride to a pregnant female through a blood transfusion.

Contact your prescriber or health care professional if there is no improvement in your symptoms. You may need to take finasteride for 6 to 12 months to get the best results.

Women who are pregnant or may get pregnant must not handle broken or crushed finasteride tablets; the active ingredient could harm the unborn baby. If a pregnant woman comes into contact with broken or crushed finasteride tablets she should check with her prescriber or health care professional. Exposure to whole tablets is not expected to cause harm as long as they are not swallowed.

Finasteride can interfere with PSA laboratory tests for prostate cancer. If you are scheduled to have a lab test for prostate cancer, tell your prescriber or health care professional that you are taking finasteride.

Propecia for hair loss amazon

IntroductionMinecraft is a computer game with no propecia for hair loss amazon specific goals to accomplish. The gameworld consists of three-dimensional (3D) cubes and objects which the player (Steve) can mine and build into infinitely complex (and logically impossible) structures. Steve sometimes propecia for hair loss amazon encounters other characters (‘mobs’), such as animals and hostile creatures.

He can ‘spawn’ and destroy them. While it looks like a harmless game of logical construction, it conveys some worryingly delusive ideas about the real world. The difference between real and imagined propecia for hair loss amazon structures is at the heart of the age-old debate around categorising mental disorders.Classification in mental health has had various forms throughout history.

Mack and colleagues set out a history of psychiatric classification beginning in 2600 BC with Egyptian references to melancholia and hysteria. Through the propecia for hair loss amazon Ancient Greeks with Hippocrates’ phrenitis, mania, melancholia, epilepsy, hysteria and Scythian disease. Through the Renaissance period.

Through to 19th-century psychiatry featuring Pinel (known as the first psychiatrist), Kraepelin (known for observational classification) and Freud (known for classifying neurosis and psychosis).1Although the history of psychiatric classification identifies some common trends such as the labels ‘melancholia’ and ‘hysteria’ which have survived millennia, the label ‘depression’ is relatively new. The earliest propecia for hair loss amazon usage noted by Snaith is from 1899. €˜in simple pathological depression…the patient exhibits a growing indifference to his former pursuits…’.2 Snaith noted that early 20th-century psychiatrists like Adolf Meyer hoped that ‘depression’ would come to encompass a broad category under which descriptions of subtypes would emerge.

This did not happen until the middle of the propecia for hair loss amazon 20th century. With the publication of the sixth International Classification of Diseases (ICD) in 1948 and the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1952 and their subsequent revisions, the latter half of the 20th century has seen depression subtype labels proliferate. In their study of the social determinants of diagnostic labels in depression, McPherson and Armstrong illustrate how the codification of depression subtypes in the latter half of the 20th century has been shaped by the evolving context of psychiatry, including power struggles within the profession, a move to community care and the development of psychopharmacology.3During this period, McPherson and Armstrong describe how subsequent versions of the DSM served as battlegrounds for professional disputes and philosophical quarrels around categorisation of mental disorders.

DSM I and DSM II have been described as products of an American Psychiatric Association dominated by psychoanalytic psychiatrists.4 DSM III and DSM III-R have been described as a radical rejection of psychoanalytic thinking, a ‘neo-Kraepelinian propecia for hair loss amazon revolution’, a reference to the observational descriptive techniques of 19th-century psychiatrist Emil Kraepelin who classified mental disorders into two broad categories. €˜dementia praecox’ and ‘manic-depression’.5 DSM III was seen by some as a turning point in the use of the medical model of mental illness, through provision of specific inclusion and exclusion criteria, and use of field trials and a multiaxial system.6 These latter technocratic additions to psychiatric labelling served to engender a much closer alignment between psychiatry, science and medicine.The codification of mental disorders in manuals has been described by Thomas Schacht as intrinsic to the relationship between science and politics and the way in which psychiatrists gain significant social power by aligning themselves to science.7 His argument drew on Szasz, who saw the mental health establishment as a therapeutic state. Zimbardo, who described psychiatric care as a controlling force propecia for hair loss amazon.

And Foucault, who described the categorisation of the mentally ill as a force for isolating ‘the other’. Diagnostic critique has been further developed through a cultural relativist lens in that what Western psychiatrists classify as a depression is constructed differently in other cultures.8 Considering these limitations, some critics have gone so far as to argue that psychiatric diagnostic systems should be abolished.9Yet architects of DSM manuals have worked hard to ensure the technology of classification is regarded as genuine scientific activity with sound roots in philosophy of science. In their philosophical defence of DSM IV, Allen Frances and propecia for hair loss amazon colleagues address their critics under the headings ‘nominalism vs realism’, ‘empiricism vs rationalism’ and ‘categorical vs dimensional’.10 The implication is that there are opposing stances in which a choice must be made or a middle ground forged by those reasonable enough to recognise the need for pragmatism in the service of clinical utility.

The nominalism–realism debate is illustrated using as metaphor three different stances a cricket umpire might take on calling strikes and balls. The discussion sets out two of propecia for hair loss amazon these as extreme views. €˜at one extreme…those who take a reductionistically realistic view of the world’ versus ‘the solipsistic nominalists…might content that nothing exists’.

Szasz, who is characterised as holding particularly extreme views, is named as an archetypal solipsist. There is implied to be a degree of arrogance associated with this view in the illustrative example in which the umpire states ‘there are no balls and there are no strikes until I call propecia for hair loss amazon them’. Frances therefore sets up a means of grouping two kinds of people as philosophical extremists who can be dismissed, while avoiding addressing the philosophical problems they pose.Frances provides little if any justification for the middle ground stance, ‘There are balls and there are strikes and I call them as I see them’, other than to focus on its clinical utility and the lack of clinical utility in the alternatives ‘naïve realism’ and ‘heuristically barren solipsism’.

The natural conclusion the reader is invited to reach is that a middle ground of a heuristic concept is naturally right because it is not extreme and is naturally useful clinically, without specifying in what way this stance is coherent, resolves the two alternatives, and in what way propecia for hair loss amazon a heuristic construct that is not ‘real’ can be subject to scientific testing.Similarly, in discussing the ‘categorical vs dimensional’, Frances promotes the ‘prototype approach’. Those holding opposing views are labelled as ‘dualists’ or ‘dichotomisers’. The prototypical approach is again put forward as a clinically useful middle ground.

Illustrations are drawn from propecia for hair loss amazon natural science. €˜a triangle and a square are never the same’, inciting the reader to consider science as value-free. The prototypical approach emerges as a natural solution, yet the authors do not address how a diagnostic prototype resolves the issues posed by the two propecia for hair loss amazon alternatives, nor how a prototype can be subjected to natural science methods.The argument presented here is not a defence of solipsism or dualism.

Rather it aims to illustrate that if for pragmatic purposes clinicians and policymakers choose to gloss over the philosophical flaws in classification practices, it is then risky to move beyond the heuristic and apply natural science methods to these constructs adding multiple layers of technocratic subclassification. Doing so is more like playing Minecraft than cricket. The National Institute for Health and Care Excellence (NICE) guideline for depression is taken as an example of the philosophical errors that can follow from playing Minecraft with unsound heuristic devices, specifically subcategories of propecia for hair loss amazon persistent forms of depression.

As well as serving a clinical purpose, diagnosis in medicine is a way of allocating resources for insurance companies and constructing clinical guidelines, which in turn determine rationing within the National Health Service. The consequences for recipients of healthcare propecia for hair loss amazon are therefore significant. Clinical utility is arguably not being served at all and patients are left at risk of poor-quality care.Heterogeneity of persistent depressionAndrea Jobst and colleagues note that ‘because of their chronic clinical course, approximately 40% of CD [chronic depression] patients also fulfil criteria for TRD [treatment resistant depression]…usually defined by the number of non-successful biological treatments’.11 This position is reflected in the DSM VAmerican Psychiatric Association (2013), the European Psychiatric Association (EPA) guidance and the ICD-11(World Health Organisation, 2018), which all use a ‘persistent’ depression category, acknowledging a loosely defined mixed group of long-term, difficult-to-treat depressive conditions, often associated with dysthymia and comorbid common mental disorders, various personality traits and psychosocial disability.In contrast, the NICE 2018 draft guideline separates treatments into those for ‘new episodes’ of depression.

€˜further-line’ treatment of depression (equivalent to TRD), CD and ‘depression with co-morbidities’. The latter is subdivided into treatments for ‘complex depression’ and propecia for hair loss amazon ‘psychotic depression’. These categories and subcategories introduce an unfortunate sense of certainty as though these labels represent real things.

An analysis follows of how these definitions play out in terms of grouping of randomised controlled trials in the NICE evidence review propecia for hair loss amazon. Specifically, the analysis reveals the overlap between populations in trials which have been separated into discrete categories, revealing significant limitations to the utility of the category labels.The NICE definition of CD requires trial samples to meet the criteria for major depressive disorder (MDD) for 2 years. Dysthymia and double depression (MDD superimposed on dysthymia) were included.

If 75% of the trial population met these criteria, the trial was reviewed in the CD category.12 The definition of TRD (or ‘further-line treatments’) required that the trial sample had demonstrated a ‘limited response to previous treatment’ and randomised to the propecia for hair loss amazon further-line treatment at this point. If 80% of the trial participants met these criteria, it was reviewed in the TRD category.13 Complex depression was defined as ‘depression co-existing with personality disorder’. To be classed as complex, 51% of trial participants had to have personality propecia for hair loss amazon disorder (PD).14It is immediately clear from these definitions that there is a potential problem with attempting to categorise trial populations into just one of these categories.

These populations are likely to overlap, whether or not a trial protocol sets out to explicitly record all of this information. The analysis below will illustrate this using examples from within the NICE review.Cataloguing complexity in trial populationsWithin the category of further-line treatments (TRD), 64 trials were reviewed. Comparisons within these trials were further propecia for hair loss amazon subcategorised into ‘dose escalation strategies’, ‘augmentation strategies’ and ‘switching strategies’.

In drilling down by way of illustration, this analysis considers the 51 trials in the augmentation strategy evidence review. Of these, propecia for hair loss amazon two were classified by the reviewers as also fulfilling the criteria for CD but were not analysed in the CD category (Study IDs. Fonagy 2015 and Kocsis 200915).

About half of the trials (23/51) did not report the mean duration of episode, meaning that it is not possible to know what percentage of participants also met the criteria for CD. Of trials propecia for hair loss amazon that did report episode duration, 17 reported a mean duration longer than 24 months. While the standard deviations varied in size or were unreported, the mean indicates a good likelihood that a significant proportion of the participants across these 51 trials met the criteria for CD.Details of baseline employment, trauma history, suicidality, physical comorbidity, axis I comorbidity and PD (all clinical indicators of complexity, severity and chronicity) were not collated by NICE.

For the present analysis, all 51 publications were examined and data compiled concerning clinical complexity in the trial populations. Only 14 of 51 trials report employment data propecia for hair loss amazon. Of those that do, unemployment ranges from 12% to 56% across trial samples.

None of propecia for hair loss amazon the trials report trauma history. About half of the trials (26/51) excluded people who were considered a suicide risk. The others did not.A large proportion of trials (30/51) did not provide any data on axis 1 comorbidity.

Of these, 18 did not exclude any diagnoses, while 12 propecia for hair loss amazon excluded some (but not all) disorders. The most common diagnoses excluded were psychotic disorders, substance or alcohol abuse, and bipolar disorder (excluded in 26, 25 and 23 trials, respectively). Only 7 of 51 trials clearly stated that all axis 1 diagnoses were propecia for hair loss amazon excluded.

This leaves only 13 studies providing any data about comorbidity. Of these, 9 gave partial data on one or two conditions, while 4 reported either the mean number of disorders (range 1.96–2.9) or the percentage of participants (range 68.1–96.7) with any comorbid diagnosis (Nierenberg 2003a, Nierenberg 2006, Watkins 2011a, Town 201715).The majority of trials (46/51) did not report the prevalence of PD. Many stated PD as an exclusion criterion propecia for hair loss amazon but without defining a threshold for exclusion.

For example, PD could be excluded if it ‘impacted’ the depression, if it was ‘significant’, ‘severe’ or ‘persistent’. Some excluded certain PDs (such as antisocial or borderline) and not others but without reporting propecia for hair loss amazon the prevalence of those not excluded. In the five trials where prevalence was clear, prevalence ranged from 0% (Ravindran 2008a15), where all PDs were excluded, to 87.5% of the sample (Town 201715).

Two studies reported the mean number of PDs. 2.0 (Nierenberg propecia for hair loss amazon 2003a) and 0.85 (Watkins 2011a15).The majority of trials (43/51) did not report the prevalence of physical illness. Many stated illness as an exclusion criterion, but the definitions and thresholds were vague and could be interpreted in different ways.

