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Glycogen storage disorders (GSDs) are inherited metabolic disorders characterized by defects in glycogen metabolism, leading to abnormal glycogen accumulation in various tissues. Pompe’s disease, a severe form of GSD, results from a deficiency in the enzyme acid alpha-glucosidase (GAA), causing lysosomal glycogen accumulation, primarily affecting cardiac and skeletal muscles. This case study presents a 45-day-old female infant with Pompe’s disease, initially presenting with fever, cough, cold, and respiratory distress. Clinical assessment revealed tachypnoea, elevated heart rate, hypotension, hepatosplenomegaly, elevated liver enzymes, and metabolic acidosis. Diagnostic tests confirmed Pompe’s disease through low alpha-glucosidase activity. Despite initiating antibiotic treatment and ventilatory support, the patient’s condition worsened, necessitating re-intubation. Pompe’s disease presents a broad spectrum of clinical manifestations, with early diagnosis and intervention being crucial for managing the infantile form. Enzyme replacement therapy (ERT) with recombinant human GAA has markedly improved patient outcomes, yet challenges remain, including variability in treatment response and the high cost of therapy. Ongoing research focuses on novel therapeutic approaches and enhancing patient care. This case underscores the importance of early recognition and comprehensive management to improve prognosis in Pompe’s disease.

This case report delves into the complexities surrounding Edwards syndrome (Trisomy 18), a chromosomal abnormality stemming from meiotic disjunction. Initially reported in 1960, Edwards syndrome is the second most prevalent autosomal trisomy following Down syndrome, affecting between 1 in 3500 and 1 in 7000 individuals, with a slight male predominance. The majority of cases involve parents under 30 years old. A review of 152 cases demonstrates a myriad of anomalies, including severe intellectual deficits, congenital heart problems and distinct facial features. This report aims to enhance understanding of Edwards syndrome by presenting a comprehensive case study detailing the diagnosis and distinctive clinical features of a newborn with Trisomy 18. This case report helps in understanding the complexity of genetics and clinical manifestations, highlighting the importance of prenatal diagnosis and counseling, multidisciplinary care approaches, parental decision-making, palliative care and the need for further research. The case report underscores the necessity for heightened public awareness and support for affected families. This study contributes to the body of knowledge regarding Trisomy 18, fostering a more compassionate and informed approach to managing this challenging genetic disorder, ultimately aiming to improve the quality of life for those affected by Edwards syndrome.

Summary: Background: Coronary angioplasty and stent insertion is a first line treatment for patients with coronary artery disease, however it is complicated in the long-term by in-stent restenosis (ISR) in a proportion of patients with an associated morbidity. Despite this, currently there are no effective treatments available for the prevention of ISR. Repeat percutaneous revascularisation carries increased risks of major adverse cardiovascular events and a higher incidence of stent failure. In this study we report the efficacy of dietary inorganic nitrate in the prevention of ISR in a prospective, double-blind, randomised controlled trial. Methods: NITRATE-OCT is a double-blind, randomised, single-centre, placebo-controlled phase II trial. 300 patients who were planned to undergo percutaneous coronary intervention (PCI) and drug eluting stent (DES) implantation for stable angina were randomised on a 1:1 basis to receive a daily dose of either dietary inorganic nitrate or placebo for 6 months. Block randomisation was used and patients stratified according to diabetes status. The patients then underwent quantitative coronary angiography (QCA) at baseline and at 6 months and optical coherence tomography at 6 months to quantify ISR. The primary endpoint was the QCA quantified decrease of in-stent/in-segment diameter from the baseline measure at 6 months i.e., in-stent and in-segment late-lumen loss (LLL). The study is registered with ClinicalTrials.gov, number NCT02529189. Findings: From November 1st 2015 and March 31st 2020, NITRATE-OCT enrolled 300 patients with angina, with 150 each randomised to receive 70 mL of nitrate-containing beetroot juice or placebo (nitrate-deplete) juice for 6 months. Procedural characteristics were similar between the groups. The primary endpoint was available in 208 patients: 107 and 101 in the nitrate and placebo groups, respectively. There was a statistically significant effect of inorganic nitrate on both primary endpoints: in-stent LLL decreased by 0.16 mm (95% CI:0.06–0.25; P = 0.001) with mean = 0.09 ± 0.38 mm in the inorganic nitrate group versus 0.24 ± 0.33 mm in the placebo group; (P = 0.0052); and in-segment LLL decreased by 0.24 mm (95% CI:0.12–0.36; P

Ichthyosis, derived from the Greek word "ichthys" meaning fish, encompasses various skin disorders characterized by dry, scaly, and thickened skin, often inherited through autosomal or X-linked modes. This case report discusses a rare and severe form known as Harlequin ichthyosis, presenting a second gravida woman with consanguinity history who delivered a male baby with characteristic features including porcelain-like skin, ectropion, eclabion, and flexion deformities. Despite supportive measures, the baby died shortly after birth. Harlequin ichthyosis, with an incidence of 1 in 300,000 births, arises from mutations in the ABCA12 gene, affecting lipid exocytosis and desquamation. Antenatal diagnosis is feasible through ultrasound findings and genetic testing, with a grim prognosis and limited survival beyond infancy. This report underscores the challenges in managing such conditions and highlights the importance of ongoing research for better understanding and management.

