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Journal club (JC) is an integral part of postgraduate medical education. Although several innovations have been attempted to improve its effectiveness, the influence of the number of sessions remains unexplored. The current study investigated the effect of the number of sessions (one vs. four) of conduction of journal club on critical appraisal skills of postgraduate students at two institutions. A quasi-experimental study was conducted comparing the effectiveness of JC in a one- versus four-session JC format using two objective tests: Critical Appraisal Skills Test (CAST) and Population, Intervention, Comparison, Outcome (PICO) score. The degree of changes (pre-JC vs. post-JC session) after each format exposure, association of prescores to postscores, and correlation between the CAST and PICO scores were discerned. CAST score was higher in the four-session format (P = 0.03), whereas PICO score increased in the single-session format of JC (P = 0.03). Also, the change in CAST score was higher in the four-session versus single-session JC format (P = 0.04). We conclude that a four-session format of JC is more effective in augmenting critical appraisal skills of postgraduate students, whereas a single session is sufficient for improving factual knowledge.

This research was carried out to develop a homemade, nutrient-rich milk cake for the Indian festive season. This milk cake has been prepared with condensed milk, aloe vera gel, and honey as a sweetener. Each component utilized has undergone a thorough analysis to determine its nutritional worth. Energy (72.96 kcal), total protein (1.12 g), total carbohydrate (17.24 g), total fat (0.11 g), total sugar (0.83 g), vitamin C (4.49), calcium (27 mg), potassium (46 mg), iron (2.15 mg), and salt (2.89 mg) All of these included in an analysis of aloe gel's nutritional content. While the total flavonoid concentration (3.90/100 g) and fibre content illustrate the antioxidant potential of aloe gel. The same kind of study was done on honey, taking into various factors like moisture percentage (17.2), reducing sugar (71.80), specific gravity at 27 °C (1.37), and total sugar (76.56) per 100 g. FTIR analysis of gel was also done during this work and it was observed throughout the duration of this assessment that the final product, which was made using just natural food ingredients and no chemicals, can prove to be a highly beneficial and popular appetite suppressant among individuals of all ages. This is owing to the fact it is energized and offers a variety of health advantages. [ABSTRACT FROM AUTHOR]

Background: Road traffic injuries are the seventh most common cause of long bone fractures. Following high velocity limb trauma, the defects in the long bone are usually associated with appreciable soft-tissue losses. These open long bone injuries always require multidisciplinary managements to reconstruct the composite defects of bone and soft tissue. Aims and Objectives: The aim of the study was to find out radiological and clinical outcome, complications, and union time in complex and non-union fractures of long bone managed by fibular graft. Materials and Methods: Out of 50 cases, 40 cases were of complex fractures and ten cases were of non-union. We used Fibular strut grafts in reconstruction of bone defects and soft tissue injury. Results: Thirty (60.0%) had excellent functional outcome, 10 (20.0%) had good, 6 (12.0%) had satisfactory, and 4 (8.0%) patients had poor outcome. Main complications were non-union 2 cases and 3 cases of superficial wound infection, which subsided by wound dressing and intravenous antibiotic treatment. Conclusion: Free fibular grafting has been proven to be an ideal choice in the management of large segmental bone defects as well as in situations of biological failure of bone healing. [ABSTRACT FROM AUTHOR]

Objective: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS).Methods: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review.Results: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine.Conclusions: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS. [ABSTRACT FROM AUTHOR]

