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Since the global youth movement, 1+1 youth Initiative was launched on World TB Day 2019, flagyl for bv followed by the adoption of flagyl online in canada the Youth Declaration to End TB at the first-ever Global Youth Townhall on ending TB, there has been significant progress over the past year. The 1+1 Initiative has expanded to include thousands of youth across the world in countries like Bangladesh, Nepal, India, Indonesia, Philippines, and Vietnam.The social media platforms set up as part of the 1+1 youth initiative are joined and followed by more than 15000 young people including WHO End TB forum. Similarly, Global TB Programme has flagyl online in canada established #Youth2EndTB Global Youth Network where more than 1800 youths from 95+ countries have already joined. Besides, in order to recognise the youth efforts and encourage youth engagement on ending TB, youth story series was conducted.Moreover, 50 and more different youth-led activities and virtual events on ending TB have been conducted worldwide.

This includes sensitizing young people, peer education trainings flagyl online in canada in schools and universities,and encouraging them to become TB advocates, and supporting TB patients in the community with resources, advice, and encouragement. In addition, we are enthusiastic about cross country youth dialogue series that have been started where youths from different countries can participate and learn from each other.For instance, one of the inspiring examples is that of Nepal, young people in this country have established national and provincial youth networks to help young people, through capacity building and in ensuring their participation in policy making and community level awareness building programmes. Likewise, in March 2020, Vietnam National Tuberculosis program launched National Youth Movement against TB which aims on reaching 10 million young people as well as educating all primary school students with TB knowledge and good practices on combating TB and lung diseases.Another exciting flagyl online in canada example is from Indonesia. Their national youth movement against TB has been conducting Art exhibitions as well as creating TB awareness through social media campaign.Furthermore, WHO Global TB Program is currently developing training manual targeting End TB youth leaders, young survivors, and young health professionals.

It will be available at End TB channel of Open WHO platform after completing it's six regional youth flagyl online in canada consultations.The Behavioural Insights Unit of the WHO released a meeting report of the Technical Advisory Group (TAG) on the special session on acceptance and uptake of buy antibiotics treatments, held on 15 October 2020. The meeting report outlines the factors that drive people’s behaviour in relation to treatment acceptance and uptake. An enabling environment, social influences flagyl online in canada and motivation. The image above is a visual narration that captures highlights of the meeting on 15 October 2020, during which the TAG on Behavioural Insights and Sciences for Health discussed behavioural considerations in relation to buy antibiotics treatment acceptance and uptake.

The discussion was structured around three key questions..

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Yes
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24h
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Former Editor-in-Chief of the Postgraduate http://www.em-tilleuls-souffelweyersheim.ac-strasbourg.fr/?slideshow=rentree2016 Medical Journal Dr Barry Ian Hoffbrand died suddenly on April 24, 2020 at the age of 86.A prominent member of a generation of very bright young doctors at University flagyl giardia College Hospital (UCH) in London who went on to distinguished careers, he was much admired for his keen intellect, clinical perception and skills, gentle good humour and kindly nature, combined with a wonderfully sharp intelligence. Professor Dame Jane Dacre remembered him as ‘a kind, witty, clever man, and a great physician’.He was born in Bradford, West Yorkshire, to Philip Hoffbrand, a bespoke tailor, and Minnie (née Freedman), both from Jewish families from Eastern Europe. After Bradford Grammar School, he went up to read medicine from 1952 to 1956 at The Queen’s College, Oxford, where he was a keen member of the college cricket flagyl giardia team—the Quondams. He was pleased to feature in the 1950s on the silver Quondams Cup. Clinical training on a Goldsmid scholarship followed from 1956 to 1958 at UCH Medical School, London, where he was awarded prizes in clinical pathology and haematology.