For example, illness could be excluded if it was ‘unstable’, ‘serious’, ‘significant’, ‘relevant’, or would ‘contraindicate’ or ‘impact’ the propecia for hair loss amazon medication. Of the eight trials reporting information about physical health, there was a wide variation. Four reported prevalence varying from 7.6% having a disability (Eisendrath 201615) to 90.9% having an illness or disability (Town 201715).

Four used scales of physical propecia for hair loss amazon health. Two indicating mild problems (Nierenberg 2006, Lavretsky 201115) and two indicating moderately high levels of illness (Thase 2007, Fang 201015).The NICE review also divided trial populations into a dichotomy of ‘more severe’ and ‘less severe’ on the grounds that this would be a clinically useful classification for general practitioners. NICE applied a bespoke methodology for creating this dichotomy, abandoning validated measure thresholds in order first to generate two ‘homogeneous’ groups to ‘facilitate analysis’, and second to create propecia for hair loss amazon an algorithm to ‘read across’ different measures (such as the Beck Depression Inventory, the Hamilton Rating Scale for Depression (HRSD) and the Montgomery-Asberg Depression Rating Scale).16 Examining trials which use more than one of these measures reveals problems in the algorithm.

Of the 51 trials, there are 6 instances in which the study population falls into NICE’s more severe category according to one measure and into the less severe category according to another. In four of these trials, NICE chose the less severe category (Souza 2016, Watkins 2011a, Fonagy 2015, Town 201715). The other propecia for hair loss amazon two trials were designated more severe (Barbee 2011, Dunner 200715).

Only 17 of 51 trials reported two or more depression scale measures, leaving much unknown about whether other study populations could count as both more severe and less severe.Absence of knowledge or knowledge of absence?. A key philosophical error in science propecia for hair loss amazon is to confuse an absence of knowledge with knowledge of absence. It is likely that some of the study populations deemed lacking in complexity or severity could actually have high degrees of complexity and/or severity.

Data to demonstrate this may either fall foul of a guideline committee decision to prioritise certain information over other conflicting information (as in the severity algorithm). The information propecia for hair loss amazon may be non-existent as it was not collected. It may be somewhere in the publication pipeline.

Or it may be sitting in a database with a research team that has run out of funds for propecia for hair loss amazon supplementary analyses. Wherever those data are or are not, their absence from published articles does not define the phenomenology of depression for the patients who took part. As a case in point, data from the Fonagy 2015 trial presented at conferences but not published reveal that PD prevalence data would place the trial well within the NICE complex depression category, and that the sample had high levels of past trauma and physical condition comorbidity.

The trial also meets the guideline criteria for CD according to the guideline’s own appendices.17 Reported axis 1 comorbidity propecia for hair loss amazon was high (75.2% had anxiety disorder, 18.6% had substance abuse disorder, 13.2% had eating disorder).18 The mean depression scores at baseline were 36.5 on the Beck Depression Inventory and 20.1 on the HRSD (severe and very severe, respectively, according to published cut-off scores). NICE categorised this population as less severe TRD, not CD and not complex.Notes1. Avram H propecia for hair loss amazon.

Mack et al. (1994), “A Brief History of Psychiatric Classification. From the Ancients to DSM-IV,” Psychiatric Clinics 17, no propecia for hair loss amazon.

P. Snaith (1987), “The Concepts of Mild Depression,” British Journal of Psychiatry 150, no. 3.

387.3. Susan McPherson and David Armstrong (2006), “Social Determinants of Diagnostic Labels in Depression,” Social Science &. Medicine 62, no.

Grob (1991), “Origins of DSM-I. A Study in Appearance and Reality,” The American Journal of Psychiatry. 421–31.5.

Wilson M. Compton and Samuel B. Guze (1995), “The Neo-Kraepelinian Revolution in Psychiatric Diagnosis,” European Archives of Psychiatry and Clinical Neuroscience 245, no.

Klerman (1984), “A Debate on DSM-III. The Advantages of DSM-III,” The American Journal of Psychiatry. 539–42.7.

Thomas E. Schacht (1985), “DSM-III and the Politics of Truth,” American Psychologist. 513–5.8.

Daniel F. Hartner and Kari L. Theurer (2018), “Psychiatry Should Not Seek Mechanisms of Disorder,” Journal of Theoretical and Philosophical Psychology 38, no.

4. 189–204.9. Sami Timimi (2014), “No More Psychiatric Labels.

Why Formal Psychiatric Diagnostic Systems Should Be Abolished,” Journal of Clinical and Health Psychology 14, no. 3. 208–15.10.

Allen Frances et al. (1994), “DSM-IV Meets Philosophy,” The Journal of Medicine and Philosophy. A Forum for Bioethics and Philosophy of Medicine 19, no.

(2016), “European Psychiatric Association Guidance on Psychotherapy in Chronic Depression Across Europe,” European Psychiatry 33. 20.12. National Institute for Health and Care Excellence (2018), Depression in Adults.

Treatment and Management. Draft for Consultation, https://www.nice.org.uk/guidance/gid-cgwave0725/documents/full-guideline-updated, 507.13. Ibid., 351–62.14.

Ibid., 597.15. Note that in order to refer to specific trials reviewed in the guideline, rather than the full citation, the Study IDs from column A in appendix J5 have been used. See www.nice.org.uk/guidance/gid-cgwave0725/documents/addendum-appendix-9 for details and full references.16.

National Institute for Health and Care Excellence (2018), Depression in Adults. Treatment and Management. Second Consultation on Draft Guideline – Stakeholder Comments Table, https://www.nice.org.uk/guidance/gid-cgwave0725/documents/consultation-comments-and-responses-2, 420–1.17.

National Institute for Health and Care Excellence (2018), Depression in Adults, appendix J5.18. Peter Fonagy et al. (2015), “Pragmatic Randomized Controlled Trial of Long-Term Psychoanalytic Psychotherapy for Treatment-Resistant Depression.

The Tavistock Adult Depression Study (TADS),” World Psychiatry 14, no. 3. 312–21.19.

American Psychological Association (2018), Clinical Practice Guideline for the Treatment of Depression in Children, Adolescents, and Young, Middle-aged, and Older Adults. Draft.20. Jacqui Thornton (2018), “Depression in Adults.

Campaigners and Doctors Demand Full Revision of NICE Guidance,” BMJ 361. K2681..

IntroductionMinecraft is a computer game with http://www.mbstoday.org/the-iron-sharpens-iron-mens-conference-was-a-great-success/ no specific goals buy brand propecia online to accomplish. The gameworld consists of three-dimensional (3D) cubes and objects which the player (Steve) can mine and build into infinitely complex (and logically impossible) structures. Steve sometimes buy brand propecia online encounters other characters (‘mobs’), such as animals and hostile creatures.

He can ‘spawn’ and destroy them. While it looks like a harmless game of logical construction, it conveys some worryingly delusive ideas about the real world. The difference between real and imagined structures is at the heart of the age-old debate around categorising mental disorders.Classification in mental health has had buy brand propecia online various forms throughout history.

Mack and colleagues set out a history of psychiatric classification beginning in 2600 BC with Egyptian references to melancholia and hysteria. Through the Ancient Greeks with Hippocrates’ phrenitis, mania, melancholia, epilepsy, buy brand propecia online hysteria and Scythian disease. Through the Renaissance period.

Through to 19th-century psychiatry featuring Pinel (known as the first psychiatrist), Kraepelin (known for observational classification) and Freud (known for classifying neurosis and psychosis).1Although the history of psychiatric classification identifies some common trends such as the labels ‘melancholia’ and ‘hysteria’ which have survived millennia, the label ‘depression’ is relatively new. The earliest usage noted by Snaith buy brand propecia online is from 1899. €˜in simple pathological depression…the patient exhibits a growing indifference to his former pursuits…’.2 Snaith noted that early 20th-century psychiatrists like Adolf Meyer hoped that ‘depression’ would come to encompass a broad category under which descriptions of subtypes would emerge.

This did not happen until buy brand propecia online the middle of the 20th century. With the publication of the sixth International Classification of Diseases (ICD) in 1948 and the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1952 and their subsequent revisions, the latter half of the 20th century has seen depression subtype labels proliferate. In their study of the social determinants of diagnostic labels in depression, McPherson and Armstrong illustrate how the codification of depression subtypes in the latter half of the 20th century has been shaped by the evolving context of psychiatry, including power struggles within the profession, a move to community care and the development of psychopharmacology.3During this period, McPherson and Armstrong describe how subsequent versions of the DSM served as battlegrounds for professional disputes and philosophical quarrels around categorisation of mental disorders.

DSM I and DSM II have been described as products of an American Psychiatric buy brand propecia online Association dominated by psychoanalytic psychiatrists.4 DSM III and DSM III-R have been described as a radical rejection of psychoanalytic thinking, a ‘neo-Kraepelinian revolution’, a reference to the observational descriptive techniques of 19th-century psychiatrist Emil Kraepelin who classified mental disorders into two broad categories. €˜dementia praecox’ and ‘manic-depression’.5 DSM III was seen by some as a turning point in the use of the medical model of mental illness, through provision of specific inclusion and exclusion criteria, and use of field trials and a multiaxial system.6 These latter technocratic additions to psychiatric labelling served to engender a much closer alignment between psychiatry, science and medicine.The codification of mental disorders in manuals has been described by Thomas Schacht as intrinsic to the relationship between science and politics and the way in which psychiatrists gain significant social power by aligning themselves to science.7 His argument drew on Szasz, who saw the mental health establishment as a therapeutic state. Zimbardo, who described psychiatric care as a controlling buy brand propecia online force.

And Foucault, who described the categorisation of the mentally ill as a force for isolating ‘the other’. Diagnostic critique has been further developed through a cultural relativist lens in that what Western psychiatrists classify as a depression is constructed differently in other cultures.8 Considering these limitations, some critics have gone so far as to argue that psychiatric diagnostic systems should be abolished.9Yet architects of DSM manuals have worked hard to ensure the technology of classification is regarded as genuine scientific activity with sound roots in philosophy of science. In their buy brand propecia online philosophical defence of DSM IV, Allen Frances and colleagues address their critics under the headings ‘nominalism vs realism’, ‘empiricism vs rationalism’ and ‘categorical vs dimensional’.10 The implication is that there are opposing stances in which a choice must be made or a middle ground forged by those reasonable enough to recognise the need for pragmatism in the service of clinical utility.

The nominalism–realism debate is illustrated using as metaphor three different stances a cricket umpire might take on calling strikes and balls. The discussion sets out two of these buy brand propecia online as extreme views. €˜at one extreme…those who take a reductionistically realistic view of the world’ versus ‘the solipsistic nominalists…might content that nothing exists’.

Szasz, who is characterised as holding particularly extreme views, is named as an archetypal solipsist. There is buy brand propecia online implied to be a degree of arrogance associated with this view in the illustrative example in which the umpire states ‘there are no balls and there are no strikes until I call them’. Frances therefore sets up a means of grouping two kinds of people as philosophical extremists who can be dismissed, while avoiding addressing the philosophical problems they pose.Frances provides little if any justification for the middle ground stance, ‘There are balls and there are strikes and I call them as I see them’, other than to focus on its clinical utility and the lack of clinical utility in the alternatives ‘naïve realism’ and ‘heuristically barren solipsism’.

The natural conclusion the reader is invited to reach is that a middle ground of a heuristic concept is naturally right because it is not extreme and is naturally useful clinically, without specifying in what way this stance is coherent, resolves the two alternatives, and in what way a heuristic construct that is not ‘real’ can be subject to scientific testing.Similarly, in discussing the ‘categorical vs dimensional’, Frances promotes the ‘prototype approach’ buy brand propecia online. Those holding opposing views are labelled as ‘dualists’ or ‘dichotomisers’. The prototypical approach is again put forward as a clinically useful middle ground.

Illustrations are drawn from buy brand propecia online natural science. €˜a triangle and a square are never the same’, inciting the reader to consider science as value-free. The prototypical approach emerges as buy brand propecia online a natural solution, yet the authors do not address how a diagnostic prototype resolves the issues posed by the two alternatives, nor how a prototype can be subjected to natural science methods.The argument presented here is not a defence of solipsism or dualism.

Rather it aims to illustrate that if for pragmatic purposes clinicians and policymakers choose to gloss over the philosophical flaws in classification practices, it is then risky to move beyond the heuristic and apply natural science methods to these constructs adding multiple layers of technocratic subclassification. Doing so is more like playing Minecraft than cricket. The National Institute for Health and Care Excellence (NICE) guideline for depression is taken as an example of the philosophical errors that can follow buy brand propecia online from playing Minecraft with unsound heuristic devices, specifically subcategories of persistent forms of depression.

