REPRESENTATION AND EXTRAPOLATION: EVIDENCE FROM CLINICAL TRIALS.

This article examines the consequences and causes of low enrollment of Black patients in clinical trials. We develop a simple model of similarity-based extrapolation that predicts that evidence is more relevant for decision-making by physicians and patients when it is more representative of the group being treated. This generates the key result that the perceived benefit of a medicine for a group depends not only on the average benefit from a trial but also on the share of patients from that group who were enrolled in the trial. In survey experiments, we find that physicians who care for Black patients are more willing to prescribe drugs tested in representative samples, an effect substantial enough to close observed gaps in the prescribing rates of new medicines. Black patients update more on drug efficacy when the sample that the drug is tested on is more representative, reducing Black-white patient gaps in beliefs about whether the drug will work as described. Despite these benefits of representative data, our framework and evidence suggest that those who have benefited more from past medical breakthroughs are less costly to enroll in the present, leading to persistence in who is represented in the evidence base.

Microbial dysbiosis and the aging process: a review on the potential age-deceleration role of Lactiplantibacillus plantarum.

Gut microbiota dysbiosis has been a serious risk factor for several gastric and systemic diseases. Recently, gut microbiota's role in aging was discussed. Available preclinical evidence suggests that the probiotic bacteria Lactiplantibacillus plantarums (LP) may influence the aging process via modulation of the gut microbiota. The present review summarized compelling evidence of LP's potential effect on aging hallmarks such as oxidative stress, inflammation, DNA methylation, and mitochondrial dysfunction. LP gavage modulates gut microbiota and improves overall endurance in aging animal models. LP cell constituents exert considerable antioxidant potential which may reduce ROS levels directly. In addition, restored gut microbiota facilitate a healthy intestinal milieu and accelerate multi-channel communication via signaling factors such as SCFA and GABA. Signaling factors further activate specific transcription factor Nrf2 in order to reduce oxidative damage. Nrf2 regulates cellular defense systems involving anti-inflammatory cytokines, MMPs, and protective enzymes against MAPKs. We concluded that LP supplementation may be an effective approach to managing aging and associated health risks.

A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

Spectrum of Febrile Thrombocytopenia in the Pediatric Population (1-18 Years) Admitted in a Tertiary Care Center.

Aim Thrombocytopenia is a common manifestation of various infections. Thrombocytopenia associated with fever helps to narrow down the differential diagnosis and management of fever. It also helps to know the various complications of thrombocytopenia, its management, and the outcome of the patient. This study aimed to evaluate the clinical profile and determine etiology and complications in patients with fever and thrombocytopenia in pediatric populations. Methods One hundred and fifteen patients of both sexes aged 1-18 years with fever and found to have thrombocytopenia (platelet count < 1.5 lakhs) between June 1, 2018 and March 31, 2019 were included in this study. Results Infection was the common cause of febrile thrombocytopenia and dengue fever was the most common infection. Bleeding manifestations were seen in 9.6 % of patients. Petechiae/purpura was the commonest bleeding manifestation followed by gum and nose bleeding. Common bleeding manifestations were seen in patients with a platelet count below 50,000 and the majority of them did not require platelet transfusion. Good recovery was noted in 96.5% of patients while 2.6% had mortality. Conclusions An infection, particularly dengue, was the common most cause of fever with thrombocytopenia. In the majority of patients, thrombocytopenia was transient and asymptomatic. Bleeding was present in the majority of patients with platelets less than 10,000 and 20,000 to 50,000. The most common bleeding manifestation was petechial rashes over the skin. Platelet transfusion was not required in most of the cases. On treating the specific cause, a drastic improvement in the platelet count was noted during discharge and further follow-up. Immunization is highly recommended for vaccine-preventable diseases.

Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

BACKGROUND: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. AIM: Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. RESULTS: Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. CONCLUSION: TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.

Clinico-Serological Profile of Infective Causes of Acute Hepatitis in Children Admitted to a Tertiary Care Centre.

