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Objectives We conducted a meta-synthesis of qualitative studies to synthesize the views of psychiatric patients on second-generation antipsychotics (SGAs) and the healthcare providers about the metabolic monitoring of adult-prescribed SGAs. Methods A systematic search was conducted in four databases through SCOPUS, PubMed, EMBASE, and CINAHL to identify qualitative studies of patients’ and healthcare professionals’ perspectives on the metabolic monitoring of SGAs. Initially, titles and abstracts were screened to exclude articles that were not relevant followed by full-text reading. Study quality was assessed by using Critical Appraisal Skills Program (CASP) criteria. Themes were synthesized and presented as per the Interpretive data synthesis process (Evans D, 2002). Results A total of 15 studies met the inclusion criteria and were analyzed in meta-synthesis. Four themes were identified: 1. Barriers to metabolic monitoring; 2. Patient related concerns to metabolic monitoring; 3. Support system by mental health services to promote metabolic monitoring; and 4. Integrating physical health with mental health services. From the participants’ perspectives, barriers to metabolic monitoring were accessibility of services, lack of education and awareness, time/resource constraints, financial hardship, lack of interest on metabolic monitoring, patient capacity and motivation to maintain physical health and role confusion and impact on communication. Education and training on monitoring practices as well as integrated mental health services for metabolic monitoring to promote quality and safe use of SGAs are the most likely approaches to promote adherence to best practices and minimize treatment-related metabolic syndrome in this highly vulnerable cohort. Conclusion This meta-synthesis highlights key barriers from the perspectives of patients and healthcare professionals regarding the metabolic monitoring of SGAs. These barriers and suggested remedial strategies are important to pilot in the clinical setting and to assess the impact of the implementation of such strategies as a component of pharmacovigilance to promote the quality use of SGAs as well as to prevent and/or manage SGAs-induced metabolic syndrome in severe and complex mental health disorders.

Objectives To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. Methods We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. Results We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel’s C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. Conclusions Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

Objectives To analyse various corneal nerve parameters using confocal microscopy along with systemic and orthoptic parameters in patients presenting with ocular surface pain using a random forest artificial intelligence (AI) model. Design Observational, cross-sectional. Methods Two hundred forty eyes of 120 patients with primary symptom of ocular surface pain or discomfort and control group of 60 eyes of 31 patients with no symptoms of ocular pain were analysed. A detailed ocular examination included visual acuity, refraction, slit-lamp and fundus. All eyes underwent laser scanning confocal microscopy (Heidelberg Engineering, Germany) and their nerve parameters were evaluated. The presence or absence of orthoptic issues and connective tissue disorders were included in the AI. The eyes were grouped as those (Group 1) with symptom grade higher than signs, (Group 2) with similar grades of symptoms and signs, (Group3) without symptoms but with signs, (Group 4) without symptoms and signs. The area under curve (AUC), accuracy, recall, precision and F1-score were evaluated. Results Over all, the AI achieved an AUC of 0.736, accuracy of 86%, F1-score of 85.9%, precision of 85.6% and recall of 86.3%. The accuracy was the highest for Group 2 and least for Group 3 eyes. The top 6 parameters used for classification by the AI were microneuromas, immature and mature dendritic cells, presence of orthoptic issues and nerve fractal dimension parameter. Conclusions This study demonstrated that various corneal nerve parameters, presence or absence of systemic and orthoptic issues coupled with AI can be a useful technique to understand and correlate the various clinical and imaging parameters of ocular surface pain.

The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.

Background Molecular tests in solid tumours for targeted therapies call for the need to ensure precision testing. To accomplish this participation in the External Quality Assessment Program (EQAS) is required. This evaluates the consistency of diagnostic testing procedures and offers guidance for improving quality. Outbreak of COVID-19 pandemic led to worldwide lockdown and disruption of healthcare services including participation in EQAS.The present study describes the extended scope of EQAS offered byMPQAP (Molecular Pathology Quality Assurance Program), the first proficiency test provider for solid tumor diagnostics in India. The study surveys the preparedness of molecular testing laboratories in routine diagnostics and participation for quality assessment scheme. Methods A documented guideline for measures and precautions to be carried by testing laboratories in performing routine diagnostic tests during the lockdown period were charted and distributed to all MPQAP participant centres. A survey was conducted for MPQAP participants to check whether laboratories were involved in COVID-19 testing and to evaluate the impact of lockdown on the operations of diagnostics procedures. From the acquired response of the survey, 2 cycles out of initially proposed 11 cycles were executed with transformed approach using digital tools and image interpretation modules. Findings Out of 25 solid tumour testing laboratories registered as participants, 15 consented to participate in survey. The summary of survey conveyed the impact of COVID-19onroutine operations of diagnostics tests such as shortcomings in inventory and human resource management. Thirteen participants showed active willingness and consented to participate in EQAS test scheme. Interpretations The survey findings and assessment of EQAS cycles endorsed the quality testing procedures carried by participating laboratories throughout the lockdown. It highlighted the utility of EQAS participation during pandemic along with emphasis on safety measures for continual improvement in quality of diagnostic services.

