Tag: nevin manimala

Sleep. 2022 May 10:zsac109. doi: 10.1093/sleep/zsac109. Online ahead of print.

ABSTRACT

We investigated the potential role of sleep-trait associated genetic loci in conferring a degree of their effect via pancreatic α- and β- cells, given that both sleep disturbances and metabolic disorders, including type 2 diabetes and obesity, involve polygenic contributions and complex interactions. We determined genetic commonalities between sleep and metabolic disorders, conducting linkage disequilibrium genetic correlation analyses with publicly available GWAS summary statistics. Then we investigated possible enrichment of sleep-trait associated SNPs in promoter-interacting open chromatin regions within α- and β- cells, intersecting public GWAS reports with our own ATAC-seq and high-resolution promoter-focused Capture C data generated from both sorted human α-cells and an established human beta-cell line (EndoC-βH1). Finally, we identified putative effector genes physically interacting with sleep-trait associated variants in α- and EndoC-βH1cells running variant-to-gene mapping and establish pathways in which these genes are significantly involved. We observed that insomnia, short and long sleep – but not morningness – were significantly correlated with type 2 diabetes, obesity and other metabolic traits. Both the EndoC-βH1 and α-cells were enriched for insomnia loci (P=0.01; P=0.0076), short sleep loci (P=0.017; P=0.022) and morningness loci (P=2.2×10 -7; P=0.0016), while the α-cells were also enriched for long sleep loci (P=0.034). Utilizing our promoter contact data, we identified 63 putative effector genes in EndoC-βH1 and 76 putative effector genes in α-cells, with these genes showing significant enrichment for organonitrogen and organophosphate biosynthesis, phosphatidylinositol and phosphorylation, intracellular transport and signaling, stress responses and cell differentiation. Our data suggest that a subset of sleep-related loci confer their effects via cells in pancreatic islets.

PMID:35537191 | DOI:10.1093/sleep/zsac109

Am J Audiol. 2022 May 10:1-8. doi: 10.1044/2022_AJA-21-00181. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the impact of file compression on clinically measured word recognition scores obtained using the Northwestern University Test Number Six (NU-6; Auditec recording) materials.

METHOD: Participants were 86 adults (N = 170 ears; M _age = 65.5). The 25 most difficult words from each of four NU-6 test lists were used to measure word recognition. Two lists were compressed using a freely available Advanced Audio Coding compression algorithm and two were not. Word recognition was measured in each ear using one compressed file and one uncompressed file. Percent correct scores were calculated in each test condition and log transformed for analyses. Clinically meaningful differences between uncompressed and compressed scores were examined using 95% critical difference ranges. The effects of file compression on word recognition scores were examined in the context of multiple potential confounding effects, including age and degree of hearing loss, using linear mixed-effects models (LMMs).

RESULTS: Differences between compressed and uncompressed scores in a given ear exceeded the 95% critical difference range in about 7% of cases, approximating the 5% of expected cases occurring due to chance. Likewise, LMM results revealed no significant effect of file compression on clinically measured NU-6 word recognition scores and no significant interactions between compression effects and age or degree of hearing loss.

CONCLUSIONS: While the original uncompressed audio files are clearly the most appropriate stimuli for clinical purposes, our study results suggest that file compression, even at an aggressive 64 kilobits per second, does not have a statistically significant, or clinically meaningful, effect on word recognition scores when measured using these Auditec materials.

PMID:35537124 | DOI:10.1044/2022_AJA-21-00181

J ECT. 2022 Feb 3. doi: 10.1097/YCT.0000000000000820. Online ahead of print.

ABSTRACT

OBJECTIVE: Our study aimed to (1) examine the effect of adjunctive high-definition transcranial direct current stimulation (HD-tDCS) in craving and withdrawal among patients with opioid use disorder on buprenorphine-naloxone, and (2) examine effect of HD-tDCS changes in glutamate-glutamine and [gamma]-aminobutyric acid (GABA) at the left dorsolateral prefrontal cortex (DLPFC) among patients with opioid use disorder on buprenorphine-naloxone.

METHODS: This was a pilot randomized double-blind, sham-controlled parallel-group study. A total of 28 patients on buprenorphine-naloxone (6/1.5 mg/d) were randomly allocated into 2 groups for active and sham HD-tDCS stimulation. High-definition transcranial direct current stimulation was administered twice daily for consecutive 5 days, from days 2 to 6. The Clinical Opiate Withdrawal Scale (COWS), the Desire for Drug Questionnaire (DDQ), the Obsessive-Compulsive Drug Use Scale (OCDUS), and glutamate-glutamine and GABA at DLPFC via proton magnetic resonance spectroscopy were measured at baseline and on day 7.