BACKGROUND: Hepatitis is a major cause of healthcare burden in India. Hepatitis A is the most common cause of acute viral hepatitis in the pediatric population whereas hepatitis E virus (HEV) is the most important cause of epidemic hepatitis. Various other causes of acute infective hepatitis in children are dengue, malaria, and enteric fever. The aim of the present study is to understand the clinico-serological profile in cases of acute infective hepatitis in children.  Methodology: The present study is a cross-sectional study that was carried out from 1 September 2017 to 31 March 2019. A total of 89 children in the age group 1-18 years with clinically suspected acute infective hepatitis and subsequent confirmation on laboratory tests were included in the study. RESULTS: Hepatitis A (48.3%) was found to be the most common aetiology followed by dengue (22.5%) and hepatitis E (12.4%). No cases of hepatitis B or hepatitis C were found. The most common presenting complaint was fever (90%) and the most common clinical finding was icterus (69.7%). The sensitivity of icterus for the diagnosis of hepatitis was found to be 70%. Lab investigations showed a significant association between different etiologies of infective hepatitis with packed cell volume (PCV), white blood cell (WBC) count, and platelet count. Levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were raised in samples of patients with hepatitis A, hepatitis E, and combined hepatitis A and E infection as compared to other causes. All cases of hepatitis A and E were diagnosed with positive IgM antibody tests to the respective viral antigens. The most common complication was hepatic encephalopathy which was seen in patients with hepatitis A, dengue, and septicemia. Around 99% of patients recovered well and were discharged. One death occurred in a case of septicemia with septic shock with multiple organ dysfunction syndrome (MODS). CONCLUSION: The most common cause of infective hepatitis in children is hepatitis A. Other causes like dengue, malaria, and typhoid should also be kept in mind. The absence of icterus does not rule out hepatitis. Lab investigations including serology are important to confirm the diagnosis of various causes of hepatitis. Timely immunization against hepatitis is strongly recommended.

A Novel Lightweight Deep Learning-Based Histopathological Image Classification Model for IoMT.

The unavailability of appropriate mechanisms for timely detection of diseases and successive treatment causes the death of a large number of people around the globe. The timely diagnosis of grave diseases like different forms of cancer and other life-threatening diseases can save a valuable life or at least extend the life span of an afflicted individual. The advancement of the Internet of Medical Things (IoMT) enabled healthcare technologies can provide effective medical facilities to the population and contribute greatly towards the recuperation of patients. The usage of IoMT in the diagnosis and study of histopathological images can enable real-time identification of diseases and corresponding remedial actions can be taken to save an affected individual. This can be achieved by the use of imaging apparatus with the capacity of auto-analysis of captured images. However, most deep learning-based image classifying models are bulk in size and are inappropriate for use in IoT based imaging devices. The objective of this research work is to design a deep learning-based lightweight model suitable for histopathological image analysis with appreciable accuracy. This paper presents a novel lightweight deep learning-based model "ReducedFireNet", for auto-classification of histopathological images. The proposed method attained a mean accuracy of 96.88% and an F1 score of 0.968 on evaluating an actual histopathological image data set. The results are encouraging, considering the complexity of histopathological images. In addition to the high accuracy the lightweight design (size in few KBs) of the ReducedFireNet model, makes it suitable for IoMT imaging equipment. The simulation results show the proposed model has computational requirement of 0.201 GFLOPS and has a mere size of only 0.391 MB.

Incidental complex repetitive discharges on needle electromyography.

INTRODUCTION/AIMS: Complex repetitive discharges (CRDs) are spontaneous electromyography (EMG) waveforms often associated with chronic neurogenic or myopathic diseases, but incidentally identified CRDs have also been described. In this study we describe the distribution and possible significance of incidentally seen CRDs in otherwise normal electrodiagnostic studies. METHODS: A retrospective chart review was performed of all patients with CRDs incidentally documented on otherwise normal electrodiagnostic studies at Mayo Clinic from January 2013 through December 2020. Each patient's clinical symptoms, referral reason, electrodiagnostic report, and imaging studies were analyzed using descriptive statistics. RESULTS: Ninety-four patients (86 females; mean age, 62 years; range, 20 to 86 years) and 107 CRDs were studied. The most common neuromuscular reasons for electrodiagnostic referrals included radiculopathy, peripheral neuropathy, and myopathy. Mean symptom duration was 43 months (range, 1 to 312 months). Eighty-five patients had a CRD identified in one muscle (range, in all patients, one to five muscles). CRDs were identified most frequently in tensor fasciae latae (n = 21), biceps brachii (n = 16), and gluteus maximus (n = 9). Of the 58 patients in whom imaging was available, 46 (79%) had abnormalities that corresponded to the myotome in which the CRDs were visualized, most commonly L5 (n = 19) and C6 (n = 12). Of these 46 patients, 28 (61%) were referred for radicular or limb pain. DISCUSSION: CRDs can be incidentally noted on otherwise normal electrodiagnostic studies, most commonly in L5 and C6 myotomes. The mechanism of CRDs in the absence of electrodiagnostic features of axon loss or remodeling is unknown.

A Plausible Association Between the Use of Elderberry and Autoimmune Hepatitis.

Hepatic injury due to dietary and herbal supplements can often share similar clinical characteristics with autoimmune hepatitis (AIH). Sambucus species, commonly known as elderberry, have been used in traditional medicine for centuries to prevent and treat respiratory problems. Although there are no clear reports on the association of elderberry with AIH or drug-induced hepatitis, there have been concerns about negative health manifestations linked to elderberry and the overproduction of inflammatory cytokines. In this article, we discuss a case of a patient who developed autoimmune hepatitis while on long-term elderberry-containing supplements and a probable association between the two.