Introduction: Janani Shishu Suraksha Karyakram (JSSK) is a key program for increasing the institutional delivery. This program is a boon for pregnant women who still deliver at home as well as for sick neonates who die on account of poor access to health facilities. Thus, current cross sectional analytical study was conducted to assess any Out-of-pocket expenditure (OOPE) by beneficiaries of JSSK. Methodology: 400 rural & urban beneficiaries of JSSK were enrolled from western part of India. Informed consent was sought & data about demographic profile, JSSK utilization & OOPE was collected in pre tested semi structured proforma. Results: Mean age of the beneficiaries was 24.87 years. 29.25% had to pay money availing the services. Most of the OOPE was for drugs & consumables. Age, age at marriage, religion, place of delivery, family size, having RSBY card, type of delivery, parity were predictors of OOPE among JSSK beneficiaries. Conclusions: Approximately 70% of beneficiaries received support through JSSK, yet around 30% still incurred expenses for healthcare services, highlighting the financial challenges faced.

Abstract Background Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine. Methods DiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination. Discussion This study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine. Trial registration ClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central – Oxford C Research Ethics Committee (21/SC/0154).

Abstract Background Post-COVID-19 syndrome is a result of triggering various immune pathways and metabolic disturbances. Basti is an important per rectal Ayurveda-based treatment having multi-targeted actions. Basti and Rasayana treatment modulate immune responses by regulating pro-inflammatory cytokines, immune globulins, and functional properties of T cell. We propose to study the clinical evaluation of Basti along with Rasayana (rejuvenation therapy) on symptoms of post-COVID 19 syndrome. Methods and analysis We designed a prospective, open-labeled proof of concept pragmatic study. The study duration is 18 months, and the intervention period are 35 days from the day of enrollment of the patients. The patients will be treated on the basis of Ayurvedic classification of Santarpanottha (over nutrition) symptoms and Apatarpanottha (lack of nutrition) symptoms. The Santarpanottha group will be treated within 3–5 days of oral Guggulu Tiktak Kashayam followed by 8 days of Yog Basti treatment and then 21 days of Rasayana therapy with Brahma Rasayan. The Apatarpanottha group will be treated within 3–5 days of oral Laghumalini Vasant, followed by 8 days of Yog Basti treatment and then 21 days of Kalyanak Ghrit. The outcome measures of this study will be to evaluate the changes in fatigue severity scale, MMRC dyspnea chest pain scale, pain score assessed by VAS scale, smell and taste scale, WOMAC scale, Hamilton depression scale, Hamilton anxiety scale, Insomnia Severity Index, change in Cough Severity Index, facial aging scale, dizziness scale, Pittsburgh Sleep Severity Quality Index, functional status scale, and heart palpitation scale. All adverse events will be monitored at each time throughout the study visit time. A total of 24 participants will be recruited to demonstrate with 95% confidence interval and 80% power. Discussion Ayurveda treats Santarpanottha (originated from over nutrition) symptoms and Apatarpanottha (symptoms originated from undernutrition) symptoms differently; hence, inspite of the same disease or symptom management, changes depend upon the type of the origin. This pragmatic clinical study is developed on the fundamental grounds of Ayurveda. Ethics and dissemination Ethics approval was obtained through the Institutional Ethics Committees of Government Ayurved College and Hospital on 23 July 2021. Trial registration The trial is prospectively registered with the Clinical Trial Registry of India on 17 August 2021 [CTRI/2021/08/035732] after the Institutional Ethics Committee approval [GACN/PGS/Synopsis/800/2021 Date 23/7/2021].

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2−) reductase activity leading to nitric oxide (·NO). Since these products express important, and often diametrically opposite, biological activity, consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurring hXDH mutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide ·NO formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·- and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance of XDH mutations. We also show that, in presence of inorganic NO2−, XOR-driven O2·- production is substantially reduced. We suggest that targeting enzyme activity to enhance the NO2−-reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease.