His postgraduate medical training was flagyl giardia mainly at UCH, where he was house physician to Max (later Lord) Rosenheim, after an initial 6 months at St Luke’s Hospital, Bradford. He also spent a year as senior research fellow from 1967 to 1968 at the Cardiovascular Research Institute, at the University of California Medical Center in San Francisco. Barry’s research on cardiovascular physiology lead to a DM in 1971 from Oxford University.Barry was appointed in 1970 as a consultant physician at the Whittington Hospital and honorary senior clinical lecturer at UCH Medical School, with interests in general and …INTRODUCTIONAs cardiac arrest occurs in around 20% of the patients with severe buy antibiotics, a large number of them will require immediate resuscitative efforts.1 Cardiopulmonary resuscitation (CPR) in buy antibiotics flagyl has become a source of speculation and debate worldwide. Healthcare professionals (HCPs) resuscitating this subset of patients are subject to fears and enormous mental stress pertaining to risk of transmission, breach in personal protective equipment (PPE), unsure effectiveness of PPE and nevertheless bleak positive outcomes in patients despite best resuscitative measures.2 CPR, which is conventionally deemed to be life-saving for patients, appears as an aerosol-generating procedure risking lives of HCPs caring for flagyl giardia patients with buy antibiotics. Protected code blue algorithm has been formulated to address both performer and patient safety.3POCUS-INTEGRATED CPR.

WHY THE NEED IN flagyl giardia buy antibiotics?. Danilo Buonsenso and colleagues have described buy antibiotics era as demanding less stethoscope and more ultrasound usage in clinical practice.4 PPE is now an essential measure for HCP protection, and goggles used as a part of PPE are associated with fogging and poor visibility. This coupled with the inability to confirm endotracheal tube position with stethoscope due to poor accessibility in PPE, increases the risk of oesophageal intubation, re-intubation attempts, aerosol generation and thus HCP exposure. Bedside ultrasound could act flagyl giardia as visual stethoscope in the described scenario. Sono-CPR in buy antibiotics can help intervene quickly in treatable cases and reduce the time spent by HCP in futile resuscitative efforts.

Reduced time spent equates to reduced duration of aerosol exposure and thus reduced risk of transmission. Various algorithms are flagyl giardia described for sono-cardiopulmonary resuscitation (sono-CPR) during cardiac arrest, but none are discussed to address patients with buy antibiotics.5 It would hence be wise to integrate bedside point-of-care ultrasound (POCUS) in the code blue algorithm.HOW THE BEDSIDE TOOL HELPS?. Hypoxemia and respiratory failure attribute over 80% aetiology of cardiac arrest in patients with buy antibiotics.1 Prioritising oxygenation and ventilation using definitive airway and use of high-efficiency particulate air filters reduces airborne transmission, thereby making early intubation the dictum of resuscitation.3 Considering poor visualisation due to fogging with the goggles and face shield, inability to use stethoscope and lack of availability of end-tidal CO2 (EtCO2) in resource constraint settings, ultrasound-guided real-time intubation by trained HCP or endotracheal tube (ETT) placement confirmation post intubation could prove beneficial. Confirming ETT placement and direct visualisation of oesophagal lumen can be done using a linear ultrasound probe.6 In cases of oesophageal intubation, tissue-air hyperechoic lines are visualised in both trachea and oesophagus, referred to as ‘double-track sign’.State of hypercoagulability and myocardial dysfunction exist in patients with buy antibiotics, hence increasing flagyl giardia the likelihood of myocardial infarction or pulmonary thromboembolism as aetiologies of cardiac arrest.7 Regional wall motion abnormality, dilated right atrium or right ventricle, plethoric inferior vena cava are easily identified by goal-directed echocardiography. Pneumothorax has been reported in patients with buy antibiotics, and ultrasound can identify absence of lung sliding, helping in quick needle thoracocentesis in arrest and peri-arrest cases.