Glycogen storage disorders occur due to enzyme deficiencies in the glycogenolysis and gluconeogenesis pathway, encoded by 26 genes. GSD’s present with overlapping phenotypes with variable severity. In this series, 57 individuals were molecularly confirmed for 7 GSD subtypes and their demographic data, clinical profiles and genotype-phenotype co-relations are studied. Genomic DNA from venous blood samples was isolated from clinically affected individuals. Targeted gene panel sequencing covering 23 genes and Sanger sequencing were employed. Various bioinformatic tools were used to predict pathogenicity for new variations. Close parental consanguinity was seen in 76%. Forty-nine pathogenic variations were detected of which 27 were novel. Variations were spread across GSDIa, Ib, III, VI, IXa, b and c. The largest subgroup was GSDIII in 28 individuals with 24 variations (12 novel) in AGL. The 1620+1G>C intronic variation was observed in 5 with GSDVI (PYGL). A total of eleven GSDIX are described with the first Indian report of type IXb. This is the largest study of GSDs from India. High levels of consanguinity in the local population and employment of targeted sequencing panels accounted for the range of GSDs reported here.

Background Kidney transplant recipients are a unique cohort in regard to SARS-CoV 2 susceptibility and clinical course, owing to their immunosuppressed state and propensity for kidney injury. The primary purpose of this study is to ascertain if, in kidney transplant recipients, SARS-CoV 2 infection impacts long term renal allograft function. Methods This retrospective, single-center study reviewed 53 kidney transplant recipients with a positive SARS-CoV-2 PCR at NMH from January 1, 2020 to June 30, 2020. Results Change in eGFR from baseline kidney function prior to infection to 90 days after the first positive SARS-CoV 2 test was +1.76%, -17.5% and -23.16% the mild, moderate and severe disease groups respectively. There was a significant decline in kidney function in the moderate and severe disease cohorts as compared to the mild disease cohort, with respective p values of p = 0.0002 and p = 0.021. Relative to the mild disease cohort, the moderate and severe disease cohorts also demonstrated significantly increased risk of developing AKI (66%, 85%), both with p values of P = 0.0001. Conclusions Clinically severe SARS-CoV 2 infection is associated with greater risk of acute kidney injury and greater decline in renal allograft function at 90 days post infection, compared to mild disease.

Dental caries and periodontal disease are very common chronic diseases closely linked to inadequate removal of dental plaque. Powered toothbrushes are viewed as more effective at removing plaque; however, the conflicting evidence and considerable unexplained heterogeneity in their clinical outcomes does not corroborate the relative merits of powered tooth brushing. To explain the heterogeneity of brushing patterns with powered toothbrushes, we conducted a observational study of tooth brushing practices of 12 participants in their naturalistic setting. Integrated brush sensors and a digital data collection platform allowed unobtrusive and accurate capture of habitual brushing patterns. Annotated brushing data from 10 sessions per participant was chosen for scrutiny of brushing patterns. Analysis of brushing patterns from the total 120 sessions revealed substantial between- and within-participant variability in brushing patterns and efficiency. Most participants (91.67%) brushed for less than the generally prescribed two minutes; individual participants were also inconsistent in brushing duration across sessions. The time devoted to brushing different dental regions was also quite unequal. Participants generally brushed their buccal tooth surfaces more than twice as long as the occlusal (2.18 times longer (95% CI 1.42, 3.35; p < 0.001)) and lingual surfaces (2.22 times longer (95% CI 1.62, 3.10; p < 0.001); the lingual surfaces of the maxillary molars were often neglected (p < 0.001). Participants also varied in the epochs of excessive brushing pressure and the regions to which they were applied. In general, the occlusal surfaces were more likely to be brushed with excessive pressure (95% CI 0.10, 0.98; p = 0.015). Our study reveals that users of powered toothbrushes vary substantially in their use of the toothbrushes and diverge from recommended brushing practices. The inconsistent brushing patterns, between and within individuals, can affect effective plaque removal. Our findings underscore the limited uptake of generic oral self-care recommendations and emphasize the need for personalized brushing recommendations that derive from the objective sensor data provided by powered toothbrushes.