Abstract Background Since MTHFR is the key enzyme in folate metabolism, its reduction can lead to hyperhomocysteinemia, which can have a negative impact on pregnancy outcome. Moreover, MTHFR polymorphism has also been linked with oxidative stress and genotoxicity. Identifying its ethnicity-specific association can help to reduce the incidence of preterm birth (PTB). Material and methods: Age-matched preterm birth mothers ( 37 weeks) were carefully selected for the study. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was adopted to analyse MTHFR C677T polymorphism. Oxidative stress (OS) analysis was performed by measuring the levels of antioxidants (superoxide dismutase (SOD) and catalase (CAT)) and OS damage markers (lipid peroxidation (LPO), total protein). Genotoxicity was confirmed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The statistical analysis was performed by Student’s t test, chi-square test, and one-way ANOVA. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results The MTHFR polymorphism showed statistical significance for PTB outcome with CT and TT genotype frequencies at p

Gastrointestinal neuroendocrine tumours are hypothesised to arise from cells in the gastrointestinal tract's diffuse neuroendocrine system. The occurrence of Gastrointestinal Stromal Tumours (GIST) along with other primary gastrointestinal malignancies is not common. More than 60% of the GIST occurs in stomach and 37% in jejunum. GIST can coexist with single well-differentiated, occasional neuroendocrine tumours of small size. In terms of preventing metastatic illness, an adequate first curative approach combined with meticulous follow-up appears to have a substantial effect. Although a synchronous incidence of gastrointestinal tumours without any associated disorders is uncommon, any gastrointestinal tumour should be thoroughly investigated to rule it out. We report the case of coexistence of a high risk of neuroendocrine tumour along with gastrointestinal tumour in a 30-year-old male patient. Postoperative chemotherapy with imatinib 40 mg once a day for 6 months was given and followed-up. Patient had no recurrence for 6 months.

The COVID-19 pandemic forced health systems to rapidly shift to deliver healthcare virtually, however, there is a limited understanding of this shift from the patient's perspective. We conducted semi-structured interviews with patients in three clinical areas (mental health, chronic care, and surgical care) and used patient journey mapping to visualize their experiences. Themes suggest that (1) patient's preference of modalities was contextually dependent, (2) that providers must continually converse with patients to select appropriate modalities, and (3) that providers must account for multiple factors such as a patient's digital and health literacy, comfort level with the modality and their medical needs.

Pruritus is a common dermatological condition observed in patients with diabetes, making it a dermatometabolic condition. Being multiaethiological, pruritis is caused by autoimmune, genetic, infectious and various systemic diseases. The present survey aimed to understand the knowledge, attitude and practice toward pruritus among Indian physicians and patients with diabetes presenting with pruritus. A telephonic, cross-sectional, qualitative survey was conducted among physicians and patients across five cities in India from July–August 2020. An open-ended discussion guide was used for the interview; the data were analyzed to check for common themes and trends. A majority of the consulting physicians (CPs) believed that uncontrolled diabetes is the main causal factor for pruritus in patients with diabetes and reported that currently there are no standard tests or treatment guidelines for its management. CPs emphasized proper monitoring and counseling to overcome current challenges. Patients reported a negative impact of pruritus on their daily activities and quality of life. The survey concluded that poor management of diabetes is one of the main causal factors for patients with diabetes presenting with pruritus in India. CPs emphasized controlling diabetes along with symptomatic treatment. For patients, pruritus has multifaceted effects on their health, overall well-being, and quality of life.

Background: Infantile colic is characterized by prolonged periods of inconsolable, incessant crying and persistent fussing in an otherwise healthy infant. It is a self-limiting condition, but causes significant stress to mothers. AIM: To observe the role of Lactobacillus reuteriDSM 17938 in reducing crying time in colicky infants in routine clinical practice. Methods: This was a prospective observational multicentric clinic-based study. Each practitioner included approximately 30 infants < 5 months of age with infantile colic who were prescribed L. reuteri DSM 17938 for a period of 21 days. There were four physical consultations and two telephonic consultations. The parents were given a daily diary to record the duration of crying and fussing episodes and a questionnaire was administered during the consultations. Results: A total of 120 infants with a mean age of 56.9 ± 34.2 days were included in this 28-day study. The mean crying time as reported by the parents in the subject diary reduced from 248.2 ± 101.2 min, 95% CI: 229.45, 266.94 at baseline to 45.6 ± 79.1 min 95% CI: 31.02, 60.31 at study end (P < 0.01). The clinical response (defined as reduction of 50% in crying time) was observed in 85% of subjects at study end. The fussiness and parental perception of colic recorded during the consultations were reduced by 66% and 72%, respectively, at study end. The maternal depression scores were reduced to 63% at study end. Conclusion: L. reuteri DSM 17938 was associated with a significant reduction in crying time in colicky infants, and showed improvement in maternal depression.