Few cases of cardiac tamponade owing to myopericarditis have also been reported and bedside ultrasound can help diagnose and perform pericardiocentesis in such patients.Literature suggests that the chances of Return Of Spontaneous Circulation (ROSC) and survival to hospital admission at 24 hours is better in patients with baseline cardiac activity rather than no baseline cardiac activity. In patients with no baseline cardiac activity on arrival, one can withhold CPR, thereby protecting the HCP in this resource-intensive, aerosol-generating futile resuscitative effort.8 Asystole could be the flagyl giardia disguised entity of fine ventricular fibrillation, which can be confirmed by fibrillatory cardiac activity on transthoracic echocardiography and can be defibrillated, thereby increasing the chances of earlier ROSC.9POCUS-INTEGRATED CPR. THE PROPOSED ALGORITHMCPR is a chaotic scenario, and to prevent added chaos, there is a need for a well-trained ultrasound performer placed in an appropriate area (figure 1). Intubating room needs to consist of minimal necessary number of HCPs, and all of them should be equipped with full PPE. Ultrasound device could be a potential fomite facilitating cross-transmission and flagyl giardia requires adequate protection of machine and its components with a transparent cover, sheet or bag.

When unavailable, low-level disinfectant solution should be used between each patient.Proposed algorithm for integration of POCUS during CPR in patients with buy antibiotics with team dynamics. The illustration is original work of the authors Dr flagyl giardia Brunda RL and colleagues. CPR, cardiopulmonary resuscitation. HCP, healthcare professional. POCUS, point-of-care flagyl giardia ultrasound.

PPE, personal protective equipment. RA, right atrium. RV, right flagyl giardia ventricle. VF, ventricular fibrillation. USG, ultrasonography." data-icon-position data-hide-link-title="0">Figure 1 Proposed algorithm for integration of POCUS during CPR in patients with buy antibiotics with team dynamics.

The illustration is original work of the authors Dr Brunda flagyl giardia RL and colleagues. CPR, cardiopulmonary resuscitation. HCP, healthcare professional flagyl giardia. POCUS, point-of-care ultrasound. PPE, personal protective equipment.

RA, right atrium flagyl giardia. RV, right ventricle. VF, ventricular fibrillation. USG, ultrasonography.When a patient experiences cardiac arrest, there is a need for HCPs with full PPE to check pulse and begin CPR flagyl giardia as per standard guidelines. After 2 min of CPR, if there is no ROSC, during the 10 second pause for rhythm assessment, a trained HCP can perform POCUS in a stepwise manner.

Each step needs to be performed individually during flagyl giardia 10 second pause without prolonging delay between chest compressions and compromising the quality of CPR. Any treatable aetiology identified during the algorithm requires immediate intervention.Step 1. Assess cardiac activity—Sub-xiphoid view can be procured and cardiac activity assessed. If absent, consider termination of efforts, and if present, resuscitative efforts can be continued.After repeating flagyl giardia 2 min cycle of CPR, if there has been no ROSC, consider hypoxic aetiology as the cause of arrest in patients with buy antibiotics and intubate without delay. Withholding chest compressions during intubation is recommended.3Step 2.

Assess ETT placement—At the level of thyroid gland, above the suprasternal notch, place ultrasound probe transversely and visualise the oesophagus.10 If the posterior wall of oesophagus is obscured by a dark acoustic shadow or if there is ‘double-track’ sign, consider failed endotracheal intubation and perform immediate re-intubation.Step 3. Assess lung for pneumothorax—Assess lung sliding, and if absent look for ‘stratosphere sign’ in M-mode flagyl giardia of ultrasound.10 If detected, perform immediate needle thoracocentesis.Step 4. Assess for Cardiac etiology of arrest—Obtain sub-xiphoid window preferably, and look for the presence of cardiac tamponade, chamber dilatation or collapse, regional wall motion abnormality and cardiac contractility.Availability of trained personnel and smaller portable ultrasound devices makes its use during cardiac arrest plausible.CPR with the help of POCUS could thus prove to improve chances of ROSC and also reduced transmission to HCP by early identification, treatment of reversible causes and avoidance of prolonged efforts. Sono-CPR appears to be more HCP-friendly than prolonged blind CPR and necessitates its utility in the era of buy antibiotics addressing performer safety as well as patient safety..