RESULTS: Both active and sham groups had comparable changes in DDQ, OCDUS (except 2 subcomponents), COWS, and glutamate-glutamine and GABA at DLPFC. In the active HD-tDCS group, statistically significant reductions were observed in DDQ, OCDUS, and COWS but not in glutamate-glutamine and GABA.

CONCLUSIONS: The adjunctive active HD-tDCS group showed comparable changes in craving and withdrawal, and glutamate-glutamine and GABA at DLPFC compared with sham HD-tDCS. Craving and withdrawal but not glutamate-glutamine and GABA at DLPFC decreased significantly with adjunctive HD-tDCS. Future studies with larger sample size and online assessment of glutamate-glutamine and GABA would enhance our knowledge.

PMID:35537121 | DOI:10.1097/YCT.0000000000000820

JCO Glob Oncol. 2022 May;8:e2100425. doi: 10.1200/GO.21.00425.

ABSTRACT

PURPOSE: International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes.

METHODS: All patients with unilateral Wilms tumor (WT), age > 6 months, treated with preoperative chemotherapy as per protocol, and registered between 2001 and 2011 were eligible. Countries were grouped to give comparable case numbers and geographical representation. Cox univariable and multivariable (MVA) statistics were applied, with the German collaborative group (Gesellschaft für Pädiatrische Onkologie und Hämatologie-Austria, Germany, and Switzerland) as reference for hazard ratios for event-free survival (EFS) and overall survival (OS).

RESULTS: A total of 3,176 eligible patients were registered from 24 countries assigned into six groups. Age and histologic risk group distribution were similar across all groupings. The distribution of WT stage varied by country grouping, with 14.9% (range, 11.1%-18.2%) metastatic at diagnosis. Median follow-up was 78.9 months. For localized WT, 5-year EFS varied from 80% (Brazilian group) to 91% (French group; P < .0001), retaining significance only for Brazil in MVA (P = .001). Five-year OS varied from 89% (Brazilian group) to 98% (French group; P < .0001). In MVA, only superior OS in France was significant (P = .001). Five-year EFS/OS for stage IV did not vary significantly. High-risk histology and tumor volume at surgery were significantly associated with increased risk of death in MVA for metastatic disease.

CONCLUSION: International benchmarking of survival rates from WT within a large trial/study database has demonstrated statistically significant differences. Clinical interpretation should take account of variation in tumor stage but also treatment factors.

PMID:35537105 | DOI:10.1200/GO.21.00425

Ned Tijdschr Tandheelkd. 2022 May;129(5):219-222. doi: 10.5177/ntvt.2022.05.21120.

ABSTRACT

Stannous fluoride is one of the first fluoride compounds that were added to dentifrices. Besides the well-known effect of fluoride, the presence of tin could also have an effect on dental health by its anti-microbial activity and the ability to form insoluble metal salts. The functioning of stannous fluoride has been studied extensively in many scientific publications. On the basis of the available literature, the use of stannous fluoride instead of sodium fluoride could be advantageous in case of gingivitis, halitosis, dentine hypersensitivity, or erosion. The effects that were found are statistically significant, albeit rather small, which makes it harder to predict the actual gain in dental health or the clinical relevance for an individual patient.

PMID:35537088 | DOI:10.5177/ntvt.2022.05.21120

J Clin Oncol. 2022 May 10:JCO2102285. doi: 10.1200/JCO.21.02285. Online ahead of print.

ABSTRACT

Advances in biology and immunology have elucidated genetic and immunologic origins of cancer. Innovations in sequencing technologies revealed that distinct cancer histologies shared common genetic and immune phenotypic traits. Pharmacologic developments made it possible to target these alterations, yielding novel classes of targeted agents whose therapeutic potential span multiple tumor types. Basket trials, one type of master protocol, emerged as a tool for evaluating biomarker-targeted therapies among multiple tumor histologies. Conventionally conducted within the phase II setting and designed to estimate high and durable objective responses, basket trials pose challenges to statistical design and interpretation of results. This article reviews basket trials implemented in oncology studies and discusses issues related to their statistical design and analysis.

PMID:35537102 | DOI:10.1200/JCO.21.02285

Vet Med Sci. 2022 May 10. doi: 10.1002/vms3.835. Online ahead of print.