Introduction: It is estimated that India accounts for 25% of global tuberculosis (TB) burden of the world. Extra pulmonary tuberculosis (EPTB) constitute about 15-20% of all cases of TB. Aim: To study the use of Xpert MTB / RIF test to determine the prevalence of extra pulmonary tuberculosis. Material and Methods: The Xpert MTB/RIF assay was performed on all the non-respiratory samples as per protocol. The patient related data along with results was retrieved from record registers. Results: Among the total of 1333 samples, 135 samples were found to be MTB positive and nine as MDR EPTB. The numbers of patients were maximum in age group 15-60 years with male predominance. Among all the sample types, pleural fluid (n=628) contributed the most followed by CSF (n=300), ascetic fluid (n=206), pus (n= 106), FNAC of lymph node (n=56) and other body fluid (n=37). The percentage MTB positivity for lymph node was (20/56) highest as 35% followed by pus (35/106) 33%, other body fluid (n=4/37) 11%. Conclusion: The result of our study suggests that the Xpert MTB/RIF assay shows good potential for the diagnosis of EPTB including MDR status especially in our country where the TB is endemic.

Abstract Background Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. Method The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. Discussion The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. Trial registration ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Abstract Background The evidence for the effectiveness of e-mental health interventions among ethnic minorities is still preliminary. This mixed methods study investigates the feasibility of a culturally adapted, guided online intervention with the intention to understand how it works and for whom to inform refinement. It also examines its likely effectiveness in reducing suicidal ideation when compared with the treatment as usual. Methods Turkish migrants with mild to moderate suicidal thoughts were recruited from the general population using social media and newspaper advertisements. The intervention group obtained direct access to a 6-week guided online intervention while participants in the waiting list condition had to wait for 6 weeks. The intervention is based on an existing online intervention and was culturally adapted. Participants in both conditions completed baseline, post-test, and follow-up questionnaires on suicidal ideation (primary outcome), depression, worrying, hopelessness, suicide attempt and self-harm, acculturation, quality of life, and usability. In addition, participants were interviewed to examine the feasibility and mechanisms of action in more depth. The responses were analysed by inductive thematic analysis. Results Eighty-five people signed up via the study website, and we included 18 (10 intervention, 8 waitlist control). While the therapeutic benefits were emphasised (e.g. feeling connected with the intervention), the feasibility was judged to be low. The main reasons given were not having severe suicidal thoughts and not being represented by the culturally adapted intervention. No suicide attempts were recorded during the study. The suicidal ideation, depression, and hopelessness scores were improved in both groups. Conclusion Although intended to be a definitive trial, the current study became a feasibility study with process evaluation to understand the components and how they operate. The online intervention was not superior to the control condition. Future studies need to attend the implementation issues raised including measures of stigma, acculturation, and careful cultural adaptations alongside more attention to coaching and relational support. They should also consider how to improve engagement alongside selection of those who are motivated to use online interventions and offer alternatives for those who are not. Trial registration Netherlands Trial Register, NTR5028 . Registered on 1 March 2015

Summary: Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation.

Abstract Eosinophilic ulcer (EU) is a rare self‐limiting chronic benign lesion of the oral mucosa. It is an uncommon and benign disease, which may leading to diagnostic difficulties. Biopsy is recommended to rule out any malignant etiology.

Abstract Background People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. Methods/design The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. Discussion The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. Trial registration ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Background: Tigecycline is used as a last line of defence against Multidrug Resistant (MDR) strains, and increasing rates of resistance are a growing concern globally. Tigecycline resistance has been reported in various pathogens including Acinetobacter spp., Klebsiella spp., Enterobacter spp., E. faecalis, S. aureus, S. pneumoniae and Serratia marcescens. Aim and Objectives: To study Tigecycline susceptibility pattern of isolates of Enterobacteriaceae and Acinetobacter spp. from Respiratory Tract Infections (RTI) in a tertiary care hospital. Material and Methods: A total of 7573 respiratory samples were received in Microbiology Department of Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER) from 1st January 2018 to 31st December 2018. The samples were processed as per standard techniques. Identification and antimicrobial susceptibility testing was done by VITEK-2 Compact automated system and Kirby – Bauer Disc Diffusion Method as per CLSI Guidelines. Results: Out of total 7573 respiratory samples received in laboratory, 1017 (13.42%) were culture positive for pathogens. Klebsiella pneumoniae 420(41.29%) was predominantly isolated microorganism followed by Pseudomonas aeruginosa 206(20.25%) and Acinetobacter spp. 193(18.97%). Most of Gram negative organisms were resistant to commonly used antibiotics. Carbapenem resistance was observed as 67.25%. Conclusion: Overall Tigecycline resistance among Carbapenem Resistant Enterobacteriaceae (CRE) and Carbapenem Resistant Acinetobacter (CRA) was found to be 15.50% and 10.69% respectively. Although Tigecycline is a promising antibiotic for the treatment of infections caused by drug resistant problematic pathogens, Tigecycline resistance is most frequently observed in A. baumannii and Enterobacteriaceae, especially in MDR strains. Hence, we advocate judicious use of Tigecycline in MDR infections and it should be kept as reserve.