Former Editor-in-Chief of the Postgraduate Medical Journal Dr Barry Ian Hoffbrand died suddenly on April 24, 2020 at the age of 86.A prominent member of a generation of very bright young doctors at flagyl online in canada University College Hospital (UCH) in London who went on to distinguished careers, he was much admired for his http://www.ec-exen-pire-schiltigheim.ac-strasbourg.fr/?slideshow=larbre-de-vie keen intellect, clinical perception and skills, gentle good humour and kindly nature, combined with a wonderfully sharp intelligence. Professor Dame Jane Dacre remembered him as ‘a kind, witty, clever man, and a great physician’.He was born in Bradford, West Yorkshire, to Philip Hoffbrand, a bespoke tailor, and Minnie (née Freedman), both from Jewish families from Eastern Europe. After Bradford Grammar School, he went up to read medicine from 1952 to 1956 at The Queen’s College, Oxford, where he was a keen member of the college flagyl online in canada cricket team—the Quondams. He was pleased to feature in the 1950s on the silver Quondams Cup.

Clinical training on a Goldsmid scholarship followed from 1956 to 1958 at UCH Medical School, London, where he was awarded prizes in clinical pathology and haematology. His postgraduate medical flagyl online in canada training was mainly at UCH, where he was house physician to Max (later Lord) Rosenheim, after an initial 6 months at St Luke’s Hospital, Bradford. He also spent a year as senior research fellow from 1967 to 1968 at the Cardiovascular Research Institute, at the University of California Medical Center in San Francisco. Barry’s research on cardiovascular physiology lead to a DM in 1971 from Oxford University.Barry was appointed in 1970 as a consultant physician at the Whittington Hospital and honorary senior clinical lecturer at UCH Medical School, with interests in general and …INTRODUCTIONAs cardiac arrest occurs in around 20% of the patients with severe buy antibiotics, a large number of them will require immediate resuscitative efforts.1 Cardiopulmonary resuscitation (CPR) in buy antibiotics flagyl has become a source of speculation and debate worldwide.

Healthcare professionals (HCPs) resuscitating this subset of patients are subject to fears and enormous mental stress pertaining to risk of transmission, breach in personal flagyl online in canada protective equipment (PPE), unsure effectiveness of PPE and nevertheless bleak positive outcomes in patients despite best resuscitative measures.2 CPR, which is conventionally deemed to be life-saving for patients, appears as an aerosol-generating procedure risking lives of HCPs caring for patients with buy antibiotics. Protected code blue algorithm has been formulated to address both performer and patient safety.3POCUS-INTEGRATED CPR. WHY THE flagyl online in canada NEED IN buy antibiotics?. Danilo Buonsenso and colleagues have described buy antibiotics era as demanding less stethoscope and more ultrasound usage in clinical practice.4 PPE is now an essential measure for HCP protection, and goggles used as a part of PPE are associated with fogging and poor visibility.

This coupled with the inability to confirm endotracheal tube position with stethoscope due to poor accessibility in PPE, increases the risk of oesophageal intubation, re-intubation attempts, aerosol generation and thus HCP exposure. Bedside ultrasound flagyl online in canada could act as visual stethoscope in the described scenario. Sono-CPR in buy antibiotics can help intervene quickly in treatable cases and reduce the time spent by HCP in futile resuscitative efforts. Reduced time spent equates to reduced duration of aerosol exposure and thus reduced risk of transmission.