Quality Improvement Initiative to Improve Hand Hygiene Compliance in Indian Special Newborn Care Unit.

Pilot data on Hand hygiene (HH) compliance using a standard World Health Organisation checklist for 1-week suggested only 20% compliance. So, we planned a Quality Improvement study to improve HH compliance among health care providers in our Special Newborn Care Unit from 20% to 60% over 12 months. METHODS: We did this study in 3 phases: Baseline phase (2 months), Intervention phase (8 months), and Postintervention phase (2 months). A multidisciplinary Quality Improvement team composed of doctors, nursing staff, and ward attendants was constituted. The team analyzed potential barriers to HH by Fishbone analysis. Three trained observers randomly selected two target Special Newborn Care Unit patients daily and collected data on HH compliance unobtrusively during the three 8-h shifts over 24 h. In addition, we tested a range of interventions using multiple Plan Do Study Act cycles: Staff education; Displaying posters; Round the clock availability of soap and hand rub; Staff felicitation; Group performance feedback. We also collected data on healthcare-associated infections in all three phases. RESULTS: The total observations for HH during the baseline, intervention, and postintervention phase were 1488, 5808, and 1464, respectively. The HH compliance improved from 27.2% to 57.1% in the postintervention phase. There was no difference in the healthcare-associated infections among the three phases. CONCLUSIONS: The HH compliance rates improved significantly but not to the desired extent. So, we planned to increase our workforce, and improve our training program and infrastructure.

Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies.

BACKGROUND: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker. OBJECTIVE: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). METHODS: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared. RESULTS: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD. CONCLUSION: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Exploring essential tremor: Results from a large online survey.

INTRODUCTION: Essential tremor (ET) is one of the most common movement disorders; however, many patients are misdiagnosed and do not receive effective treatment. It is important to better understand the diagnosis, symptoms and treatment patterns to improve care for those with ET. METHODS: Persons in the International Essential Tremor Foundation database were invited to complete an online survey, focusing on symptoms, diagnosis, and treatment of ET. RESULTS: The survey was emailed to 19,206 persons, with 2864 (14.9%) respondents. Mean age was 65.4 years, median age of tremor onset was 36-40 years, 61% were women, and 64% had a known family history of tremor. Forty-five percent saw multiple physicians before a diagnosis of ET with 65% being diagnosed by a neurologist. Current care is provided by a neurologist in 42%, a family physician in 26% and 28% do not see a physician for ET. Tremor was most commonly reported in the hands/arms (95%). The most commonly affected daily activities included writing, eating, drinking and carrying. Beta-blockers were the most commonly used treatment (42%); however, 33% had no benefit and 35% discontinued due to side effects. Of note, 33% had never received treatment for their tremor. CONCLUSION: This survey highlights the need for more effective treatments with greater tolerability. Increased awareness among physicians and patients in the diagnosis and treatment of ET is also warranted, with nearly half the respondents seeing multiple physicians before receiving an ET diagnosis and nearly 30% not seeing a physician and/or not receiving treatment for ET.

Copulatory Dyskinesia: Pathognomonic Manifestation of Tardive Dyskinesia.

Background: Copulatory or pelvic thrusting dyskinesia is a subtype of tardive dyskinesia (TD) which is caused by exposure to dopamine blocking agents. Phenomenology shown: A man exhibiting rhythmic, stereotypical pelvic thrusting movements. Educational value: Recognition of copulatory dyskinesia as a distinctive iatrogenic disorder helps prevent unnecessary investigations and guides the implementation of corrective strategies.

Levodopa-Responsive Chorea: A Review.

BACKGROUND: Chorea is one of the disabling movement disorders, and the number of drugs which can treat this disorder effectively is limited. Tetrabenazine and deutetrabenazine are the two drugs approved by the US-FDA for the treatment of chorea associated with HD. Levodopa can improve chorea in some disorders, and this review aims to provide information on the use of levodopa in chorea. METHODS: A literature search was performed in February 2019 using the following terms "levodopa chorea," "levodopa TITF-1," levodopa brain-lung-thyroid syndrome," and "levodopa Huntington's Disease." The information regarding the etiology, outcome, and dose of levodopa was collected. RESULTS: We found a total of 18 cases in the literature where the benefit was reported with levodopa. Majority of the cases were brain-thyroid-lung (BTL) syndrome (50%). Another 5 cases were HD (Huntington's Disease), one with PCH type 2 (Pontocerebellar hypoplasia type 2), one with meningovascular syphilis, and two patients with Sydenham chorea. The patients with BTL syndrome responded to a very low dose of levodopa. DISCUSSION: This review suggests that levodopa has the potential to improve chorea in BTL syndrome while its use in chorea due to other disorders requires further study. BTL syndrome due to NKX2-1 mutation responded to levodopa while we did not find any case of chorea due to ADCY-5 mutation responding to levodopa.