ournal club (JC) is an integral part of postgraduate medical education. Although several innovations have been attempted to improve its effectiveness, the influence of the number of sessions remains unexplored. The current study investigated the effect of the number of sessions (one vs. four) of conduction of journal club on critical appraisal skills of postgraduate students at two institutions. A quasi-experimental study was conducted comparing the effectiveness of JC in a one- versus four-session JC format using two objective tests: Critical Appraisal Skills Test (CAST) and Population, Intervention, Comparison, Outcome (PICO) score. The degree of changes (pre-JC vs. post-JC session) after each format exposure, association of prescores to postscores, and correlation between the CAST and PICO scores were discerned. CAST score was higher in the four-session format (P 0.03), whereas PICO score increased in the singlesession format of JC (P 0.03). Also, the change in CAST score was higher in the four-session versus single-session JC format (P 0.04). We conclude that a four-session format of JC is more effective in augmenting critical appraisal skills of postgraduate students, whereas a single session is sufficient for improving factual knowledge. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is frequently associated with infertility, obesity, hypertension, and diabetes mellitus. Cardiac autonomic dysfunction is well documented in long-term patients of PCOS, with impairment being proportionate to disease duration. However, there is paucity of literature on cardiac autonomic tone in the "lean" phenotype of PCOS. We used exercise challenge to probe for autonomic dysfunction, as assessed by heart rate variability (HRV), an index of cardiac autonomic tone. Methods: Our study population consisted of 27 newly diagnosed PCOS patients and 25 healthy females matched by age and body mass index. Short-term HRV was assessed using time and frequency domain indices. Moderate, isotonic exercise was used as an interventional tool. Indices of both groups were compared in three bins – at baseline, immediate, and late postexercise stages. Results: The groups had comparable HRV indices at baseline. However, low-frequency (LF) power was significantly reduced in PCOS patients during immediate and late postexercise phases when compared with controls (p = 0.03 and 0.03, respectively). Time domain indices also exhibited a fall postexercise, although not statistically significant. Conclusions: Although "lean" phenotype PCOS patients had comparable HRV parameters as controls at baseline, the administration of exercise challenge led to reduced sympathetic drive, evident by reduced LF power in patient group. This may be due to latent autonomic dysfunction in "lean" PCOS, which is unmasked on exposure to exercise challenge. We propose that the evaluation of HRV response to exercise may serve as a sensitive screening tool to detect early cardiovascular dysfunction in newly diagnosed lean PCOS patients. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease accounts for more than 40% of mortality in rheumatoid arthritis (RA) with cardiovascular autonomic nervous system dysfunction (CAD) being commonly observed. Since few studies are available regarding the status of cardiac autonomic function in RA, we planned to study the same in RA patients and correlate it with their level of inflammatory markers and disease severity. Objectives: 1. To study the heart rate variability (HRV), inflammatory markers in RA and controls. 2. To assess the correlation of inflammatory markers and disease severity with HRV. Materials and Methods: The study was conducted on 35 diagnosed cases of RA and 35 controls. Short term heart rate variability was taken as an index of autonomic function. TNF-α and IL-10 were assessed in 3 ml overnight fasting serum. Severity of RA was assessed by DAS28 score. Result: Disease severity of RA was low. LF, NN50 and RANGE were significantly decreased in RA patients. TNF-α was significantly elevated in RA patients. Correlation of TNF-α with LF/HF ratio and DAS28 with RMSSD, NN50 and HF were found to be significantly positive. Conclusion: CAD is significantly correlated with inflammatory activity and disease severity in RA. HRV may serve as an accurate tool to screen RA patients for early signs of autonomic disturbance, which can greatly help to reduce future morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (http://www.cdisc.org/therapeutic#MS) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies. [ABSTRACT FROM AUTHOR]

Alterations in the autonomic cardiovascular control have been implicated to play an important etiologic role in preeclampsia. The present study was designed to evaluate autonomic functions in preeclamptic pregnant women and compare the values with normotensive pregnant and healthy nonpregnant controls. Assessment of autonomic functions was done by cardiovascular reflex tests and by analysis of heart rate variability (HRV). Cardiovascular reflex tests included deep breathing test (DBT) and lying to standing test (LST). HRV was analyzed in both time and frequency domain for quantifying the tone of autonomic nervous system to the heart. The time domain measures included standard deviation of normal R-R intervals (SDNN) and square root of mean squared differences of successive R-R intervals (RMSSD). In the frequency domain we measured total power (TP), high frequency (HF) power, low frequency (LF) power, and LF/HF ratio. Cardiovascular reflex tests showed a significant parasympathetic deficit in preeclamptic women. Among parameters of HRV, preeclamptic group had lower values of SDNN, RMSSD, TP, HF, and LF (ms2) and higher value of LF in normalised units along with high LF/HF ratio compared to normotensive pregnant and nonpregnant controls. Furthermore, normotensive pregnant women had lower values of SDNN, TP, and LF component in both absolute power and normalised units compared to nonpregnant females. The results confirm that normal pregnancy is associated with autonomic disturbances which get exaggerated in the state of preeclampsia. [ABSTRACT FROM AUTHOR]