Various algorithms are described for sono-cardiopulmonary resuscitation (sono-CPR) during cardiac arrest, but none are discussed to address patients with buy antibiotics.5 It would hence be wise to integrate flagyl online in canada bedside point-of-care ultrasound (POCUS) in the code blue algorithm.HOW THE BEDSIDE TOOL HELPS?. Hypoxemia and respiratory failure attribute over 80% aetiology of cardiac arrest in patients with buy antibiotics.1 Prioritising oxygenation and ventilation using definitive airway and use of high-efficiency particulate air filters reduces airborne transmission, thereby making early intubation the dictum of resuscitation.3 Considering poor visualisation due to fogging with the goggles and face shield, inability to use stethoscope and lack of availability of end-tidal CO2 (EtCO2) in resource constraint settings, ultrasound-guided real-time intubation by trained HCP or endotracheal tube (ETT) placement confirmation post intubation could prove beneficial. Confirming ETT placement and direct visualisation of oesophagal lumen can be done using a linear ultrasound probe.6 In cases of oesophageal intubation, tissue-air hyperechoic lines are visualised in both trachea and oesophagus, referred to as ‘double-track sign’.State of hypercoagulability and myocardial dysfunction exist in patients with buy antibiotics, hence increasing the likelihood of myocardial infarction or pulmonary flagyl online in canada thromboembolism as aetiologies of cardiac arrest.7 Regional wall motion abnormality, dilated right atrium or right ventricle, plethoric inferior vena cava are easily identified by goal-directed echocardiography. Pneumothorax has been reported in patients with buy antibiotics, and ultrasound can identify absence of lung sliding, helping in quick needle thoracocentesis in arrest and peri-arrest cases.

Few cases of cardiac tamponade owing to myopericarditis have also been reported and bedside ultrasound can help diagnose and perform pericardiocentesis in such patients.Literature suggests that the chances of Return Of Spontaneous Circulation (ROSC) and survival to hospital admission at 24 hours is better in patients with baseline cardiac activity rather than no baseline cardiac activity. In patients with no baseline cardiac activity on arrival, one can withhold CPR, thereby protecting the HCP in this resource-intensive, aerosol-generating futile resuscitative effort.8 Asystole could be the disguised entity of fine ventricular fibrillation, which can be confirmed by fibrillatory cardiac activity on transthoracic echocardiography and can be defibrillated, thereby increasing flagyl online in canada the chances of earlier ROSC.9POCUS-INTEGRATED CPR. THE PROPOSED ALGORITHMCPR is a chaotic scenario, and to prevent added chaos, there is a need for a well-trained ultrasound performer placed in an appropriate area (figure 1). Intubating room needs to consist of minimal necessary number of HCPs, and all of them should be equipped with full PPE.

Ultrasound device could be a potential fomite facilitating cross-transmission and requires adequate protection flagyl online in canada of machine and its components with a transparent cover, sheet or bag. When unavailable, low-level disinfectant solution should be used between each patient.Proposed algorithm for integration of POCUS during CPR in patients with buy antibiotics with team dynamics. The illustration is flagyl online in canada original work of the authors Dr Brunda RL and colleagues. CPR, cardiopulmonary flagyl 200mg buy online resuscitation.

HCP, healthcare professional. POCUS, point-of-care ultrasound flagyl online in canada. PPE, personal protective equipment. RA, right atrium.

RV, right flagyl online in canada ventricle. VF, ventricular fibrillation. USG, ultrasonography." data-icon-position data-hide-link-title="0">Figure 1 Proposed algorithm for integration of POCUS during CPR in patients with buy antibiotics with team dynamics. The illustration is original work flagyl online in canada of the authors Dr Brunda RL and colleagues.

CPR, cardiopulmonary resuscitation. HCP, healthcare professional flagyl online in canada. POCUS, point-of-care ultrasound. PPE, personal protective equipment.

RA, right atrium flagyl online in canada. RV, right ventricle. VF, ventricular fibrillation. USG, ultrasonography.When a patient experiences cardiac arrest, there is a need for HCPs with flagyl online in canada full PPE to check pulse and begin CPR as per standard guidelines.