Abstract We report a case of lobular capillary hemangioma of the conjunctiva in a 32‐year‐old man, who had no history of eye surgery or trauma, and did not respond to topical corticosteroid therapy. He was treated successfully by surgical excision. Excisional biopsy confirms the diagnosis and rules out any malignant lesion in medically uncontrolled cases.

Objective: To summarize evidence from longitudinal observational studies to determine whether diabetes (types 1 and 2) is associated with the course of symptoms in people with frozen shoulder. Data Sources: A systematic literature search of 11 bibliographic databases (published through June 2021), reference screening, and emailing professional contacts. Study Selection: Studies were selected if they had a longitudinal observational design that included people diagnosed with frozen shoulder at baseline and compared outcomes at follow-up (>2wk) among those with and without diabetes at baseline. Data Extraction: Data extraction was completed by 1 reviewer using a predefined extraction sheet and was checked by another reviewer. Two reviewers independently judged risk of bias using the Quality in Prognostic Factor Studies tool. Data Synthesis: A narrative synthesis, including inspection of forest plots and use of the prognostic factor Grading of Recommendations, Assessment, Development and Evaluations framework. Twenty-eight studies satisfied the inclusion criteria. Seven studies were judged to be at a moderate risk of bias and 21 at a high risk of bias. Diabetes was associated with worse multidimensional clinical scores (moderate certainty in evidence), worse pain (low certainty in evidence), and worse range of motion (very low certainty in evidence). Conclusions: This review provides preliminary evidence to suggest that people with diabetes may experience worse outcomes from frozen shoulder than those without diabetes. If high-quality studies can confirm the findings of this review, then clinicians should monitor patients with frozen shoulder with diabetes more closely and offer further treatment if pain or lack of function persists long-term.

Background: Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with an increased risk of mental health (MH) disorders including antenatal and postnatal depression (PND), anxiety and post-traumatic-stress-disorder (PTSD). We hypothesized GDM and MH disorders will disproportionately affect individuals from Black, Asian and Minority Ethnic backgrounds. Methods: A systematic methodology was developed, and a protocol was published in PROSPERO (CRD42020210863) and a systematic review of publications between 1st January 1990 and 30th January 2021 was conducted. Multiple electronic databases were explored using keywords and MeSH terms. The finalised dataset was analysed using statistical methods such as random-effect models, subgroup analysis and sensitivity analysis. These were used to determine odds ratio (OR) and 95% confidence intervals (CI) to establish prevalence using variables of PND, anxiety, PTSD and stress to name a few. Findings: Sixty studies were finalised from the 20,040 data pool. Forty-six studies were included systematically with 14 used to meta-analyze GDM and MH outcomes. A second meta-analysis was conducted using 7 studies to determine GDM risk among Black, Asian and Minority Ethnic women with pre-existing MH disorders. The results indicate an increased risk with pooled adjusted OR for both reflected at 1.23, 95% CI of 1.00–1.50 and 1.29, 95% CI of 1.11–1.50 respectively. Interpretation: The available studies suggest a MH sequalae with GDM as well as a sequalae of GDM with MH among Black, Asian and Minority Ethnic populations. Our findings warrant further future exploration to better manage these patients. Funding: Not applicable

Abstract Background People with severe mental illness (SMI) are two to three times more likely to be overweight and obese than the general population and this is associated with significant morbidity and premature mortality. Although lifestyle interventions can support people with SMI to lose weight, some are unable to make the necessary lifestyle changes or, despite making the changes, continue to gain weight. Objective To assess the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, a once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis. Methods Design: a single-centre, double-blind, randomised, placebo-controlled trial. Setting: mental health facilities within Southern Health NHS Trust. Participants: 60 adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication will be recruited. Participants will be overweight or obese, defined by their baseline BMI which will be: • BMI ≥ 30 kg/m2 or • BMI ≥ 27 kg/m2 to

Background: Burns trauma represents a major cause of morbidity and mortality. Tackling the pain and providing a better healing with conventional therapies have been compared to that by using topical heparin application in < 40% burns. Aim and Objectives: To compare pain score, healing, duration of hospital stay after applying topical heparin and conventional treatment for burns < 40%. Material and Methods: A total of 80 patients were included in the study and divided into 2 groups Heparin (H) and Control (C) group with 40 patients in each group. H group received unfractioned Heparin 25,000 IU / 5ml and C group received silver based antimicrobial cream and paraffin gauze. Results: Maximum number of patients belonged to the age group (15-35years = 65.5%). The maximum number of patients who sustained thermal injuries was from 11-20% (23 patients) and 31-40% (22 patients). The patients in H group had a significant decrease in their pain score (p