Made available in DSpace on 2021-06-25T10:46:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 BACKGROUND: There is ample evidence that gestational diabetes mellitus has a direct influence on urinary incontinence and pelvic floor muscles. There are no standardized pelvic floor muscle exercise programs in the literature for the physiotherapy and differ in the type of exercise, intensity, type and duration of application, and the frequency and duration of treatment sessions. The aim of this systematic review will be to investigate that Pelvic Floor Muscle Training can prevent and/or decrease the pregnancy specific urinary incontinence in women with gestational diabetes mellitus or gestational hyperglycemia. METHODS: We will perform a systematic review according to the Cochrane methodology of Randomized Controlled Trials. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases, with the date of consultation until June 2020. The MeSH terms used will be Pregnancy, Hyperglycemia, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1, Pregnancy in Diabetics, Diabetes, Gestational, Urinary Incontinence, Pelvic Floor Muscle Strength. Primary outcomes: improvement or cure of pregnancy specific urinary incontinence (which can be assessed by questionnaires, and tools such as tampon test, voiding diary, urodynamic study). Secondary outcomes: improvement of pelvic floor muscle strength (pelvic floor functional assessment, perineometer, electromyography, functional ultrasonography), improved quality of life (questionnaires), presence or absence of postpartum Urinary Incontinence and adverse effects. Quality assessment by Cochrane instrument. Metanalysis if plausible, will be performed by the software Review Manager 5.3. DISCUSSION: The present study will be the first to analyze the effectiveness of pelvic floor exercises in pregnant women with Gestational Diabetes Mellitus or Hyperglycemia, who suffer from pregnancy specific urinary incontinence. Randomized Controlled Trials design will be chosen because they present the highest level of evidence. It is expected to obtain robust and conclusive evidence to support clinical practice, in addition to promoting studies on the theme and contributing to new studies. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42017065281. Department of Physiotherapy and Occupational Therapy School of Philosophy and Sciences São Paulo State University (UNESP) Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP) Stricto Sensu Graduate Program in Nursing at UNIVERITAS Guarulhos University (UNG) Discipline of Evidence-Based Medicine Paulista School of Medicine-Federal University of São Paulo (EPM-UNIFESP) Department of Physiotherapy Universidade do Oeste Paulista (UNOESTE) Pelvic Care Center Maastricht Maastricht University Medical Center Department of Nursing Botucatu Medical School (FMB) São Paulo State University (UNESP) Department of Physiotherapy and Occupational Therapy School of Philosophy and Sciences São Paulo State University (UNESP) Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP) Department of Nursing Botucatu Medical School (FMB) São Paulo State University (UNESP)

ObjectiveTo evaluate the effects of changes in risk factors between the first two pregnancies on the occurrence of placental abruption (PA) in the same woman.MethodsRoutinely collected obstetric data from Aberdeen Maternity and Neonatal Databank, the Maltese National Obstetric Information System and the Finnish Medical Birth Register were aggregated. Records of the first two singleton pregnancies from women who had PA in one pregnancy but not the other, were identified from this pooled dataset. A case-crossover study design was used; cases were pregnancies with abruption and matched controls were pregnancies without abruption in the same woman. Conditional logistic regression was used to investigate changes in risk factors for placental abruption in pregnancies with and without abruption.ResultsA total of 2,991 women were included in the study. Of these 1,506 (50.4%) had PA in their first pregnancy and 1,485 (49.6%) in a second pregnancy. Pregnancies complicated by preeclampsia {194 (6.5%) versus 115 (3.8%) adj OR 1.69; (95% CI 1.23-2.33)}, antepartum haemorrhage of unknown origin {556 (18.6%) versus 69 (2.3%) adjOR 27.05; 95% CI 16.61-44.03)} and placenta praevia {80 (2.7%) versus 21 (0.7%) (adjOR 3.05; 95% CI 1.74-5.36)} were associated with PA. Compared to 20 to 25 years, maternal age of 35-39 years {365 (12.2) versus 323 (10.8) (adjOR 1.32; 95% CI 1.01-1.73) and single marital status (adjOR 1.36; 95% CI 1.04-1.76) were independently associated with PA. Maternal smoking, BMI and fetal gender were not associated with PA.ConclusionAdvanced maternal age, pregnancies complicated with unexplained bleeding in pregnancy, placenta praevia and preeclampsia were independently associated with a higher risk of placental abruption.