After 2 min of CPR, if there is no ROSC, during the 10 second pause for rhythm assessment, a trained HCP can perform POCUS in a stepwise manner. Each step needs to be performed individually during flagyl online in canada 10 second pause without prolonging delay between chest compressions and compromising the quality of CPR. Any treatable aetiology identified during the algorithm requires immediate intervention.Step 1. Assess cardiac activity—Sub-xiphoid view can be procured and cardiac activity assessed.

If absent, consider termination of efforts, and flagyl online in canada if present, resuscitative efforts can be continued.After repeating 2 min cycle of CPR, if there has been no ROSC, consider hypoxic aetiology as the cause of arrest in patients with buy antibiotics and intubate without delay. Withholding chest compressions during intubation is recommended.3Step 2. Assess ETT placement—At the level of thyroid gland, above the suprasternal notch, place ultrasound probe transversely and visualise the oesophagus.10 If the posterior wall of oesophagus is obscured by a dark acoustic shadow or if there is ‘double-track’ sign, consider failed endotracheal intubation and perform immediate re-intubation.Step 3. Assess lung for pneumothorax—Assess lung sliding, and if flagyl online in canada absent look for ‘stratosphere sign’ in M-mode of ultrasound.10 If detected, perform immediate needle thoracocentesis.Step 4.

Assess for Cardiac etiology of arrest—Obtain sub-xiphoid window preferably, and look for the presence of cardiac tamponade, chamber dilatation or collapse, regional wall motion abnormality and cardiac contractility.Availability of trained personnel and smaller portable ultrasound devices makes its use during cardiac arrest plausible.CPR with the help of POCUS could thus prove to improve chances of ROSC and also reduced transmission to HCP by early identification, treatment of reversible causes and avoidance of prolonged efforts. Sono-CPR appears to be more HCP-friendly than prolonged blind CPR and necessitates its utility in the era of buy antibiotics addressing performer safety as well as patient safety..

How should I take Flagyl?

Take Flagyl by mouth with a full glass of water. Take your medicine at regular intervals. Do not take your medicine more often than directed. Take all of your medicine as directed even if you think you are better. Do not skip doses or stop your medicine early.

Talk to your pediatrician regarding the use of Flagyl in children. Special care may be needed.

Overdosage: If you think you have taken too much of Flagyl contact a poison control center or emergency room at once.

NOTE: Flagyl is only for you. Do not share Flagyl with others.

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Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population.

The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb. Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over.

The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition. In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids.

The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the two conditions remains unclear,” she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition.

The other authors on this paper were Ginette A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit.

The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors. - Click to Tweet The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows.

The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells.

As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an . These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma.

The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow. Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types was unclear.

To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients with different tumor types. Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation.

The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer. €œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive.

It’s one of those things that doesn’t sound right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint inhibitors.

However, he explains, this cancer type is often caused by a flagyl, which seems to encourage a strong immune response despite the cancer’s lower mutational burden. In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs haven’t yet been tried.

Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs. €œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says.

Yarchoan receives funding from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb. Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries.

During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition. In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls.

Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the two conditions remains unclear,” she says. However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition.

The other authors on this paper were Ginette A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit. The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors.

- Click to Tweet The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows. The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells. As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an .

These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma. The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow. Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types was unclear.

To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients with different tumor types. Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation. The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer.

€œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive. It’s one of those things that doesn’t sound right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint inhibitors. However, he explains, this cancer type is often caused by a flagyl, which seems to encourage a strong immune response despite the cancer’s lower mutational burden.

In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs haven’t yet been tried. Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs. €œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says.

Yarchoan receives funding from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

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Www.digitalhealth.gov.auMedia release - Electronic prescriptions rolling out to support Melbourne.docx (168KB)Media release - Electronic prescriptions rolling out to support Melbourne.pdf (76KB).