Abstract Background Obesity is twice as common in people with schizophrenia as the general population and associated with significantly worsened psychiatric and physical health. Despite National Institute for Health and Care Excellence guidelines for the management of psychosis recommending that mental health services offer lifestyle programmes to people with schizophrenia to improve physical health, this is not currently occurring. The aim of the STEPWISE research programme was to develop a lifestyle intervention addressing obesity and preventing weight gain in people with schizophrenia, schizoaffective disorder, or first episode psychosis taking antipsychotic medication, through an approach and fundamental principles drawn from existing diabetes and diabetes prevention interventions. This paper describes the often under-reported process of developing such an intervention from first principles. Methods Following an extensive literature review, an iterative cycle of development with input from people with schizophrenia, mental healthcare professionals, facilitators, and other stakeholders, a new weight management intervention for the target group was developed. A set of four core weekly sessions was piloted in Sheffield, followed at 3-monthly intervals by three booster sessions and telephone support contact once every 2 weeks, to form an intervention lasting 12 months. Facilitators were provided with a 4-day training package to support delivery of the intervention. Results This paper reports the process of development, including challenges and how these were addressed. It describes how user input influenced the structure, topics, and approach of the intervention. The outcome of this process was a feasible and acceptable lifestyle intervention to support people with schizophrenia, schizoaffective disorder, or first episode psychosis to manage their weight. This pilot provided opportunities for refinement of the intervention and facilitator training prior to testing in a multi-centre randomised controlled trial. Key findings from the pilot were linked to accessibility, focus, uptake, and retention, which influenced session length, travel arrangements, refreshment, breaks, and supporting tools to incentivise participants. Conclusions The STEPWISE intervention has been evaluated in a randomised controlled trial in 10 mental health trusts in England, and the results will be published in the British Journal of Psychiatry and the NIHR Journals Library. Trial registration ISRCTN19447796. Date registered: 20/03/2014

Background: The global impact of COVID-19 pandemic continues to affect the lives of billions of people with recurrent waves. Healthcare systems are struggling to manage pre-existing patient care and recurring covid-19 demands. As a result, we evaluated the mental health impact using systematic review and meta-analysis.Methods: A comprehensive search was undertaken from April 2020 to 22nd January 2021 using multiple electronic databases. A systematic review protocol was developed and published on PROSPERO registration; CRD42020181481. A random-effects model was used to compute pooled estimates of anxiety, depression, PTSD, insomnia and suicidal thoughts.Findings: Our search yielded 11,295 studies and of those 287 met the inclusion criteria. The meta-analysis of 206 studies revealed minimal differences in prevalence of anxiety, depression, and PTSD among HCPs compared with the public during the pandemic but higher prevalence of suicidal thoughts/ideation or self-harm (11% vs 5.8%) and lower prevalence of wellbeing (28.2% vs 52.6%) among the public compared to HCPs.Interpretation: The pandemic has led to a high mental health burden especially amongst HCPs and higher suicidal ideation and lower wellbeing in general public which warrants further investigation and management globally. These findings highlight an emerging critical public health issue that requires urgent solutions.

Intradural disc herniation is a rare presentation of a common pathology, comprising around 0.28- 0.3% of all disc herniations. It occurs when disc material related to an intervertebral disc penetrates the spinal dura and lies in an intradural extramedullary location. A 60 years old male patient presented with complaints of low back pain and right lower limb radiculopathy of 2 weeks duration. Neurological examination revealed the weakness of extensor hallucis longus and ankle dorsiflexion with diminished sensation corresponding to fourth and fifth lumbar (L4-L5) dermatome on the right side. Magnetic resonance imaging showed a large sequestered fragment with intradural extensions and posterior longitudinal ligament tear. Intradural nerve root showed significant displacement with severe central canal and right lateral recess stenosis. Discectomy was performed along with the removal of the intradural extension. The postoperative course was uneventful.

Abstract Background Osteoarthritis (OA) is a leading cause of persistent pain and disability. Traditionally viewed as a slowly progressive disease, the impact of symptom variability on prognosis remains unclear. ‘Acute-on-chronic’ episodes are a well-recognised feature of many long-term conditions but only recently formally described in OA. This study aimed to develop a web-based data collection platform and establish key methodological design parameters, to develop a larger community-based study investigating acute flares of knee OA in England. Methods The study is a 9-week feasibility and pilot web-based observational case-crossover study. Adults aged ≥ 40 years registered with two general practices who had consulted their general practitioner for knee pain/OA in the last 2 years were recruited. Participants completed a baseline questionnaire and scheduled (control-period) questionnaires at follow-up weeks 1, 5, and 9. Participants were invited to self-declare via the website on any occasion they experienced a knee pain flare-up lasting ≥ 24 h. Upon notification, an event-driven (case-period) questionnaire comparable to the scheduled questionnaires was completed and daily measurements on the course and consequences were taken until resolution. A sub-study of 10 participants logged daily pain measurements. The analysis estimated key parameters including recruitment (selective non-participation, eligibility, consent), retention, and flare-up capture processes. Questionnaire completeness and website usability were evaluated. Results Of 442 patients invited, 14 completed baseline questionnaires. Eligibility rate was 26.9% (95% CI 19.3, 36.2), consent rate 53.6% (35.8, 70.5), and overall recruitment rate 3.2% (1.9, 5.2). Compared to those mailed, baseline responders were more likely to be male and ≥ 65 years, as were those reporting ≥ 1 flare-up. Eleven scheduled questionnaires were completed (mean response 35%). Although seven participants (50%) self-declared 11 flare-ups, only one event-driven questionnaire was completed and three participants contributed daily flare measurement for four flares. Missing data was ≤ 3.7% across completed baseline, scheduled, and event-driven questionnaires. Aspects of website usability require minor refinement. Conclusions Recruitment was not feasible with the current strategy. An evaluation of processes has suggested several substantial changes in design that may enhance recruitment, retention, and data quality in a future full-scale study.