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Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, “EDSS-Plus,” defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors’ times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression. [ABSTRACT FROM AUTHOR]

Introduction: The QTc interval is affected by heart rate, autonomic nervous system and diseases like diabetes. However, the affect of exercise which alters autonomic nervous system activity, on QTc is not clear. On the other hand, the incidence of sudden cardiac death increases many fold post exercise. These events may be better explained by studying the effect of exercise on QTc. Aim: This study was designed with an aim to record the QTc interval changes in response to isometric exercise in a group of normal individuals with or without parental history of diabetes mellitus. Also the QTc duration was correlated with the LF-HF ratio. Materials and Methods: Twenty nine, healthy medical students were subjected to isometric hand grip test for 5min. ECG was recorded pre-exercise and at various time intervals post-exercise. Statistical Analysis: All data are expressed in mean ± SD. Intra group comparison was done using paired t-test and unpaired t-test was used for comparison among group I and group II subjects, and among males and females. Result: The difference in the pre and post exercise QTc values both within and between groups was statistically significant with group I subjects recording lower values. The post exercise LF: HF values were significantly increased when compared to pre exercise values in both the groups. There was no correlation between LF: HF and QTc. Conclusion: A longer than normal QTc interval predisposes to arrhythmia. Exercise brings about detectable changes in the QTc interval after a period of isometric exercise in normal individuals which in high risk individuals may predispose to sudden cardiac death. In addition women may be more susceptible to post-exercise arrhythmia owing to a longer QTc even at rest. [ABSTRACT FROM AUTHOR]

Context: Premenstrual stress affects 75% of women of childbearing age and yoga has been found to be beneficial in many psycho-somatic disorders. Aims: To investigate the effect of integrated yoga on autonomic parameters and psychological well-being during both pre and post phases of menstrual cycle in healthy young female subjects. Settings and Design: Present study is a randomized control trial and was conducted in the Department of Physiology, Lady Hardinge Medical College, New Delhi, India. Material and Methods: Fifty apparently healthy females in the age group of 18-20 years were randomized into two groups: Group I (n=25) consisted of subjects who practiced yoga 35-40 minutes per day, six times per week for the duration of three menstrual cycles. Training was given by qualified yoga instructor. Group II (n=25) subjects acted as controls. Following parameters were recorded at the beginning and after completion of three menstrual cycles in all the subjects: Height, weight (BW), Resting Heart Rate (HR), Resting Systolic (SBP) and Diastolic Blood Pressure (DBP), parasympathetic reactivity tests including Expiration-Inspiration Ratio (E: I ratio) and 30:15 ratio, sympathetic reactivity tests including BP changes due to Isometric Hand Grip (IHG) exercise, and Cold Pressor Test (CPT). Assessment of psychological status was done by administering DIPAS (Defense Institute of Physiology and Allied Sciences) inventories of Anger self report scale, Trait Anxiety, Sense of well-being and Depression scale. Statistical Analysis: Intra-group comparison of physiological parameters was done by using paired 't' test, whereas intragroup comparison of non-parameteric data such as scores of anxiety, depression, anger and sense of well-being was done by Wilcoxon signed-rank test. Inter-group comparison of parameters was done by Students 't' test for parametric tests and Mann-Whitney 'U' test for non-parameteric tests. Results: There was significantly higher BW, resting SBP, DBP, sympathetic activity and blunting of parasympathetic reactivity and also, significantly higher scores of anger, depression, anxiety and decreased score of well-being in premenstrual phase as compared to postmenstrual phase in both the groups in initial cycle. There was significantly higher percentage decrease in BW, HR, SBP & DBP in yoga group as compared to control group in both the phases from initial to second and onwards between second and third menstrual cycle. Also, decrease in anger, depression and anxiety and increase in well-being score was significant in yoga group as compared to control group from initial to second and third cycle in premenstrual phase while the change was significant only in depression score in postmenstrual phase. Conclusion: Our study shows that there was significant alteration of autonomic functions and psychological status in premenstrual phase when compared with postmenstrual phase in young healthy females. Also, regular practice of yoga has beneficial effects on both phases of menstrual cycle by bringing parasympathodominance and psychological well-being probably by balancing neuro-endocrinal axis. [ABSTRACT FROM AUTHOR]