As well as serving a clinical purpose, diagnosis in medicine is a way of allocating resources for insurance companies and constructing clinical guidelines, which in turn determine rationing within the National Health Service. The consequences for buy brand propecia online recipients of healthcare are therefore significant. Clinical utility is arguably not being served at all and patients are left at risk of poor-quality care.Heterogeneity of persistent depressionAndrea Jobst and colleagues note that ‘because of their chronic clinical course, approximately 40% of CD [chronic depression] patients also fulfil criteria for TRD [treatment resistant depression]…usually defined by the number of non-successful biological treatments’.11 This position is reflected in the DSM VAmerican Psychiatric Association (2013), the European Psychiatric Association (EPA) guidance and the ICD-11(World Health Organisation, 2018), which all use a ‘persistent’ depression category, acknowledging a loosely defined mixed group of long-term, difficult-to-treat depressive conditions, often associated with dysthymia and comorbid common mental disorders, various personality traits and psychosocial disability.In contrast, the NICE 2018 draft guideline separates treatments into those for ‘new episodes’ of depression.

€˜further-line’ treatment of depression (equivalent to TRD), CD and ‘depression with co-morbidities’. The latter is subdivided into treatments for buy brand propecia online ‘complex depression’ and ‘psychotic depression’. These categories and subcategories introduce an unfortunate sense of certainty as though these labels represent real things.

An analysis follows of how these buy brand propecia online definitions play out in terms of grouping of randomised controlled trials in the NICE evidence review. Specifically, the analysis reveals the overlap between populations in trials which have been separated into discrete categories, revealing significant limitations to the utility of the category labels.The NICE definition of CD requires trial samples to meet the criteria for major depressive disorder (MDD) for 2 years. Dysthymia and double depression (MDD superimposed on dysthymia) were included.

If 75% of the trial population met these criteria, the trial was reviewed in the CD category.12 The definition of TRD (or ‘further-line treatments’) required that the trial sample had demonstrated a ‘limited response buy brand propecia online to previous treatment’ and randomised to the further-line treatment at this point. If 80% of the trial participants met these criteria, it was reviewed in the TRD category.13 Complex depression was defined as ‘depression co-existing with personality disorder’. To be classed as complex, 51% of trial participants had to have personality disorder (PD).14It is immediately clear from these definitions that there is a potential problem with attempting to categorise trial buy brand propecia online populations into just one of these categories.

These populations are likely to overlap, whether or not a trial protocol sets out to explicitly record all of this information. The analysis below will illustrate this using examples from within the NICE review.Cataloguing complexity in trial populationsWithin the category of further-line treatments (TRD), 64 trials were reviewed. Comparisons within these trials were further subcategorised into ‘dose escalation strategies’, ‘augmentation strategies’ and ‘switching buy brand propecia online strategies’.

In drilling down by way of illustration, this analysis considers the 51 trials in the augmentation strategy evidence review. Of these, two were classified by the reviewers as buy brand propecia online also fulfilling the criteria for CD but were not analysed in the CD category (Study IDs. Fonagy 2015 and Kocsis 200915).

About half of the trials (23/51) did not report the mean duration of episode, meaning that it is not possible to know what percentage of participants also met the criteria for CD. Of trials that did report buy brand propecia online episode duration, 17 reported a mean duration longer than 24 months. While the standard deviations varied in size or were unreported, the mean indicates a good likelihood that a significant proportion of the participants across these 51 trials met the criteria for CD.Details of baseline employment, trauma history, suicidality, physical comorbidity, axis I comorbidity and PD (all clinical indicators of complexity, severity and chronicity) were not collated by NICE.

For the present analysis, all 51 publications were examined and data compiled concerning clinical complexity in the trial populations. Only 14 buy brand propecia online of 51 trials report employment data. Of those that do, unemployment ranges from 12% to 56% across trial samples.

None of the trials report trauma buy brand propecia online history. About half of the trials (26/51) excluded people who were considered a suicide risk. The others did not.A large proportion of trials (30/51) did not provide any data on axis 1 comorbidity.

Of these, 18 did not exclude any diagnoses, while buy brand propecia online 12 excluded some (but not all) disorders. The most common diagnoses excluded were psychotic disorders, substance or alcohol abuse, and bipolar disorder (excluded in 26, 25 and 23 trials, respectively). Only 7 of 51 trials clearly stated buy brand propecia online that all axis 1 diagnoses were excluded.

This leaves only 13 studies providing any data about comorbidity. Of these, 9 gave partial data on one or two conditions, while 4 reported either the mean number of disorders (range 1.96–2.9) or the percentage of participants (range 68.1–96.7) with any comorbid diagnosis (Nierenberg 2003a, Nierenberg 2006, Watkins 2011a, Town 201715).The majority of trials (46/51) did not report the prevalence of PD. Many stated PD buy brand propecia online as an exclusion criterion but without defining a threshold for exclusion.

For example, PD could be excluded if it ‘impacted’ the depression, if it was ‘significant’, ‘severe’ or ‘persistent’. Some excluded certain PDs (such as antisocial or buy brand propecia online borderline) and not others but without reporting the prevalence of those not excluded. In the five trials where prevalence was clear, prevalence ranged from 0% (Ravindran 2008a15), where all PDs were excluded, to 87.5% of the sample (Town 201715).

Two studies reported the mean number of PDs. 2.0 (Nierenberg 2003a) and 0.85 (Watkins 2011a15).The majority of trials buy brand propecia online (43/51) did not report the prevalence of physical illness. Many stated illness as an exclusion criterion, but the definitions and thresholds were vague and could be interpreted in different ways.

For example, illness could be excluded if it was ‘unstable’, ‘serious’, ‘significant’, ‘relevant’, or would ‘contraindicate’ or ‘impact’ the buy brand propecia online medication. Of the eight trials reporting information about physical health, there was a wide variation. Four reported prevalence varying from 7.6% having a disability (Eisendrath 201615) to 90.9% having an illness or disability (Town 201715).

Four used scales of physical buy brand propecia online health. Two indicating mild problems (Nierenberg 2006, Lavretsky 201115) and two indicating moderately high levels of illness (Thase 2007, Fang 201015).The NICE review also divided trial populations into a dichotomy of ‘more severe’ and ‘less severe’ on the grounds that this would be a clinically useful classification for general practitioners. NICE applied a bespoke methodology for creating this dichotomy, abandoning validated measure thresholds buy brand propecia online in order first to generate two ‘homogeneous’ groups to ‘facilitate analysis’, and second to create an algorithm to ‘read across’ different measures (such as the Beck Depression Inventory, the Hamilton Rating Scale for Depression (HRSD) and the Montgomery-Asberg Depression Rating Scale).16 Examining trials which use more than one of these measures reveals problems in the algorithm.

Of the 51 trials, there are 6 instances in which the study population falls into NICE’s more severe category according to one measure and into the less severe category according to another. In four of these trials, NICE chose the less severe category (Souza 2016, Watkins 2011a, Fonagy 2015, Town 201715). The other two buy brand propecia online trials were designated more severe (Barbee 2011, Dunner 200715).

Only 17 of 51 trials reported two or more depression scale measures, leaving much unknown about whether other study populations could count as both more severe and less severe.Absence of knowledge or knowledge of absence?. A key philosophical error in science is buy brand propecia online to confuse an absence of knowledge with knowledge of absence. It is likely that some of the study populations deemed lacking in complexity or severity could actually have high degrees of complexity and/or severity.

Data to demonstrate this may either fall foul of a guideline committee decision to prioritise certain information over other conflicting information (as in the severity algorithm). The information buy brand propecia online may be non-existent as it was not collected. It may be somewhere in the publication pipeline.

Or it may be sitting buy brand propecia online in a database with a research team that has run out of funds for supplementary analyses. Wherever those data are or are not, their absence from published articles does not define the phenomenology of depression for the patients who took part. As a case in point, data from the Fonagy 2015 trial presented at conferences but not published reveal that PD prevalence data would place the trial well within the NICE complex depression category, and that the sample had high levels of past trauma and physical condition comorbidity.

The trial also meets the guideline criteria for CD according to the guideline’s own appendices.17 Reported axis 1 comorbidity was high (75.2% had anxiety disorder, 18.6% had substance abuse disorder, 13.2% had eating disorder).18 The mean depression buy brand propecia online scores at baseline were 36.5 on the Beck Depression Inventory and 20.1 on the HRSD (severe and very severe, respectively, according to published cut-off scores). NICE categorised this population as less severe TRD, not CD and not complex.Notes1. Avram H buy brand propecia online.

Mack et al. (1994), “A Brief History of Psychiatric Classification. From the Ancients to DSM-IV,” Psychiatric Clinics 17, buy brand propecia online no.

P. Snaith (1987), “The Concepts of Mild Depression,” British Journal of Psychiatry 150, no. 3.

387.3. Susan McPherson and David Armstrong (2006), “Social Determinants of Diagnostic Labels in Depression,” Social Science &. Medicine 62, no.

Grob (1991), “Origins of DSM-I. A Study in Appearance and Reality,” The American Journal of Psychiatry. 421–31.5.

Wilson M. Compton and Samuel B. Guze (1995), “The Neo-Kraepelinian Revolution in Psychiatric Diagnosis,” European Archives of Psychiatry and Clinical Neuroscience 245, no.

Klerman (1984), “A Debate on DSM-III. The Advantages of DSM-III,” The American Journal of Psychiatry. 539–42.7.

Thomas E. Schacht (1985), “DSM-III and the Politics of Truth,” American Psychologist. 513–5.8.

Daniel F. Hartner and Kari L. Theurer (2018), “Psychiatry Should Not Seek Mechanisms of Disorder,” Journal of Theoretical and Philosophical Psychology 38, no.

4. 189–204.9. Sami Timimi (2014), “No More Psychiatric Labels.

Why Formal Psychiatric Diagnostic Systems Should Be Abolished,” Journal of Clinical and Health Psychology 14, no. 3. 208–15.10.

Allen Frances et al. (1994), “DSM-IV Meets Philosophy,” The Journal of Medicine and Philosophy. A Forum for Bioethics and Philosophy of Medicine 19, no.

(2016), “European Psychiatric Association Guidance on Psychotherapy in Chronic Depression Across Europe,” European Psychiatry 33. 20.12. National Institute for Health and Care Excellence (2018), Depression in Adults.

Treatment and Management. Draft for Consultation, https://www.nice.org.uk/guidance/gid-cgwave0725/documents/full-guideline-updated, 507.13. Ibid., 351–62.14.

Ibid., 597.15. Note that in order to refer to specific trials reviewed in the guideline, rather than the full citation, the Study IDs from column A in appendix J5 have been used. See www.nice.org.uk/guidance/gid-cgwave0725/documents/addendum-appendix-9 for details and full references.16.

National Institute for Health and Care Excellence (2018), Depression in Adults. Treatment and Management. Second Consultation on Draft Guideline – Stakeholder Comments Table, https://www.nice.org.uk/guidance/gid-cgwave0725/documents/consultation-comments-and-responses-2, 420–1.17.

National Institute for Health and Care Excellence (2018), Depression in Adults, appendix J5.18. Peter Fonagy et al. (2015), “Pragmatic Randomized Controlled Trial of Long-Term Psychoanalytic Psychotherapy for Treatment-Resistant Depression.

The Tavistock Adult Depression Study (TADS),” World Psychiatry 14, no. 3. 312–21.19.

American Psychological Association (2018), Clinical Practice Guideline for the Treatment of Depression in Children, Adolescents, and Young, Middle-aged, and Older Adults. Draft.20. Jacqui Thornton (2018), “Depression in Adults.

Campaigners and Doctors Demand Full Revision of NICE Guidance,” BMJ 361. K2681..

Bradley cooper propecia

Participants Figure 1 bradley cooper propecia. Figure 1. Enrollment and bradley cooper propecia Randomization. The diagram represents all enrolled participants through November 14, 2020.

The safety subset (those with a median bradley cooper propecia of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1. Table 1 bradley cooper propecia. Demographic Characteristics of the Participants in the Main Safety Population.

Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, bradley cooper propecia 130 sites. Argentina, 1. Brazil, 2 bradley cooper propecia. South Africa, 4.

Germany, 6 bradley cooper propecia. And Turkey, 9) in the phase 2/3 portion of the trial. A total of 43,448 participants bradley cooper propecia received injections. 21,720 received BNT162b2 and 21,728 received placebo (Figure 1).

At the data cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the bradley cooper propecia height in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity Figure bradley cooper propecia 2.

Figure 2. Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 or Placebo, According to Age Group bradley cooper propecia. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel bradley cooper propecia A.

Pain at the injection site was assessed according to the following scale. Mild, does not interfere bradley cooper propecia with activity. Moderate, interferes with activity. Severe, prevents bradley cooper propecia daily activity.