Background: Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries to determine Mycobacterium tuberculosis relatedness. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken. Methods: We studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data for the relevant patients were extracted from the Enhanced Tuberculosis Surveillance system run by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, to samples from individuals with shared epidemiological risk factors, and to those with both characteristics. Findings: 1999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only co-residence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4. Interpretation: In the setting studied, this molecular epidemiological study shows MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage. Funding: Public Health England, Health Innovation Challenge Fund, NIHR Health Protection Research Unit Oxford, NIHR Oxford Biomedical Research Centre. Keywords: Mycobacterium tuberculosis, Research in context

Background. Alcohol consumption patterns in South Africa (SA) tend to be characterised by risky patterns of drinking. Taken together with the large burden of disease associated with HIV and tuberculosis (TB), heavy alcohol consumption patterns with these chronic conditions has the potential to compromise the efficacy of treatment efforts among such patients. Objective. To explore the characteristics, correlates and diagnoses of alcohol use disorders among chronic care patients in SA. Method. A cross-sectional survey was conducted in three public health clinic facilities in the North West Province of SA. A total of 1 322 patients were recruited from non-emergency waiting areas. Results. Proportions of patients with abstinence, hazardous, harmful and dependent consumption were determined using logistic regression. Of the patients screened, nearly half (45%) drank alcohol and, of these, 10% were classified as hazardous drinkers, 1.7% as harmful drinkers, and 1.6% as dependent drinkers (overall 3% alcohol use disorder). Abstinence proportions were 60% and 38% among women and men, respectively. Alcohol Use Disorders Identification Test scores for men were 63% higher than for women. The lowest patient abstinence proportion (47%) and highest dependent drinking (10%) was for TB. The highest abstinence proportion was for diabetes (65%), and the highest hazardous and harmful drinking was among TB (14%) and HIV (7%) patients. Conclusions. The high levels of risky drinking among chronic care patients, particularly among patients receiving treatment for HIV and TB, are concerning. Instituting appropriate screening measures and referral to treatment would be an important first step in mitigating the effects of risky alcohol use among chronic care patients.

The longitudinal changes in the tibiofibular relationship as the ankle valgus deformity progresses in patients with hereditary multiple exostoses (HME) are not well-known. We investigated the longitudinal changes and associating factors in the tibiofibular relationship during the growing period. A total of 33 patients (63 legs) with HME underwent two or more standing full-length anteroposterior radiographs. Based on the change in ankle alignments, thirty-five patients with an increase in tibiotalar angle were grouped into group V, and 28 patients with a decreased angle into group N. In terms of the change in radiographic parameters, significant differences were noted in the tibial length, the fibular/tibial ratio, and the proximal and distal epiphyseal gap. However, age, sex, initial ankle alignment, location of osteochondroma, and presence of tibiofibular synostosis did not affect the tibiofibular alignment. The tibial growth was relatively greater than the fibular growth and was accompanied by significant relative fibular shortening in the proximal and distal portions. In pediatric patients with HME, age, sex, initial ankle alignment, location of the osteochondroma, and synostosis did not predict the progression of the ankle valgus deformity. However, when valgus angulation progressed, relative fibular shortening was observed as the tibia grew significantly in comparison to the fibula.

This article discusses the provision of mental health services in low- and middle-income countries (LMICs) with a view to understanding the cultural dynamics–how the challenges they pose can be addressed and the opportunities harnessed in specific cultural contexts. The article highlights the need for prioritisation of mental health services by incorporating local population and cultural needs. This can be achieved only through political will and strengthened legislation, improved resource allocation and strategic organisation, integrated packages of care underpinned by professional communication and training, and involvement of patients, informal carers, and the wider community in a therapeutic capacity.