Objective: Lamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment. Methods: SPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12–24 and 0–24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored. Results: Treatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12–24 months p = 0.043, Nfh 0–24 months p = 0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin. Conclusions: The relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration. [ABSTRACT FROM AUTHOR]

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. [ABSTRACT FROM AUTHOR]

The article supports the use of advanced magnetic resonance imaging (MRI) measures like (DTI) and functional MRI as outcome measures in future clinical trials. Issues and concerns tackled are limitations of magnetization transfer ratio (MTR), optical coherence tomography (OCT) and positron emission tomography (PET) and the potential of MRI techniques as practical approach for developing biomarkers for drug pipelines.

Background and objective Adolescents in general make poor food choices due to a lack of awareness, social pressure, and other factors, leading to a faulty lifestyle. On the other hand, the adolescent athletic population is associated with a healthy eating pattern. In light of this, this study aimed to evaluate the eating behavior of adolescent cyclists competing at the national level. Methods A total of 50 national-level adolescent cyclists (26 males and 24 females) were assessed for eating behavior, daily food consumption patterns, and eating habits around exercise time by using a pre-tested validated questionnaire, Food Frequency Questionnaire (FFQ), and 24-hour Food Recall. Results The majority (82%) of the cyclists were non-vegetarians, followed by lacto-vegetarians (14%) and lacto-ovo vegetarians (14%). Of note, 72% of the cyclists consumed four meals consisting of breakfast, lunch, snacks, and dinner daily, while 28% skipped at least one of the meals. The preference for takeaways (52%) surpassed dine-outs (34%) and home-cooked (14%) food. Pre-training snack was consumed by 37% and post-training snack by 47%. Cyclists daily consumed breakfast cereals (76%), bread (94%), pulses (92%), fruits (100%), vegetables (62%), milk (84%), milk products (90%), egg (82%), poultry, fish, and meat (74%), dry fruits, nuts, and seeds (78%), and saturated fats (100%). Junk foods (94%) and sweetened beverages (70%) were consumed at least once a week. No significant difference was observed in eating behavior and daily food consumption pattern between male and female cyclists. Conclusion The eating behavior of adolescent cyclists was inclined towards the consumption of saturated fats, junk food, and sweetened beverages. Male and female athletes have similar food habits. There is a need for the implementation of behavior change-oriented nutrition strategies to inculcate healthy eating habits among adolescent cyclists., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Golla et al.)

Background Medical education is a rigorous formal education with a vast syllabus. Burnout and stresses are common among medical students and more prominent in females. Female medical students suffer from a higher level of stress than male medical students. For the improvement of physical and mental health, meditation, pranayama, and yoga are some of the ancient techniques. Meditation is a technique of focusing the mind on a target like an object, activity, or any thought. Pranayama is an ancient yogic practice focusing on the breath. Yoga is a combination of physical, mental, and spiritual dimensions that has the potential to improve mental and physical health. Objective This study aimed to find the effect of meditation, pranayama, and yoga on the improvement of mental health among female undergraduate medical students. Materials and methods This was an interventional study. A total of 105 females with a median age of 19 years (first quartile - third quartile: 18-20) first-year undergraduate medical students were recruited for this study. They were randomly allocated to control, meditation, pranayama, and yoga groups. The control group did not practice any form of meditation, pranayama, or yoga. The rest of the group practiced a designated program for their group, six days a week for 12 weeks. The anxiety, depression, anger, and sense of well-being were assessed by a validated self-administered questionnaire developed by the Defence Institute of Physiology and Allied Sciences, New Delhi before starting the study, at six weeks, and at 12 weeks after the intervention. Inter-group levels of anxiety, depression, anger, and well-being were compared by the Kruskal-Wallis test with Dunn's posthoc test. Intra-group parameters at baseline, at six weeks, and at 12 weeks after the intervention was tested by Friedman's test. Result The age (years) (p = 0.07), height (cm) (p = 0.98), and weight (kg) (p = 0.26) of participants among groups were similar. Anxiety, depression, and anger significantly decreased after six weeks in all three intervention groups. A further decrement was seen after 12 weeks of meditation, pranayama, and yoga. The maximum effect was seen in the yoga group. A sense of well-being was improved after practicing all types of interventions. However, meditation was found to increase a sense of well-being to the highest level compared to pranayama and yoga. Conclusion Introduction and sustainment of meditation, pranayama, and yoga programs for first-year female undergraduate medical students may help reduce anxiety, depression, and anger and promote a sense of well-being. Although a six-week program helps to improve mental health, a 12-week program helps in further improvement. A yoga program is more effective for improving the mental health of the students in comparison with pranayama and meditation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, . et al.)