And grade 4, emergency department visit or hospitalization. Redness and swelling bradley cooper propecia were measured according to the following scale. Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 bradley cooper propecia cm in diameter.

Severe, >10.0 cm in diameter. And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events bradley cooper propecia and medication use are shown in Panel B. Fever categories are designated in the key.

Medication use was not graded bradley cooper propecia. Additional scales were as follows. Fatigue, headache, chills, new or worsened muscle pain, bradley cooper propecia new or worsened joint pain (mild. Does not interfere with activity.

Moderate. Some interference with activity. Or severe. Prevents daily activity), vomiting (mild.

1 to 2 times in 24 hours. Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate. 4 to 5 loose stools in 24 hours.

Or severe. 6 or more loose stools in 24 hours). Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants.

Overall, BNT162b2 recipients reported more local reactions than placebo recipients. Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days.

Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients. 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients).

The frequency of any severe systemic event after the first dose was 0.9% or less. Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1. 38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose.

Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3).

More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%). This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo. No hair loss treatment–associated deaths were observed.

No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment. Efficacy Table 2. Table 2.

treatment Efficacy against hair loss treatment at Least 7 days after the Second Dose. Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against hair loss treatment after the First Dose. Shown is the cumulative incidence of hair loss treatment after the first dose (modified intention-to-treat population).

Each symbol represents hair loss treatment cases starting on a given day. Filled symbols represent severe hair loss treatment cases. Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days.

Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for hair loss treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior hair loss , 8 cases of hair loss treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of hair loss treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%.

95% CI, 68.7 to 99.9. Case split. BNT162b2, 2 cases. Placebo, 44 cases).

Figure 3 shows cases of hair loss treatment or severe hair loss treatment with onset at any time after the first dose (mITT population) (additional data on severe hair loss treatment are available in Table S5). Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.V-safe Surveillance. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1.

Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA hair loss treatment. Table 2. Table 2. Frequency of Local and Systemic Reactions Reported on the Day after mRNA hair loss treatment Vaccination in Pregnant Persons.

From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant. Age distributions were similar among the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively). Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1). Solicited reports of injection-site pain, fatigue, headache, and myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments.

Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments. Figure 1. Figure 1. Most Frequent Local and Systemic Reactions Reported in the V-safe Surveillance System on the Day after mRNA hair loss treatment Vaccination.

Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) hair loss disease 2019 (hair loss treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021. The percentage of respondents was calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar. Pregnant persons did not report having severe reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after dose 2 (Table S3).

V-safe Pregnancy Registry. Pregnancy Outcomes and Neonatal Outcomes Table 3. Table 3. Characteristics of V-safe Pregnancy Registry Participants.

As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after hair loss treatment vaccination. Of these, 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before the last menstrual period, or did not provide enough information to determine eligibility). The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not report a hair loss treatment diagnosis during pregnancy (97.6%) (Table 3).

Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3). Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a treatment in the second trimester, initial data had been collected and follow-up scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis. Table 4.

Table 4. Pregnancy Loss and Neonatal Outcomes in Published Studies and V-safe Pregnancy Registry Participants. Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester.

Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]). No neonatal deaths were reported at the time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received hair loss treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy and neonatal outcomes appeared similar to incidences published in the peer-reviewed literature (Table 4).

Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving hair loss treatment vaccination among pregnant persons. 155 (70.1%) involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4). The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases. 37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), followed by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each.

No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Objectives, Participants, and Oversight We conducted a randomized, placebo-controlled, observer-blinded, phase 3 trial as part of a phase 1–2–3 trial assessing BNT162b2 safety, immunogenicity, and efficacy in healthy persons 12 years of age or older. This report presents findings from 12-to-15-year-old participants enrolled in the United States, including descriptive comparisons of safety between participants in that age cohort and those who were 16 to 25 years of age and an evaluation of the noninferiority of immunogenicity in the 12-to-15-year-old cohort to that in the 16-to-25-year-old cohort. Data were collected through the cutoff date of March 13, 2021. Eligible participants were healthy or had stable preexisting disease (including hepatitis B, hepatitis C, or human immunodeficiency propecia ).

Persons with a previous clinical or virologic hair loss treatment diagnosis or hair loss , previous hair loss vaccination, diagnosis of an immunocompromising or immunodeficiency disorder, or treatment with immunosuppressive therapy (including cytotoxic agents and systemic glucocorticoids) were excluded. The ethical conduct of the trial is summarized in the Supplementary Appendix, available with the full text of this article at NEJM.org. Additional details of the trial are provided in the protocol, available at NEJM.org. Pfizer was responsible for the trial design and conduct, data collection, data analysis, data interpretation, and writing of the manuscript that was submitted.

Both Pfizer and BioNTech manufactured the treatment and placebo. BioNTech was the regulatory sponsor of the trial and contributed to data interpretation and writing of the manuscript. All data were available to the authors, who vouch for their accuracy and completeness and for the adherence of the trial to the protocol. Procedures Randomization was conducted with the use of an interactive Web-based response system.

Participants were assigned in a 1:1 ratio to receive two intramuscular injections of 30 μg of BNT162b2 or placebo (saline) 21 days apart. For evaluation of immediate treatment-associated reactions, participants were observed in the clinic for 30 minutes after vaccination. Safety Safety objectives included the assessment of local or systemic reactogenicity events, which were recorded by the participants in an electronic diary (e-diary) for 7 days after each dose. Unsolicited adverse events (i.e., those reported by the participant without e-diary prompting) and serious adverse events were also recorded from receipt of the first dose through 1 month and 6 months after dose 2, respectively.

Immunogenicity Immunogenicity assessments (hair loss serum neutralization assay and receptor-binding domain [RBD]–binding or S1-binding IgG direct Luminex immunoassays) were performed before vaccination and 1 month after dose 2, as described previously.3 The immunogenicity objective was to show noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants. Noninferiority was assessed among participants who had no evidence of previous hair loss with the use of the two-sided 95% confidence interval for the geometric mean ratio of hair loss 50% neutralizing titers in 12-to-15-year-old participants as compared with 16-to-25-year-old participants 1 month after dose 2. BNT162b2 immunogenicity was evaluated in participants with and those without serologic or virologic evidence of previous hair loss . Corresponding end points were the geometric mean hair loss neutralizing titers at baseline (i.e., immediately before receipt of the first injection) and 1 month after dose 2 and geometric mean fold rises (GMFRs) in titers from baseline to 1 month after dose 2.

Efficacy The efficacy of BNT162b2 against confirmed hair loss treatment with an onset 7 or more days after dose 2 was summarized in participants who did not have evidence of previous hair loss , as well as in all vaccinated participants. Surveillance for potential hair loss treatment cases was undertaken throughout the trial. If acute respiratory illness developed in a participant, the participant was tested for hair loss. Methods for identifying hair loss s and hair loss treatment diagnoses are summarized in the Supplementary Appendix.

Statistical Analysis The safety population included all participants who received at least one dose of BNT162b2 or placebo. The reactogenicity subset included all 12-to-15-year-old participants and a subset of 16-to-25-year-old participants (those who received an e-diary to record reactogenicity events). Safety end points are presented descriptively as counts, percentages, and associated Clopper–Pearson two-sided 95% confidence intervals, with adverse events and serious adverse events described according to terms in the Medical Dictionary for Regulatory Activities, version 23.1, for each group. Immunogenicity was assessed in a random subset of participants in each age cohort with the use of a simple random-sample selection procedure.

For immunogenicity assessments, all participants in both age cohorts were from U.S. Sites. The dose 2 immunogenicity population that could be evaluated included participants who underwent randomization and received two BNT162b2 doses in accordance with the protocol, received dose 2 within the prespecified window (19 to 42 days after dose 1), had at least one valid and determinate immunogenicity result from a blood sample obtained within 28 to 42 days after dose 2, and had no major protocol deviations. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was assessed on the basis of the geometric mean ratio of hair loss 50% neutralizing titers.

A sample of 225 BNT162b2 recipients who could be evaluated (or 280 BNT162b2 recipients overall) in each age cohort was estimated to provide 90.8% power for declaring noninferiority (defined as a lower limit of the 95% confidence interval for the geometric mean ratio of >0.67). A testing laboratory supply limitation of the qualified viral lot used for assay validation and clinical testing resulted in the trial having fewer participants than anticipated for the immunogenicity analyses. Calculations of the geometric mean ratios, geometric mean titers, and GMFRs are described in the Supplementary Appendix. Although the formal evaluation of efficacy was to be based on the overall results obtained across all age cohorts, the statistical analysis plan specified that descriptive efficacy summaries would be provided for each age cohort (the stratification factor).

The efficacy analysis for the 12-to-15-year-old cohort was planned as a descriptive analysis because the number of cases that would occur in the age subgroups was unknown. The efficacy population that could be evaluated included all eligible 12-to-15-year-old participants who underwent randomization and received two doses of BNT162b2 or placebo, received dose 2 within the prespecified window (19 to 42 days after dose 1), and had no major protocol deviations. The all-available efficacy population included all participants who received one or two doses. treatment efficacy was defined as 100×(1−IRR), where IRR is the ratio of the rate of a first confirmed hair loss treatment illness in the BNT162b2 group to the corresponding rate in the placebo group.

Two-sided Clopper–Pearson 95% confidence intervals were calculated (not adjusted for multiple comparisons). Because the number of participants who reported symptoms but were missing a valid polymerase-chain-reaction test result was small, data for these participants were not imputed in the analysis.The clinical picture of moderate-to-severe thrombocytopenia and thrombotic complications at unusual sites beginning approximately 1 to 2 weeks after vaccination against hair loss with ChAdOx1 nCov-19 suggests a disorder that clinically resembles severe heparin-induced thrombocytopenia, a well-known prothrombotic disorder caused by platelet-activating antibodies that recognize multimolecular complexes between cationic PF4 and anionic heparin.6 However, unlike the usual situation in heparin-induced thrombocytopenia, these vaccinated patients did not receive any heparin to explain the subsequent occurrence of thrombosis and thrombocytopenia. In recent years, it has been recognized that triggers other than heparin can cause a prothrombotic disorder that strongly resembles heparin-induced thrombocytopenia on both clinical and serologic grounds, including certain polyanionic drugs (e.g., pentosan polysulfate,7 antiangiogenic agent PI-88,8 and hypersulfated chondroitin sulfate8). Such a prothrombotic syndrome has also been observed in the absence of preceding exposure to any polyanionic medication, such as after both viral and bacterial s9,10 and knee-replacement surgery.11,12 These various clinical scenarios with apparent nonpharmacologic triggers have been classified under the term autoimmune heparin-induced thrombocytopenia.13 Unlike patients with classic heparin-induced thrombocytopenia, patients with autoimmune heparin-induced thrombocytopenia have unusually severe thrombocytopenia, an increased frequency of disseminated intravascular coagulation, and atypical thrombotic events.

Serum from these patients strongly activate platelets in the presence of heparin (0.1 to 1.0 IU per milliliter) but also in the absence of heparin (heparin-independent platelet activation). When these unusual antibodies are observed in patients who have thrombocytopenia without preceding heparin exposure, the term “spontaneous” heparin-induced thrombocytopenia syndrome13,14 has been used. Sometimes, patients in whom heparin-induced thrombocytopenia develops after exposure to heparin present with atypical clinical features, such as an onset of thrombocytopenia beginning several days after stopping heparin (delayed-onset heparin-induced thrombocytopenia15,16) or thrombocytopenia that persists for several weeks despite the discontinuation of heparin (persisting or refractory heparin-induced thrombocytopenia17,18). Serum from these patients also shows the phenomenon of heparin-independent platelet-activating properties.

These clinical features that resemble those of autoimmune heparin-induced thrombocytopenia were observed in the patients with treatment-induced immune thrombotic thrombocytopenia. The serum usually showed strong reactivity on the PF4–heparin ELISA. Moreover, serum showed variable degrees of platelet activation in the presence of buffer that was in most cases greatly enhanced in the presence of PF4 (Figure 1A and 1B). More strikingly, most serum showed inhibition, rather than increased activation, in the presence of low-dose low-molecular-weight heparin (0.2 U per milliliter of anti–factor Xa).

In addition, antibodies from two patients, which were affinity purified on either immobilized PF4 or immobilized PF4–heparin, strongly activated platelets but only in the presence of PF4. Enhancement of platelet activation by PF4 is also a feature of heparin-induced thrombocytopenia19,20 and has been used to enhance detection of platelet-activating antibodies in diagnostic testing for this adverse drug reaction.21 Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or antibodies induced by the treatment that cross-react with PF4 and platelets requires further study. Although we found enhanced reactivity of patient serum with platelets in the presence of ChAdOx1 nCov-19, this is likely to be an in vitro artifact. It is well known that adenopropecia binds to platelets22 and causes platelet activation.22,23 Furthermore, the amount of adenopropecia in a 500-microliter treatment injection administered 1 or 2 weeks earlier would seem unlikely to contribute to subsequent platelet activation observed in these patients.