Background: Hamstring length assessment has an important value in Physiotherapy assessment and better outcome of patients. Purpose of the study was 1) To compare Active SLR and Active knee extension test values as per Kendall’s muscle-range assessment, 2) To compare Passive SLR and Passive knee extension test values as per Kendall’s muscle range assessment. Methods: Total 100 healthy individuals (age 20.83±1.17, 14 males, 86 females) participated in study. Goniometric assessment of hip flexion-extension and knee flexion was assessed followed by active and passive straight leg raising (ASLR and PSLR) and knee extension tests (AKE and PKE). Kendall’s formula was used to find hamstring muscle-range. ASLR and AKE results were compared for means and correlation was assessed. PSLR and PKE results were compared for means and correlation was assessed. Result: The average hamstring-range is about 79.34% (ASLR), 83.67% (PSLR), 77.92% (AKE), and 81.43% (PKE) of total joint range of hamstrings. There is significant difference between ASLR and AKE values and between PSLR and PKE values. Conclusion: Total hamstring excursion in all methods confirms Kendall’s statement. However difference between SLR and knee extension tests suggest that SLR values of hamstrings length and knee extension values of hamstrings length cannot be used interchangeably. Other mechanical factors may play role for the difference between these values. Implications: Sequence of Hip flexion and Knee extension for hamstring length assessment has a significant effect on results and it should be considered by therapist before clinical decision making.

Background: Pune was at the epicenter of Influenza A (H1N1) epidemic that struck the country during the middle of 2009. Initially all the persons with a positive PCR test for H1N1 were customarily admitted to the infectious disease hospital; but later on the facility for admission of severe category of patients was made available at two other hospitals in Pune city. Objectives: To know the epidemiological features of Influenza A (H1N1) during the initial stages of the epidemic. Method and Materials: All the patients admitted to the infectious disease hospital during June-October 2009 with a confirmed Influenza A (H1N1) PCR test were considered for the study. Statistical analysis: Mean, SD, Inter-quartile Range, Chi-square. Results: Less than 30 years comprised 87.6 percent and students were in majority (63.38%) out of the total 284 patients studied. The mean duration of illness for H1N1 was 6.8 days (inter-quartile range of 5-8 days). The clinical picture was almost similar in both male and female patients. Co-morbid conditions were observed in 15.8 percent patients. The complication rate in patients with respiratory co-morbid conditions was significantly higher. Initially, the proportion of patients with history of foreign travel was high; later on their proportion decreased to a very low level while an increase in the proportion of patients with history of contact with a known H1N1 patient was observed as the epidemic progressed. Nearly half of the families had not taken Oseltamivir chemoprophylaxis while 35.6 percent patients were administered Oseltamivir within 48 hrs of starting of symptoms. There was no mortality in the patients studied. Conclusions: A study of 284 confirmed cases of Influenza A (H1N1) in Pune city showed epidemiological features of the disease such as age, gender, history of contact, foreign travel, co-morbidity and complication rate and the Oseltamivir prophylaxis.

Teratoma is the most commonly encountered germ cell tumour among the most common ovarian tumours; however, teratomas of the omentum and mesentery are extremely rare. They are usually asymptomatic or can produce compressive symptoms. The imaging features are suggestive. The present report describes such a case of primary omental teratoma encountered in a young patient, which was managed by surgical resection. The histopathological examination confirmed the diagnosis of mature cystic teratoma. Germ cell tumors are congenital tumors containing derivatives of all the three germinal layers, frequently seen in gonads. But their occurrence in extragonadal sites, such as omental teratoma, is relatively rare.

Upper gastrointestinal (GI) bleeding is defined as bleeding proximal to the ligament of Treitz. The most important aspect of management of GI bleeding is to locate the site and cause of bleeding. The aim of the study is to find out the common etiology, presentation and management, including the role of upper GI endoscopy. Recent advances have meant that endoscopic hemostatic methods are now associated with a reduced rate of re-bleeding, cost, blood transfusion, length of hospital stay and mortality. A prospective study of 50 cases was carried out between August 2001 and July 2003. Patients with signs and symptoms suggestive of upper GI bleeding (UGIB) such as hematemesis, melena, aspirated blood from nasogastric tubes, profuse hematochezia, etc., were included in the study. The patients were selected randomly. The most common cause of UGIB in the present study was acute erosive gastritis (34%) followed by portal hypertension (24%) and peptic ulcer (22%). All 50 patients underwent upper GI endoscopy, of whom 39 patients were treated conservatively and 11 patients underwent endotherapy to control bleeding. Out of 39 patients treated non-endoscopically, 6 cases required laparotomy to control UGIB. 8 of 50 cases had past history of UGIB, 5 of whom had a previous history of endotherapy. One case was treated with devascularization as routine hemostatic methods failed. So, initial method of choice to control the bleeding was endotherapy and surgery was undertaken if an endoscopic method failed. The most common cause of hematemesis in our setting was acute erosive gastritis followed by portal hypertension. Endoscopy is a valuable minimal invasive method to diagnose and treat upper GI bleeding.