ObjectivePost-partum hemorrhage (PPH) is the leading direct cause of maternal mortality in India. Uterine balloon tamponade (UBT) is recommended for atonic PPH cases not responding to uterotonics. This study assessed cost-effectiveness of three UBT devices used in Indian public health settings.MethodsA decision tree model was built to assess cost-effectiveness of Bakri-UBT and low-cost ESM-UBT alternatives as compared to the recommended standard of care i.e. condom-UBT intervention. A hypothetical annual cohort of women eligible for UBT intervention after experiencing atonic PPH in Indian public health facilities were evaluated for associated costs and outcomes over life-time horizon using a disaggregated societal perspective. Costs by undertaking primary costing and clinical parameters from published literature were used. Incremental cost per Disability Adjusted Life Years (DALY) averted, number of surgeries and maternal deaths with the interventions were estimated. An India specific willingness to pay threshold of INR 24,211 (USD 375) was used to evaluate cost-effectiveness. Detailed sensitivity analysis and expected value of information analysis was undertaken.ResultsESM-UBT at base-case Incremental Cost-Effectiveness Ratio (ICER) of INR -2,412 (USD 37) per DALY averted is a cost-saving intervention i.e. is less expensive and more effective as compared to condom-UBT. Probabilistic sensitivity analysis however shows an error probability of 0.36, indicating a degree of uncertainty around model results. Bakri-UBT at an ICER value of INR -126,219 (USD -1,957) per DALY averted incurs higher incremental societal costs and is less effective as compared to condom-UBT. Hence, Bakri-UBT is not cost-effective.ConclusionFor atonic PPH management in India, condom-UBT offers better value as compared to Bakri-UBT. Given the limited clinical effectiveness evidence and uncertainty in sensitivity analysis, cost-saving result for ESM-UBT must be considered with caution. Future research may focus on generating high quality comparative clinical evidence for UBT devices to facilitate policy decision making.

Calcineurin inhibitors (CNI), the cornerstone of immunosuppression after transplantation are implicated in nephrotoxicity and allograft dysfunction. We hypothesized that combined low doses of CNI and Everolimus (EVR) may result in better graft outcomes and greater tolerogenic milieu. Forty adult renal transplant recipients were prospectively randomized to (steroid free) low dose Tacrolimus (TAC) and EVR or standard dose TAC and Mycophenolate (MMF) after Alemtuzumab induction. Baseline characteristics were statistically similar. EVR levels were maintained at 3-8 ng/ml. TAC levels were 4.5±1.9 and 6.4±1.5 ng/ml in the TAC+EVR and TAC+MMF group respectively. Follow up was 14±4 and 17±5 months respectively and included protocol kidney biopsies at 3 and 12 months post-transplantation. Rejection-rate was lower in the TAC+EVR group. However patient and overall graft survival, eGFR and incidence of adverse events were similar. TAC+EVR induced expansion of CD4+CD25hiFoxp3+ regulatory T cells as early as 3 months and expansion of IFN-γ+CD4+CD25hiFoxp3+ regulatory T cells at 12 months post-transplant. Gene expression profile showed a trend toward decreased inflammation, angiogenesis and connective tissue growth in the TAC+EVR Group. Thus, greater tolerogenic mechanisms were found to be operating in patients with low dose TAC+EVR and this might be responsible for the lower rejection-rate than in patients on standard dose TAC+MMF. However, further studies with longer follow up and evaluating impact on T regulatory cells are warranted.

In sequential competitions, the order in which teams take turns may have an impact on performance and the outcome. Previous studies with penalty shootouts have shown mixed evidence of a possible advantage for the first shooting team. This has led to some debate on whether a change in the rules of the game is needed. This work contributes to the debate by collecting an extensive dataset of shootouts which corroborates an advantage for the first shooter, albeit with a smaller effect than what has been documented in previous research. To evaluate the impact of alternative ordering of shots, we model shootouts as a probability network, calibrate it using the data from the traditional ordering, and use the model to conduct counterfactual analysis. Our results show that alternating the team that shoots first in each round would reduce the impact of ordering. These results were in part developed as supplement to field studies to support the International Football Association Board’s (IFAB) consideration of changing the shooting order.

BackgroundAdministrative data can be used to support research, such as in the UK Biobank. Hospital Episode Statistics (HES) are national data for England that include contain ICD-10 diagnoses for inpatient mental healthcare episodes, but the validity of these diagnoses for research purposes has not been assessed.Methods250 peoples' HES records were selected based on a HES recorded inpatient stay at the South London and Maudsley NHS Foundation Trust with a diagnosis of schizophrenia, a wider schizophrenia spectrum disorder, bipolar affective disorder or unipolar depression. A gold-standard research diagnosis was made using Clinical Records Interactive Search pseudonymised electronic patient records using, and the OPCRIT+ algorithm.ResultsPositive predictive value at the level of lifetime psychiatric disorder was 100%, and at the level of lifetime diagnosis in the four categories of schizophrenia, wider schizophrenia spectrum, bipolar or unipolar depression was 73% (68-79). Agreement varied by diagnosis, with schizophrenia having the highest PPV at 90% (80-96). Each person had an average of five psychiatric HES records. An algorithm that looked at the last recorded psychiatric diagnosis led to greatest overall agreement with the research diagnosis.DiscussionFor people who have a HES record from a psychiatric admission with a diagnosis of schizophrenia spectrum disorder, bipolar affective disorder or unipolar depression, HES records appear to be a good indicator of a mental disorder, and can provide a diagnostic category with reasonable certainty. For these diagnoses, HES records can be an effective way of ascertaining psychiatric diagnosis.