However, interactions between the treatment and platelets or between the treatment and PF4 could play a role in pathogenesis. One possible trigger of these PF4-reactive antibodies could be free DNA in the treatment. We have previously shown that DNA and RNA form multimolecular complexes with PF4, which bind antibodies from patients with heparin-induced thrombocytopenia and also induce antibodies against PF4–heparin in a murine model.24 Unfortunately, other hair loss treatments were not available to us for testing. Our findings have several important clinical implications.

First, clinicians should be aware that in some patients, venous or arterial thrombosis can develop at unusual sites such as the brain or abdomen, which becomes clinically apparent approximately 5 to 20 days after vaccination. If such a reaction is accompanied by thrombocytopenia, it can represent an adverse effect of the preceding hair loss treatment vaccination. To date, this reaction has been reported only with the ChAdOx1 nCov-19 treatment, which has been used in approximately 25% of treatment recipients in Germany and in 30% of those in Austria. Second, ELISA to detect PF4–heparin antibodies in patients with heparin-induced thrombocytopenia is widely available and can be used to investigate patients for potential postvaccination thrombocytopenia or thrombosis associated with antibodies against PF4.25 A strongly positive ELISA result that is obtained in a patient who has not been recently exposed to heparin would be a striking abnormality.

Third, we have shown that these antibodies recognize PF4 and that the addition of PF4 greatly enhances their detectability in a platelet-activation assay. Since vaccination of millions of persons will be complicated by a background of thrombotic events unrelated to vaccination, a PF4-dependent ELISA or a PF4-enhanced platelet-activation assay may be used to confirm the diagnosis of treatment-induced immune thrombotic thrombocytopenia through this novel mechanism of postvaccination formation of platelet-activating antibodies against PF4. Although treatment decisions such as administering intravenous immune globulin and starting anticoagulation do not need to await laboratory diagnosis, detection of these unusual platelet-activating antibodies will be highly relevant for case identification and future risk–benefit assessment of this and other treatments. Figure 2.

Figure 2. Potential Diagnostic and Therapeutic Strategies for Management of Suspected treatment-Induced Immune Thrombotic Thrombocytopenia. Shown is a decision tree for the evaluation and treatment of patients who have symptoms of thrombocytopenia or thrombosis within 20 days after receiving the ChAdOx1 nCov-19 treatment and who have had no heparin exposure. The diagnostic and therapeutic strategies in such patients differ from those in patients with autoimmune heparin-induced thrombocytopenia (HIT).13 DIC denotes disseminated intravascular coagulation, INR international normalized ratio, PF4 platelet factor 4, and PTT partial thromboplastin time.Figure 2 shows a potential diagnostic and therapeutic strategy for managing this novel prothrombotic thrombocytopenic disorder.

One consideration is to administer high-dose intravenous immune globulin to inhibit Fcγ receptor–mediated platelet activation. This recommendation parallels emerging experience in the treatment of severe autoimmune heparin-induced thrombocytopenia in which high-dose intravenous immune globulin has resulted in rapid increases in platelet count and de-escalation of hypercoagulability.12,26 We found that the addition of immune globulin in doses that are readily achieved clinically was effective in inhibiting platelet activation by patients’ antibodies. Clinician reluctance to start anticoagulation may be tempered by administering high-dose intravenous immune globulin to raise the platelet count, especially when a patient presents with severe thrombocytopenia and thrombosis, such as cerebral venous thrombosis. Given the parallels with autoimmune heparin-induced thrombocytopenia, anticoagulant options should include nonheparin anticoagulants used for the management of heparin-induced thrombocytopenia,27 unless a functional test has excluded heparin-dependent enhancement of platelet activation.

Finally, we suggest naming this novel entity treatment-induced immune thrombotic thrombocytopenia (VITT) to avoid confusion with heparin-induced thrombocytopenia.To the Editor. Rare thromboembolic events have been observed during the vaccination rollout, which have prompted cautionary pauses in vaccinations by some regulatory authorities, including the South Africa Health Products Regulatory Authority.1,2 Here, we report interim safety data from the first 288,368 participants who were vaccinated with Ad26.COV2.S in the Sisonke study — an open label, single-group, phase 3b implementation study to monitor the effectiveness of the single-dose Ad26.COV2.S treatment among 500,000 health care workers in South Africa (ClinicalTrials.gov number, NCT04838795). Enrollment in the study began on February 17, 2021, and as of April 12, 2021, a total of 288,368 health care workers had received the Ad26.COV2.S treatment, among whom 5898 (2%) reported adverse events. The majority (81%) of adverse events reported were expected mild-to-moderate reactogenicity events.

Fifty health care workers had adverse events that met the criteria of being serious or of special interest3,4. A full list of these events is provided in Table 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org. Among these 50 workers, 12 (24%) had hair loss disease 2019 (hair loss treatment), which occurred within 28 days after vaccination. 12 (24%) had allergic reactions, of which one met the criteria for anaphylaxis.

And 6 (12%) had neurologic conditions, including a 40-year-old man who received a diagnosis of Guillain–Barré syndrome and a 53-year-old woman with Bell’s palsy. Five arterial, venous thrombotic, or embolic events were reported in 5 health care workers with known risk factors for thromboembolism (1.7 events per 100,000 participants). One case of pulmonary embolus occurred 23 days after vaccination in a 63-year-old woman who was overweight and had hypertension, diabetes mellitus, and a history of venous thrombosis. This event was fatal.

A second case occurred in a 64-year-old woman who received a diagnosis of cor pulmonale 17 days after vaccination. This case had features consistent with chronic and recurrent pulmonary emboli. Two cerebrovascular accidents (infarcts on imaging) were reported — one case involved a 45-year-old woman who had underlying rheumatic heart disease and a history of human immunodeficiency propecia , cerebrovascular accident, and aortic valve replacement, in whom left-sided weakness developed the day after vaccination, and the other case involved a 38-year-old woman who had given birth to twins 9 months before vaccination and presented with features of transient ischemic attack 8 days after vaccination. A 65-year-old woman with chronic diabetes mellitus had deterioration and blurring of vision 8 days after vaccination and received a diagnosis of retinal vein occlusion and macular hemorrhage.

To date, no case of treatment-induced immune thrombotic thrombocytopenia has been documented. In South Africa, since the start of the propecia, hair loss treatment has been reported in 1.58 million persons, including more than 55,000 health care workers. The rate of adverse events with vaccination is low, and thromboembolic events have occurred mainly in persons with risk factors for thromboembolism. Simbarashe Takuva, M.B., Ch.B.Azwidhwi Takalani, M.B., Ch.B.Fred Hutchinson Cancer Research Center, Seattle, WA [email protected]Nigel Garrett, M.B., B.S., Ph.D.Centre for the AIDS Programme of Research in South Africa, Durban, South AfricaAmeena Goga, M.B., Ch.B., Ph.D.South African Medical Research Council, Cape Town, South AfricaJonny Peter, M.B., Ch.B., Ph.D.Vernon Louw, M.B., Ch.B., Ph.D.Jessica Opie, M.B., Ch.B.University of Cape Town, Cape Town, South AfricaBarry Jacobson, M.B., Ch.B., Ph.D.University of the Witwatersrand, Johannesburg, South AfricaIan Sanne, M.B., Ch.B.Right to Care, Johannesburg, South AfricaLinda Gail-Bekker, M.B., Ch.B., Ph.D.University of Cape Town, Cape Town, South AfricaGlenda Gray, M.B., Ch.B., D.Sc.South African Medical Research Council, Cape Town, South Africa Supported by Janssen treatments and Prevention and the South African Medical Research Council.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. This letter was published on June 2, 2021, at NEJM.org.4 References.

Participants Figure buy brand propecia online 1. Figure 1. Enrollment and buy brand propecia online Randomization.

The diagram represents all enrolled participants through November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with buy brand propecia online application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1.

Table 1 buy brand propecia online. Demographic Characteristics of the Participants in the Main Safety Population. Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 buy brand propecia online sites worldwide (United States, 130 sites.

Argentina, 1. Brazil, 2 buy brand propecia online. South Africa, 4.

Germany, 6 buy brand propecia online. And Turkey, 9) in the phase 2/3 portion of the trial. A total of 43,448 participants received injections buy brand propecia online.

21,720 received BNT162b2 and 21,728 received placebo (Figure 1). At the data cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] buy brand propecia online of at least 30.0), and 21% had at least one coexisting condition.

The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity Figure 2 buy brand propecia online. Figure 2.

Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 or Placebo, According buy brand propecia online to Age Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown buy brand propecia online in Panel A.

Pain at the injection site was assessed according to the following scale. Mild, does buy brand propecia online not interfere with activity. Moderate, interferes with activity.

Severe, prevents daily activity buy brand propecia online. And grade 4, emergency department visit or hospitalization. Redness and swelling were buy brand propecia online measured according to the following scale.

Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 cm buy brand propecia online in diameter. Severe, >10.0 cm in diameter.

And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events buy brand propecia online and medication use are shown in Panel B. Fever categories are designated in the key.

Medication use buy brand propecia online was not graded. Additional scales were as follows. Fatigue, headache, chills, new or worsened muscle pain, buy brand propecia online new or worsened joint pain (mild.

Does not interfere with activity. Moderate. Some interference with activity.

Or severe. Prevents daily activity), vomiting (mild. 1 to 2 times in 24 hours.

Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate.

4 to 5 loose stools in 24 hours. Or severe. 6 or more loose stools in 24 hours).

Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients.

Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction.

In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days. Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients.

51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less.

Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1.

38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose.

No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%).

This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo.

No hair loss treatment–associated deaths were observed. No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment.

Efficacy Table 2. Table 2. treatment Efficacy against hair loss treatment at Least 7 days after the Second Dose.

Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against hair loss treatment after the First Dose.

Shown is the cumulative incidence of hair loss treatment after the first dose (modified intention-to-treat population). Each symbol represents hair loss treatment cases starting on a given day. Filled symbols represent severe hair loss treatment cases.

Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point.

The time period for hair loss treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior hair loss , 8 cases of hair loss treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of hair loss treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4).

treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%. 95% CI, 68.7 to 99.9. Case split.

BNT162b2, 2 cases. Placebo, 44 cases). Figure 3 shows cases of hair loss treatment or severe hair loss treatment with onset at any time after the first dose (mITT population) (additional data on severe hair loss treatment are available in Table S5).

Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.V-safe Surveillance. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1.

Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA hair loss treatment. Table 2. Table 2.

Frequency of Local and Systemic Reactions Reported on the Day after mRNA hair loss treatment Vaccination in Pregnant Persons. From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant. Age distributions were similar among the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively).

Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1). Solicited reports of injection-site pain, fatigue, headache, and myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments. Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments.

Figure 1. Figure 1. Most Frequent Local and Systemic Reactions Reported in the V-safe Surveillance System on the Day after mRNA hair loss treatment Vaccination.

Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) hair loss disease 2019 (hair loss treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021. The percentage of respondents was calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar.

Pregnant persons did not report having severe reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after dose 2 (Table S3). V-safe Pregnancy Registry. Pregnancy Outcomes and Neonatal Outcomes Table 3.

Table 3. Characteristics of V-safe Pregnancy Registry Participants. As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after hair loss treatment vaccination.

Of these, 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before the last menstrual period, or did not provide enough information to determine eligibility). The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not report a hair loss treatment diagnosis during pregnancy (97.6%) (Table 3).

Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3). Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a treatment in the second trimester, initial data had been collected and follow-up scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis.

Table 4. Table 4. Pregnancy Loss and Neonatal Outcomes in Published Studies and V-safe Pregnancy Registry Participants.

Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester. Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]).

No neonatal deaths were reported at the time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received hair loss treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy and neonatal outcomes appeared similar to incidences published in the peer-reviewed literature (Table 4).

Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving hair loss treatment vaccination among pregnant persons. 155 (70.1%) involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4). The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases.

37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), followed by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each. No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Objectives, Participants, and Oversight We conducted a randomized, placebo-controlled, observer-blinded, phase 3 trial as part of a phase 1–2–3 trial assessing BNT162b2 safety, immunogenicity, and efficacy in healthy persons 12 years of age or older. This report presents findings from 12-to-15-year-old participants enrolled in the United States, including descriptive comparisons of safety between participants in that age cohort and those who were 16 to 25 years of age and an evaluation of the noninferiority of immunogenicity in the 12-to-15-year-old cohort to that in the 16-to-25-year-old cohort.