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed., Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19., Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients., Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237)., Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality., Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09])., Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults., Trial Registration: ClinicalTrials.gov: NCT04332991.

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability., Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials., Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials., Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.

Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function., Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment., Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT., Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone., Conclusion: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.

Objectives:  Blood pressure estimation is a key skill for medical practitioners. It is routinely taught to undergraduate medical students using an aneroid sphygmomanometer. However, the conceptual understanding in the practical remains limited. We conducted the following study to evaluate the efficacy of digital data acquisition systems as an adjunct to the sphygmomanometer to teach blood pressure., Methods:  Fifty-seven first-year medical students participated in the study. An MCQ test of 15 questions, consisting of 10 conceptual and five factual questions, was administered twice - pre- and post-demonstration of blood pressure measurement using a digital data acquisition system. In addition, qualitative feedback was also obtained., Results:  Median scores were 7 (6 - 8) and 3 (1.5 - 4) in pre-test sessions for conceptual and factual questions, respectively. Post-test scores showed a significant improvement in both categories (10 (9 - 10) and 4 (4 - 4.5), respectively, Mann-Whitney U test, p < 0.0001). Student feedback also indicated that the digital system enhanced learning and student participation., Conclusions:  Student feedback regarding the demonstrations was uniformly positive, which was also reflected in significantly improved post-test scores. We conclude that parallel demonstration on digital systems and the sphygmomanometer will enhance student engagement and understanding of blood pressure measurement., Competing Interests: The authors have declared that no competing interests exist.

Measurement of blood pressure is an integral part of clinical examination. Over the years various types of instruments have been used to measure blood pressure but till date the mercury sphygmomanometer is regarded as the gold standard. However, there is a myth prevalent among health professionals regarding the level of the manometer in relation to heart at the time of measuring of blood pressure. Many professionals insist that it has to be placed at the level of the heart. We argue that the limb from which pressure is measured must be at the heart level rather than the manometer. We conducted a study in which we measured the blood pressure in adults by placing the manometer at three different levels with respect to the heart. The values of blood pressure obtained at all levels were similar and did not show any statistically significant difference. We therefore conclude that the level of sphygmomanometer per se does not affect blood pressure measurement.

Purpose: To present a new acquisition and analysis protocol for reliable and reproducible segmentation of the entire intraorbital optic nerve (ION) mean cross-sectional area by means of magnetic resonance imaging (MRI) at 3 tesla (T)., Methods: Eight healthy volunteers (mean age 31, five were male) gave written informed consent and both of their IONs were imaged individually using a coronal-oblique T2-weighted fast multidynamic image acquisition scheme; the proposed acquisition scheme has its rationale in combining separately acquired volumes and registering them to account for motion-related artifacts commonly associated with longer acquisitions. Mean cross-sectional area of each ION was measured using a semiautomated image analysis protocol that was based on an active surface model previously described and used for spinal cord imaging. Reproducibility was assessed for repeated scans (scan-rescan) and repeated image analysis performance (intraobserver)., Results: Mean and SD values of the left ION cross-sectional area for the eight healthy volunteers were 5.0 (±0.7) mm² and for the right ION were 5.3 (±0.8) mm². Mean scan-rescan coefficient of variation (COV) for the left ION was 4.3% and for the right was 4.4%. Mean intraobserver COV for the left ION was 2.1% and for the right was 1.8%., Conclusions: This study presents a new MRI acquisition and analysis protocol for reliable and reproducible in vivo measurement of the entire ION mean cross-sectional area as demonstrated in a pilot study of healthy subjects. The protocol presented here can be used in future studies of the ION in disease state.

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.