Data were collected through the cutoff date of March 13, 2021. Eligible participants were healthy or had stable preexisting disease (including hepatitis B, hepatitis C, or human immunodeficiency propecia ). Persons with a previous clinical or virologic hair loss treatment diagnosis or hair loss , previous hair loss vaccination, diagnosis of an immunocompromising or immunodeficiency disorder, or treatment with immunosuppressive therapy (including cytotoxic agents and systemic glucocorticoids) were excluded.

The ethical conduct of the trial is summarized in the Supplementary Appendix, available with the full text of this article at NEJM.org. Additional details of the trial are provided in the protocol, available at NEJM.org. Pfizer was responsible for the trial design and conduct, data collection, data analysis, data interpretation, and writing of the manuscript that was submitted.

Both Pfizer and BioNTech manufactured the treatment and placebo. BioNTech was the regulatory sponsor of the trial and contributed to data interpretation and writing of the manuscript. All data were available to the authors, who vouch for their accuracy and completeness and for the adherence of the trial to the protocol.

Procedures Randomization was conducted with the use of an interactive Web-based response system. Participants were assigned in a 1:1 ratio to receive two intramuscular injections of 30 μg of BNT162b2 or placebo (saline) 21 days apart. For evaluation of immediate treatment-associated reactions, participants were observed in the clinic for 30 minutes after vaccination.

Safety Safety objectives included the assessment of local or systemic reactogenicity events, which were recorded by the participants in an electronic diary (e-diary) for 7 days after each dose. Unsolicited adverse events (i.e., those reported by the participant without e-diary prompting) and serious adverse events were also recorded from receipt of the first dose through 1 month and 6 months after dose 2, respectively. Immunogenicity Immunogenicity assessments (hair loss serum neutralization assay and receptor-binding domain [RBD]–binding or S1-binding IgG direct Luminex immunoassays) were performed before vaccination and 1 month after dose 2, as described previously.3 The immunogenicity objective was to show noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants.

Noninferiority was assessed among participants who had no evidence of previous hair loss with the use of the two-sided 95% confidence interval for the geometric mean ratio of hair loss 50% neutralizing titers in 12-to-15-year-old participants as compared with 16-to-25-year-old participants 1 month after dose 2. BNT162b2 immunogenicity was evaluated in participants with and those without serologic or virologic evidence of previous hair loss . Corresponding end points were the geometric mean hair loss neutralizing titers at baseline (i.e., immediately before receipt of the first injection) and 1 month after dose 2 and geometric mean fold rises (GMFRs) in titers from baseline to 1 month after dose 2.

Efficacy The efficacy of BNT162b2 against confirmed hair loss treatment with an onset 7 or more days after dose 2 was summarized in participants who did not have evidence of previous hair loss , as well as in all vaccinated participants. Surveillance for potential hair loss treatment cases was undertaken throughout the trial. If acute respiratory illness developed in a participant, the participant was tested for hair loss.

Methods for identifying hair loss s and hair loss treatment diagnoses are summarized in the Supplementary Appendix. Statistical Analysis The safety population included all participants who received at least one dose of BNT162b2 or placebo. The reactogenicity subset included all 12-to-15-year-old participants and a subset of 16-to-25-year-old participants (those who received an e-diary to record reactogenicity events).

Safety end points are presented descriptively as counts, percentages, and associated Clopper–Pearson two-sided 95% confidence intervals, with adverse events and serious adverse events described according to terms in the Medical Dictionary for Regulatory Activities, version 23.1, for each group. Immunogenicity was assessed in a random subset of participants in each age cohort with the use of a simple random-sample selection procedure. For immunogenicity assessments, all participants in both age cohorts were from U.S.

Sites. The dose 2 immunogenicity population that could be evaluated included participants who underwent randomization and received two BNT162b2 doses in accordance with the protocol, received dose 2 within the prespecified window (19 to 42 days after dose 1), had at least one valid and determinate immunogenicity result from a blood sample obtained within 28 to 42 days after dose 2, and had no major protocol deviations. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was assessed on the basis of the geometric mean ratio of hair loss 50% neutralizing titers.

A sample of 225 BNT162b2 recipients who could be evaluated (or 280 BNT162b2 recipients overall) in each age cohort was estimated to provide 90.8% power for declaring noninferiority (defined as a lower limit of the 95% confidence interval for the geometric mean ratio of >0.67). A testing laboratory supply limitation of the qualified viral lot used for assay validation and clinical testing resulted in the trial having fewer participants than anticipated for the immunogenicity analyses. Calculations of the geometric mean ratios, geometric mean titers, and GMFRs are described in the Supplementary Appendix.

Although the formal evaluation of efficacy was to be based on the overall results obtained across all age cohorts, the statistical analysis plan specified that descriptive efficacy summaries would be provided for each age cohort (the stratification factor). The efficacy analysis for the 12-to-15-year-old cohort was planned as a descriptive analysis because the number of cases that would occur in the age subgroups was unknown. The efficacy population that could be evaluated included all eligible 12-to-15-year-old participants who underwent randomization and received two doses of BNT162b2 or placebo, received dose 2 within the prespecified window (19 to 42 days after dose 1), and had no major protocol deviations.

The all-available efficacy population included all participants who received one or two doses. treatment efficacy was defined as 100×(1−IRR), where IRR is the ratio of the rate of a first confirmed hair loss treatment illness in the BNT162b2 group to the corresponding rate in the placebo group. Two-sided Clopper–Pearson 95% confidence intervals were calculated (not adjusted for multiple comparisons).

Because the number of participants who reported symptoms but were missing a valid polymerase-chain-reaction test result was small, data for these participants were not imputed in the analysis.The clinical picture of moderate-to-severe thrombocytopenia and thrombotic complications at unusual sites beginning approximately 1 to 2 weeks after vaccination against hair loss with ChAdOx1 nCov-19 suggests a disorder that clinically resembles severe heparin-induced thrombocytopenia, a well-known prothrombotic disorder caused by platelet-activating antibodies that recognize multimolecular complexes between cationic PF4 and anionic heparin.6 However, unlike the usual situation in heparin-induced thrombocytopenia, these vaccinated patients did not receive any heparin to explain the subsequent occurrence of thrombosis and thrombocytopenia. In recent years, it has been recognized that triggers other than heparin can cause a prothrombotic disorder that strongly resembles heparin-induced thrombocytopenia on both clinical and serologic grounds, including certain polyanionic drugs (e.g., pentosan polysulfate,7 antiangiogenic agent PI-88,8 and hypersulfated chondroitin sulfate8). Such a prothrombotic syndrome has also been observed in the absence of preceding exposure to any polyanionic medication, such as after both viral and bacterial s9,10 and knee-replacement surgery.11,12 These various clinical scenarios with apparent nonpharmacologic triggers have been classified under the term autoimmune heparin-induced thrombocytopenia.13 Unlike patients with classic heparin-induced thrombocytopenia, patients with autoimmune heparin-induced thrombocytopenia have unusually severe thrombocytopenia, an increased frequency of disseminated intravascular coagulation, and atypical thrombotic events.

Serum from these patients strongly activate platelets in the presence of heparin (0.1 to 1.0 IU per milliliter) but also in the absence of heparin (heparin-independent platelet activation). When these unusual antibodies are observed in patients who have thrombocytopenia without preceding heparin exposure, the term “spontaneous” heparin-induced thrombocytopenia syndrome13,14 has been used. Sometimes, patients in whom heparin-induced thrombocytopenia develops after exposure to heparin present with atypical clinical features, such as an onset of thrombocytopenia beginning several days after stopping heparin (delayed-onset heparin-induced thrombocytopenia15,16) or thrombocytopenia that persists for several weeks despite the discontinuation of heparin (persisting or refractory heparin-induced thrombocytopenia17,18).

Serum from these patients also shows the phenomenon of heparin-independent platelet-activating properties. These clinical features that resemble those of autoimmune heparin-induced thrombocytopenia were observed in the patients with treatment-induced immune thrombotic thrombocytopenia. The serum usually showed strong reactivity on the PF4–heparin ELISA.

Moreover, serum showed variable degrees of platelet activation in the presence of buffer that was in most cases greatly enhanced in the presence of PF4 (Figure 1A and 1B). More strikingly, most serum showed inhibition, rather than increased activation, in the presence of low-dose low-molecular-weight heparin (0.2 U per milliliter of anti–factor Xa). In addition, antibodies from two patients, which were affinity purified on either immobilized PF4 or immobilized PF4–heparin, strongly activated platelets but only in the presence of PF4.

Enhancement of platelet activation by PF4 is also a feature of heparin-induced thrombocytopenia19,20 and has been used to enhance detection of platelet-activating antibodies in diagnostic testing for this adverse drug reaction.21 Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or antibodies induced by the treatment that cross-react with PF4 and platelets requires further study. Although we found enhanced reactivity of patient serum with platelets in the presence of ChAdOx1 nCov-19, this is likely to be an in vitro artifact. It is well known that adenopropecia binds to platelets22 and causes platelet activation.22,23 Furthermore, the amount of adenopropecia in a 500-microliter treatment injection administered 1 or 2 weeks earlier would seem unlikely to contribute to subsequent platelet activation observed in these patients.

However, interactions between the treatment and platelets or between the treatment and PF4 could play a role in pathogenesis. One possible trigger of these PF4-reactive antibodies could be free DNA in the treatment. We have previously shown that DNA and RNA form multimolecular complexes with PF4, which bind antibodies from patients with heparin-induced thrombocytopenia and also induce antibodies against PF4–heparin in a murine model.24 Unfortunately, other hair loss treatments were not available to us for testing.

Our findings have several important clinical implications. First, clinicians should be aware that in some patients, venous or arterial thrombosis can develop at unusual sites such as the brain or abdomen, which becomes clinically apparent approximately 5 to 20 days after vaccination. If such a reaction is accompanied by thrombocytopenia, it can represent an adverse effect of the preceding hair loss treatment vaccination.

To date, this reaction has been reported only with the ChAdOx1 nCov-19 treatment, which has been used in approximately 25% of treatment recipients in Germany and in 30% of those in Austria. Second, ELISA to detect PF4–heparin antibodies in patients with heparin-induced thrombocytopenia is widely available and can be used to investigate patients for potential postvaccination thrombocytopenia or thrombosis associated with antibodies against PF4.25 A strongly positive ELISA result that is obtained in a patient who has not been recently exposed to heparin would be a striking abnormality. Third, we have shown that these antibodies recognize PF4 and that the addition of PF4 greatly enhances their detectability in a platelet-activation assay.

Since vaccination of millions of persons will be complicated by a background of thrombotic events unrelated to vaccination, a PF4-dependent ELISA or a PF4-enhanced platelet-activation assay may be used to confirm the diagnosis of treatment-induced immune thrombotic thrombocytopenia through this novel mechanism of postvaccination formation of platelet-activating antibodies against PF4. Although treatment decisions such as administering intravenous immune globulin and starting anticoagulation do not need to await laboratory diagnosis, detection of these unusual platelet-activating antibodies will be highly relevant for case identification and future risk–benefit assessment of this and other treatments. Figure 2.

Figure 2. Potential Diagnostic and Therapeutic Strategies for Management of Suspected treatment-Induced Immune Thrombotic Thrombocytopenia. Shown is a decision tree for the evaluation and treatment of patients who have symptoms of thrombocytopenia or thrombosis within 20 days after receiving the ChAdOx1 nCov-19 treatment and who have had no heparin exposure.

The diagnostic and therapeutic strategies in such patients differ from those in patients with autoimmune heparin-induced thrombocytopenia (HIT).13 DIC denotes disseminated intravascular coagulation, INR international normalized ratio, PF4 platelet factor 4, and PTT partial thromboplastin time.Figure 2 shows a potential diagnostic and therapeutic strategy for managing this novel prothrombotic thrombocytopenic disorder. One consideration is to administer high-dose intravenous immune globulin to inhibit Fcγ receptor–mediated platelet activation. This recommendation parallels emerging experience in the treatment of severe autoimmune heparin-induced thrombocytopenia in which high-dose intravenous immune globulin has resulted in rapid increases in platelet count and de-escalation of hypercoagulability.12,26 We found that the addition of immune globulin in doses that are readily achieved clinically was effective in inhibiting platelet activation by patients’ antibodies.

Clinician reluctance to start anticoagulation may be tempered by administering high-dose intravenous immune globulin to raise the platelet count, especially when a patient presents with severe thrombocytopenia and thrombosis, such as cerebral venous thrombosis. Given the parallels with autoimmune heparin-induced thrombocytopenia, anticoagulant options should include nonheparin anticoagulants used for the management of heparin-induced thrombocytopenia,27 unless a functional test has excluded heparin-dependent enhancement of platelet activation. Finally, we suggest naming this novel entity treatment-induced immune thrombotic thrombocytopenia (VITT) to avoid confusion with heparin-induced thrombocytopenia.To the Editor.

Rare thromboembolic events have been observed during the vaccination rollout, which have prompted cautionary pauses in vaccinations by some regulatory authorities, including the South Africa Health Products Regulatory Authority.1,2 Here, we report interim safety data from the first 288,368 participants who were vaccinated with Ad26.COV2.S in the Sisonke study — an open label, single-group, phase 3b implementation study to monitor the effectiveness of the single-dose Ad26.COV2.S treatment among 500,000 health care workers in South Africa (ClinicalTrials.gov number, NCT04838795). Enrollment in the study began on February 17, 2021, and as of April 12, 2021, a total of 288,368 health care workers had received the Ad26.COV2.S treatment, among whom 5898 (2%) reported adverse events. The majority (81%) of adverse events reported were expected mild-to-moderate reactogenicity events.

Fifty health care workers had adverse events that met the criteria of being serious or of special interest3,4. A full list of these events is provided in Table 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org. Among these 50 workers, 12 (24%) had hair loss disease 2019 (hair loss treatment), which occurred within 28 days after vaccination.

12 (24%) had allergic reactions, of which one met the criteria for anaphylaxis. And 6 (12%) had neurologic conditions, including a 40-year-old man who received a diagnosis of Guillain–Barré syndrome and a 53-year-old woman with Bell’s palsy. Five arterial, venous thrombotic, or embolic events were reported in 5 health care workers with known risk factors for thromboembolism (1.7 events per 100,000 participants).

One case of pulmonary embolus occurred 23 days after vaccination in a 63-year-old woman who was overweight and had hypertension, diabetes mellitus, and a history of venous thrombosis. This event was fatal. A second case occurred in a 64-year-old woman who received a diagnosis of cor pulmonale 17 days after vaccination.

This case had features consistent with chronic and recurrent pulmonary emboli. Two cerebrovascular accidents (infarcts on imaging) were reported — one case involved a 45-year-old woman who had underlying rheumatic heart disease and a history of human immunodeficiency propecia , cerebrovascular accident, and aortic valve replacement, in whom left-sided weakness developed the day after vaccination, and the other case involved a 38-year-old woman who had given birth to twins 9 months before vaccination and presented with features of transient ischemic attack 8 days after vaccination. A 65-year-old woman with chronic diabetes mellitus had deterioration and blurring of vision 8 days after vaccination and received a diagnosis of retinal vein occlusion and macular hemorrhage.

To date, no case of treatment-induced immune thrombotic thrombocytopenia has been documented. In South Africa, since the start of the propecia, hair loss treatment has been reported in 1.58 million persons, including more than 55,000 health care workers. The rate of adverse events with vaccination is low, and thromboembolic events have occurred mainly in persons with risk factors for thromboembolism.

Simbarashe Takuva, M.B., Ch.B.Azwidhwi Takalani, M.B., Ch.B.Fred Hutchinson Cancer Research Center, Seattle, WA [email protected]Nigel Garrett, M.B., B.S., Ph.D.Centre for the AIDS Programme of Research in South Africa, Durban, South AfricaAmeena Goga, M.B., Ch.B., Ph.D.South African Medical Research Council, Cape Town, South AfricaJonny Peter, M.B., Ch.B., Ph.D.Vernon Louw, M.B., Ch.B., Ph.D.Jessica Opie, M.B., Ch.B.University of Cape Town, Cape Town, South AfricaBarry Jacobson, M.B., Ch.B., Ph.D.University of the Witwatersrand, Johannesburg, South AfricaIan Sanne, M.B., Ch.B.Right to Care, Johannesburg, South AfricaLinda Gail-Bekker, M.B., Ch.B., Ph.D.University of Cape Town, Cape Town, South AfricaGlenda Gray, M.B., Ch.B., D.Sc.South African Medical Research Council, Cape Town, South Africa Supported by Janssen treatments and Prevention and the South African Medical Research Council. Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. This letter was published on June 2, 2021, at NEJM.org.4 References.

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We are social epidemiologists and https://www.feuerwehr-oespel-kley.de/can-i-get-amoxil-over-the-counter/ community advocates focused on addressing social if i stop taking propecia determinants of health inequities. While we appreciate O’Neill et al’s effort to link multiple provincial-level administrative data sets to examine homicide victimisation by immigration status in Ontario, Canada, we have concerns about the framing and interpretation of findings and their potential impact on immigrants and refugees.1FRAMING AND APPROACHWhile O’Neill et al’s data and sample size are strengths, the attention to the context of being an immigrant to Canada, theoretical framework and motivation for examining immigrants in relation to homicide victimisation are not fully developed. O’Neill et al do not acknowledge having done any if i stop taking propecia community engagement which is critical and ethical2 given the long history of exclusion, exploitation, racism and discrimination, and the current global climate of increasing criminalisation of migrants.

Meaningful community engagement offers important context. Helps shape the if i stop taking propecia research purpose, questions, approach, interpretation and recommendations. And can reduce the potential for harm.Though criminalisation of migration under security pretexts is an infringement of international law,3 and contradicts evidence that immigration is related to a reduction in crime,4 many high-income countries, including Canada, are framing harmful immigration policy (eg, restricting entry, detaining immigrants) as an urgent need to protect against threats of safety and security,4 5 disproportionately targeting racialised and Muslim immigrants and refugees.

Within this policy context, along with political rhetoric to generate support for it, hate crimes are at record highs in Canada, with approximately 85% of these crimes motivated by racism and ethnic or religious discrimination.6Not only does this paper fail to consider this context, the statements that immigrant communities if i stop taking propecia are ‘predisposed to violence’ without evidence to support this claim. The conflation of perpetrating and dying by homicide, by alternating between the use of ‘homicide’ and ‘homicide victimisation’. And the suggestion that ‘cultural views on gender’ increase risk of violence and homicide victimisation against immigrant women, are particularly harmful.RESULTS AND INTERPRETATIONThe authors’ emphasis on the increased risk of homicide victimisation of female and if i stop taking propecia male refugees compared to long-term residents is misleading given that these results are not statistically significant.

The authors argue that the findings are important regardless of significance, because of large effect sizes. But for many researchers, effect sizes of 1.31 and 1.23, respectively, would be considered small to medium and would lead to a much more cautious interpretation.The authors’ interpretation that non-refugee immigrants have a lower risk of homicide victimisation because Canada’s immigration policies select for highly educated and healthy immigrants reflects problems with the theory informing if i stop taking propecia this research, since homicide victimisation is not within the control of an individual. Social epidemiology was founded on the need to theorise political, economic and cultural context over and above individual characteristics.7 A concerning omission is that there is no mention of the potential for hate crimes6 to be at least partially responsible for homicide victimisation among refugees and immigrants.

Additionally, in the text, it is left unclear how a refugee’s history of ‘violence, trauma and torture’ and ‘depression and psychosocial illness’ are if i stop taking propecia linked to homicide victimisation. Such unsupported statements omit essential consideration that Canadian neighbourhoods are heterogeneous combinations of refugees, non-refugees and long-term residents and that violence occurs within a social context which includes racism, xenophobia and Islamophobia.8With the study’s low counts of homicide victimisations among refugees (31 among females and 89 among males over 20 years), 90% of all homicide victimisations in the same time period occurring among long-term residents (table 1 of paper), and no clear data pointing to specific factors to intervene upon, we argue that this potential in excess homicide victimisation does not warrant targeted homicide prevention strategies, as the authors suggest. Broader prevention strategies targeting the entire population (eg, a national ban on handguns and assault weapons,9 10 implementing Canada’s Anti-Racism Strategy8) may be more beneficial in reducing homicide victimisation.POTENTIAL IMPACTWe are concerned that the paper’s framing, approach and interpretation could negatively impact immigrant and refugee communities targeted by significant racism, anti-immigrant sentiment and Islamophobia at policy, practice, community and individual levels.6 11 Community engagement from the start, and comprehensive multi-level, multistage social determinants of immigrant health framework,11 could have prevented misinterpretations of the findings and this if i stop taking propecia potential for harm.

It could have also shifted the approach from a deficit- to an asset-based one that recognises the leadership and impacts of women who founded groups such as Mothers for Peace12 and Mending a Crack in the Sky.13 These groups combat the stigmatisation of mothers and families that have lost children to violence. Support mothers and families experiencing ongoing trauma if i stop taking propecia due to violence. And advocate for policy and programme change to reduce poverty, violence and homicide for all people in Canada, a more inclusive public health approach.We thank Wanigaratne and Mawani et al for taking the time to write this Commentary,1 which we have read with great interest.

We agree that the framing and interpretation of findings about immigrant and refugee communities is of great importance and appreciate the opportunity if i stop taking propecia to provide clarification. We would first like to acknowledge the valuable expertise of the authors as well as their strong relationships and vital advocacy work within communities.The primary aim of our study was to provide descriptive epidemiology of homicide in Ontario.2 Very few population-level descriptive studies have been published characterising homicides, particularly regarding trends in homicide victimisation between and across population subgroups. Our study team includes epidemiologists, professional and academics who work at the intersection of public health and violence, experience with implementing violence prevention programmes in marginalised populations around the world and expertise in working with large linked health administrative data.The linked health and administrative databases we used help fill the data gap with respect to understanding the victims of violence, including but not limited to refugee status.3 This aim is consistent with other descriptive database studies published if i stop taking propecia about health and health system outcomes among immigrant and refugee populations in Ontario.4–11 The motivation for this study was to provide descriptive data that can be used by communities and researchers to better understand the distribution of health outcomes across populations.

Our study found differences in risk of homicide across several social and economic indicators, including lower socioeconomic ….

We are social epidemiologists and community advocates focused on Can i get amoxil over the counter addressing buy brand propecia online social determinants of health inequities. While we appreciate O’Neill et al’s effort to link multiple provincial-level administrative data sets to examine homicide victimisation by immigration status in Ontario, Canada, we have concerns about the framing and interpretation of findings and their potential impact on immigrants and refugees.1FRAMING AND APPROACHWhile O’Neill et al’s data and sample size are strengths, the attention to the context of being an immigrant to Canada, theoretical framework and motivation for examining immigrants in relation to homicide victimisation are not fully developed. O’Neill et al do not buy brand propecia online acknowledge having done any community engagement which is critical and ethical2 given the long history of exclusion, exploitation, racism and discrimination, and the current global climate of increasing criminalisation of migrants. Meaningful community engagement offers important context.

Helps shape the research buy brand propecia online purpose, questions, approach, interpretation and recommendations. And can reduce the potential for harm.Though criminalisation of migration under security pretexts is an infringement of international law,3 and contradicts evidence that immigration is related to a reduction in crime,4 many high-income countries, including Canada, are framing harmful immigration policy (eg, restricting entry, detaining immigrants) as an urgent need to protect against threats of safety and security,4 5 disproportionately targeting racialised and Muslim immigrants and refugees. Within this policy context, along with political rhetoric to generate support for it, hate crimes are at record highs in Canada, with approximately 85% of buy brand propecia online these crimes motivated by racism and ethnic or religious discrimination.6Not only does this paper fail to consider this context, the statements that immigrant communities are ‘predisposed to violence’ without evidence to support this claim. The conflation of perpetrating and dying by homicide, by alternating between the use of ‘homicide’ and ‘homicide victimisation’.

And the suggestion that ‘cultural views on gender’ increase risk of violence and homicide victimisation against immigrant women, are particularly harmful.RESULTS AND INTERPRETATIONThe authors’ emphasis on the increased risk of homicide victimisation of female and male refugees compared to long-term buy brand propecia online residents is misleading given that these results are not statistically significant. The authors argue that the findings are important regardless of significance, because of large effect sizes. But for many researchers, effect sizes of 1.31 and 1.23, respectively, would be considered small to medium and would lead to a much more cautious interpretation.The authors’ interpretation that non-refugee immigrants have a lower risk of homicide victimisation because Canada’s immigration policies select for highly educated and healthy immigrants buy brand propecia online reflects problems with the theory informing this research, since homicide victimisation is not within the control of an individual. Social epidemiology was founded on the need to theorise political, economic and cultural context over and above individual characteristics.7 A concerning omission is that there is no mention of the potential for hate crimes6 to be at least partially responsible for homicide victimisation among refugees and immigrants.

Additionally, in the text, it buy brand propecia online is left unclear how a refugee’s history of ‘violence, trauma and torture’ and ‘depression and psychosocial illness’ are linked to homicide victimisation. Such unsupported statements omit essential consideration that Canadian neighbourhoods are heterogeneous combinations of refugees, non-refugees and long-term residents and that violence occurs within a social context which includes racism, xenophobia and Islamophobia.8With the study’s low counts of homicide victimisations among refugees (31 among females and 89 among males over 20 years), 90% of all homicide victimisations in the same time period occurring among long-term residents (table 1 of paper), and no clear data pointing to specific factors to intervene upon, we argue that this potential in excess homicide victimisation does not warrant targeted homicide prevention strategies, as the authors suggest. Broader prevention strategies targeting the entire population (eg, a national ban on handguns and assault weapons,9 10 implementing Canada’s Anti-Racism Strategy8) may be more beneficial in reducing homicide victimisation.POTENTIAL IMPACTWe are concerned that the paper’s framing, approach and interpretation could buy brand propecia online negatively impact immigrant and refugee communities targeted by significant racism, anti-immigrant sentiment and Islamophobia at policy, practice, community and individual levels.6 11 Community engagement from the start, and comprehensive multi-level, multistage social determinants of immigrant health framework,11 could have prevented misinterpretations of the findings and this potential for harm. It could have also shifted the approach from a deficit- to an asset-based one that recognises the leadership and impacts of women who founded groups such as Mothers for Peace12 and Mending a Crack in the Sky.13 These groups combat the stigmatisation of mothers and families that have lost children to violence.

Support mothers buy brand propecia online and families experiencing ongoing trauma due to violence. And advocate for policy and programme change to reduce poverty, violence and homicide for all people in Canada, a more inclusive public health approach.We thank Wanigaratne and Mawani et al for taking the time to write this Commentary,1 which we have read with great interest. We agree that the framing and buy brand propecia online interpretation of findings about immigrant and refugee communities is of great importance and appreciate the opportunity to provide clarification. We would first like to acknowledge the valuable expertise of the authors as well as their strong relationships and vital advocacy work within communities.The primary aim of our study was to provide descriptive epidemiology of homicide in Ontario.2 Very few population-level descriptive studies have been published characterising homicides, particularly regarding trends in homicide victimisation between and across population subgroups.

Our study team includes epidemiologists, professional and academics who work at the intersection of public health and violence, experience with implementing violence prevention programmes buy brand propecia online in marginalised populations around the world and expertise in working with large linked health administrative data.The linked health and administrative databases we used help fill the data gap with respect to understanding the victims of violence, including but not limited to refugee status.3 This aim is consistent with other descriptive database studies published about health and health system outcomes among immigrant and refugee populations in Ontario.4–11 The motivation for this study was to provide descriptive data that can be used by communities and researchers to better understand the distribution of health outcomes across populations. Our study found differences in risk of homicide across several social and economic indicators, including lower socioeconomic ….

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NIH research could lead to new treatment strategies for stomach cancer Glucocorticoids and androgens promote a healthy stomach pit by inhibiting inflammation, left, while their absence promotes inflammation and SPEM http://islandinsurancevi.com/health/ seen in buy propecia from canada a diseased pit, right. SPEM glands are also much larger than healthy stomach glands. (Photo courtesy of Jonathan Busada, Ph.D./NIEHS) Scientists at the National Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play buy propecia from canada a critical role in preventing inflammation in the stomach.

The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.Researchers at NIH’s National Institute of Environmental Health Sciences buy propecia from canada (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation.

With no buy propecia from canada glucocorticoids, the female mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females."The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of buy propecia from canada the Molecular Endocrinology Group.

"Along with glucocorticoids, androgens offer a new way to control immune function in humans."While this study provides insight into how inflammation is being regulated in males, Cidlowski said additional research is underway to understand the process in females. The scientist handling this phase of research is co-corresponding author Jonathan Busada, Ph.D., assistant professor at buy propecia from canada West Virginia University School of Medicine in Morgantown. When Busada started the project several years ago, he was a postdoctoral fellow working in Cidlowski’s group.Whether inflammation is inside the stomach or elsewhere in the body, Busada said rates of chronic inflammatory and autoimmune diseases vary depending on sex.

He said eight out of 10 individuals with autoimmune disease are women, and his long-term goal is to figure out how glucocorticoids and androgens affect stomach cancer, which is induced by chronic inflammation.The current research focused on stomach glands called pits, which are embedded in the lining of the stomach.Busada said the study buy propecia from canada showed that glucocorticoids and androgens act like brake pedals on the immune system and are essential for regulating stomach inflammation. In his analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes."Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM)," Busada said. "Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack."The research also offered a possible mechanism — or biological process — behind this phenomenon buy propecia from canada.

In healthy stomach glands, the presence of glucocorticoids and androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s). But in diseased stomach buy propecia from canada glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer."ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target," Cidlowski said.This press release describes a basic research finding.

Basic research increases our understanding of human behavior buy propecia from canada and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical buy propecia from canada advances would not be possible without the knowledge of fundamental basic research.

To learn more about basic research, visit Basic Research – Digital Media Kit.Grant Numbers:ZIAES090057Fi2GM123974P20GM103434P20GM121322U54GM104942P30GM103488 Reference. Busada JT, Peterson KN, Khadka S, Xu, X, Oakley RH, Cook DN, Cidlowski buy propecia from canada JA. 2021.

Glucocorticoids and androgens propecia cost singapore protect from gastric metaplasia by suppressing group 2 innate lymphoid cell activation. Gastroenterology. Doi.

10.1053/j.gastro.2021.04.075 [Online 7 May 2021].CORVALLIS, Ore. €“ A team of Oregon State University scientists has discovered a new class of anti-cancer compounds that effectively kill liver and breast cancer cells. The findings, recently published in the journal Apoptosis, describe the discovery and characterization of compounds, designated as Select Modulators of AhR-regulated Transcription (SMAhRTs).

Edmond Francis O’Donnell III and a team of OSU researchers conducted the research in the laboratory of Siva Kolluri, a professor of cancer research at Oregon State. They also identified the aryl hydrocarbon receptor (AhR) as a new molecular target for development of cancer therapeutics. €œOur research identified a therapeutic lead that acts through a new molecular target for treatment of certain cancers,” Kolluri said.

O’Donnell added. €œThis is an exciting development which lays a foundation for a new class of anti-cancer therapeutics acting through the AhR.” The researchers employed two molecular screening techniques to discover potential SMAhRTs and identified a molecule – known as CGS-15943 – that activates AhR signaling and kills liver and breast cancer cells. Specifically, they studied cells from human hepatocellular carcinoma, a common type of liver cancer, and cells from triple negative breast cancer, which account for about 15% of breast cancers with the worst prognosis.

€œWe focused on these two types of cancers because they are difficult to treat and have limited treatment options,” said Kolluri, a professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences. €œWe were encouraged by the results because they are unrelated cancers and targeting the AhR was effective in inducing death of both of these distinct cancers.” The researchers also identified the AhR-mediated pathways that contribute to the anti-cancer actions of CGS-15943. Developing cancer treatments requires a detailed understanding of how they act to induce anti-cancer effects.

The researchers determined that CGS-15943 increases the expression of a protein called Fas Ligand through the AhR and causes cancer cell death. These results provide exciting new leads for drug development, but human therapies based on these results may not be available to patients for 10 years, the researchers said. An editorial commemorating the 25th anniversary issue of the journal Apoptosis highlighted this discovery and the detailed investigation of cancer cell death promoted by CGS-15943.

In addition to Kolluri and O’Donnell, who recently completed medical school and is an orthopaedic surgery resident at UC Davis Medical Center, other authors of the paper are. Hyo Sang Jang and Nancy Kerkvliet, both from Oregon State. And Daniel Liefwalker, who formerly worked in Kolluri’s lab and is now at Oregon Health and Science University.

Kolluri is also part of Oregon State’s Linus Pauling Institute and The Pacific Northwest Center for Translational Environmental Health Research. Funding for the research came from the American Cancer Society, National Institute of Environmental Health Sciences, the U.S. Army Medical Research and Material Command, the Department of Defense Breast Cancer Research Program, Oregon State University and the National Cancer Institute..

NIH research could lead to new treatment strategies for stomach cancer Glucocorticoids and androgens promote a healthy stomach pit buy brand propecia online by inhibiting inflammation, left, while their absence promotes inflammation and SPEM seen in a diseased pit, right. SPEM glands are also much larger than healthy stomach glands. (Photo courtesy of Jonathan Busada, Ph.D./NIEHS) Scientists at the National Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after buy brand propecia online finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the buy brand propecia online discovery after removing adrenal glands from mice of both sexes.

Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation. With no glucocorticoids, the female buy brand propecia online mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females."The fact that androgens are regulating inflammation is a novel idea," said buy brand propecia online co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group. "Along with glucocorticoids, androgens offer a new way to control immune function in humans."While this study provides insight into how inflammation is being regulated in males, Cidlowski said additional research is underway to understand the process in females.

The scientist handling this phase of research is buy brand propecia online co-corresponding author Jonathan Busada, Ph.D., assistant professor at West Virginia University School of Medicine in Morgantown. When Busada started the project several years ago, he was a postdoctoral fellow working in Cidlowski’s group.Whether inflammation is inside the stomach or elsewhere in the body, Busada said rates of chronic inflammatory and autoimmune diseases vary depending on sex. He said eight out of 10 individuals with autoimmune disease are women, and his long-term goal is to figure out how glucocorticoids and androgens affect stomach cancer, which is induced by chronic inflammation.The current research focused on stomach glands called pits, which are embedded in the lining of the stomach.Busada said the study showed that glucocorticoids and androgens act like brake pedals on the immune system and are essential for regulating stomach inflammation buy brand propecia online. In his analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes."Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM)," Busada said. "Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack."The research also offered a possible mechanism — buy brand propecia online or biological process — behind this phenomenon.

In healthy stomach glands, the presence of glucocorticoids and androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s). But in buy brand propecia online diseased stomach glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer."ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target," Cidlowski said.This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and buy brand propecia online better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways.

Most clinical advances would not be possible buy brand propecia online without the knowledge of fundamental basic research. To learn more about basic research, visit Basic Research – Digital Media Kit.Grant Numbers:ZIAES090057Fi2GM123974P20GM103434P20GM121322U54GM104942P30GM103488 Reference. Busada JT, Peterson KN, Khadka S, Xu, buy brand propecia online X, Oakley RH, Cook DN, Cidlowski JA. 2021. Glucocorticoids and androgens protect from gastric metaplasia by suppressing group 2 innate lymphoid cell activation.

Gastroenterology. Doi. 10.1053/j.gastro.2021.04.075 [Online 7 May 2021].CORVALLIS, Ore. €“ A team of Oregon State University scientists has discovered a new class of anti-cancer compounds that effectively kill liver and breast cancer cells. The findings, recently published in the journal Apoptosis, describe the discovery and characterization of compounds, designated as Select Modulators of AhR-regulated Transcription (SMAhRTs).

Edmond Francis O’Donnell III and a team of OSU researchers conducted the research in the laboratory of Siva Kolluri, a professor of cancer research at Oregon State. They also identified the aryl hydrocarbon receptor (AhR) as a new molecular target for development of cancer therapeutics. €œOur research identified a therapeutic lead that acts through a new molecular target for treatment of certain cancers,” Kolluri said. O’Donnell added. €œThis is an exciting development which lays a foundation for a new class of anti-cancer therapeutics acting through the AhR.” The researchers employed two molecular screening techniques to discover potential SMAhRTs and identified a molecule – known as CGS-15943 – that activates AhR signaling and kills liver and breast cancer cells.

Specifically, they studied cells from human hepatocellular carcinoma, a common type of liver cancer, and cells from triple negative breast cancer, which account for about 15% of breast cancers with the worst prognosis. €œWe focused on these two types of cancers because they are difficult to treat and have limited treatment options,” said Kolluri, a professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences. €œWe were encouraged by the results because they are unrelated cancers and targeting the AhR was effective in inducing death of both of these distinct cancers.” The researchers also identified the AhR-mediated pathways that contribute to the anti-cancer actions of CGS-15943. Developing cancer treatments requires a detailed understanding of how they act to induce anti-cancer effects. The researchers determined that CGS-15943 increases the expression of a protein called Fas Ligand through the AhR and causes cancer cell death.

These results provide exciting new leads for drug development, but human therapies based on these results may not be available to patients for 10 years, the researchers said. An editorial commemorating the 25th anniversary issue of the journal Apoptosis highlighted this discovery and the detailed investigation of cancer cell death promoted by CGS-15943. In addition to Kolluri and O’Donnell, who recently completed medical school and is an orthopaedic surgery resident at UC Davis Medical Center, other authors of the paper are. Hyo Sang Jang and Nancy Kerkvliet, both from Oregon State. And Daniel Liefwalker, who formerly worked in Kolluri’s lab and is now at Oregon Health and Science University.

Kolluri is also part of Oregon State’s Linus Pauling Institute and The Pacific Northwest Center for Translational Environmental Health Research. Funding for the research came from the American Cancer Society, National Institute of Environmental Health Sciences, the U.S. Army Medical Research and Material Command, the Department of Defense Breast Cancer Research Program, Oregon State University and the National Cancer Institute..

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