ABSTRACT

Bats are the natural reservoir host for many pathogenic and non-pathogenic viruses, potentially spilling over to humans and domestic animals directly or via an intermediate host. The ongoing COVID-19 pandemic is the continuation of virus spillover events that have taken place over the last few decades, particularly in Asia and Africa. Therefore, these bat-associated epidemics provide a significant number of hints, including respiratory cellular tropism, more intense susceptibility to these cell types, and overall likely to become a pandemic for the next spillover. In this systematic review, we analysed data to insight, through bat-originated spillover in Asia and Africa. We used STATA/IC-13 software for descriptive statistics and meta-analysis. The random effect of meta-analysis showed that the pooled estimates of case fatality rates of bat-originated viral zoonotic diseases were higher in Africa (61.06%, 95%CI: 50.26 to 71.85, l² % = 97.3, p < 0.001). Moreover, estimates of case fatality rates were higher in Ebola (61.06%; 95%CI: 50.26 to 71.85, l² % = 97.3, p < 0.001) followed by Nipah (55.19%; 95%CI: 39.29 to 71.09, l² % = 94.2, p < 0.001), MERS (18.49%; 95%CI: 8.19 to 28.76, l² % = 95.4, p < 0.001) and SARS (10.86%; 95%CI: 6.02 to 15.71, l² % = 85.7, p < 0.001) with the overall case fatality rates of 29.86 (95%CI: 29.97 to 48.58, l² % = 99.0, p < 0.001). Bat-originated viruses have caused several outbreaks of deadly diseases, including Nipah, Ebola, SARS and MERS in Asia and Africa in a sequential fashion. Nipah virus emerged first in Malaysia, but later, periodic outbreaks were noticed in Bangladesh and India. Similarly, the Ebola virus was detected in the African continent with neurological disorders in humans, like Nipah, seen in the Asian region. Two important coronaviruses, MERS and SARS, were introduced, both with the potential to infect respiratory passages. This paper explores the dimension of spillover events within and/or between bat-human and the epidemiological risk factors, which may lead to another pandemic occurring. Further, these processes enhance the bat-originated virus, which utilises an intermediate host to jump into human species.

PMID:35537080 | DOI:10.1002/vms3.835

Ann Am Thorac Soc. 2022 May 10. doi: 10.1513/AnnalsATS.202201-085OC. Online ahead of print.

ABSTRACT

RATIONALE: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking.

OBJECTIVES: In this study we provide evidence that blood platelets contain a distinctive RNA profile that may be exploited for detection of pulmonary hypertension.

METHODS: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 controls clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer cDNA amplification, and sequenced on the Illumina HiSeq platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by ANOVA-statistics. A particle swarm optimisation (PSO)-enhanced classification algorithm was built employing a development (n=213 samples) and independent validation series (n=159 samples).

RESULTS: We detected a total of 4014 different RNAs in blood platelets from pulmonary hypertension patients (n=177) and asymptomatic controls (n=195). GSEA gene ontology analysis revealed enriched RNA levels for genes related to RNA-processing, translation and mitochondrial function. A PSO-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95%CI 0.83-0.93) area under the curve and a negative predictive value of 91% in the independent validation series. Prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anti-coagulants.

CONCLUSION: A platelet RNA-panel may accurately discriminate patients with pulmonary hypertension from asymptomatic controls. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test, to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension.

PMID:35537078 | DOI:10.1513/AnnalsATS.202201-085OC

Milbank Q. 2022 May 10. doi: 10.1111/1468-0009.12568. Online ahead of print.

ABSTRACT

Policy Points Looking for a way to curtail market power abuses in health care and rein in prices, 20 states have restricted most-favored-nation (MFN) clauses in some health care contracts. Little is known as to whether restrictions on MFN clauses slow health care price growth. Banning MFN clauses between insurers and hospitals in highly concentrated insurer markets seems to improve competition and lead to lower hospital prices.

CONTEXT: Most-favored-nation (MFN) contract clauses have recently garnered attention from both Congress and state legislatures looking for ways to curtail market power abuses in health care and rein in prices. In health care, a typical MFN contract clause is stipulated by the insurer and requires a health care provider to grant the insurer the lowest (i.e., the most-favored) price among the insurers it contracts with. As of August 2020, 20 states restrict the use of MFN clauses in health care contracts (19 states ban their use in at least some health care contracts), with 8 states prohibiting their use between 2010 and 2016.

METHODS: Using event study and difference-in-differences research designs, we compared prices for a standardized hospital admission in states that banned MFN clauses between 2010 and 2016 with standardized hospital admission prices in states without MFN bans.

FINDINGS: Our results show that bans on MFN clauses reduced hospital price growth in metropolitan statistical areas (MSAs) with highly concentrated insurer markets. Specifically, we found that mean hospital prices in MSAs with highly concentrated insurer markets would have been $472 (2.8%) lower in 2016 had the MSAs been in states that banned MFN clauses in 2010. In 2016, the population in our sample that resided in MSAs with highly concentrated insurer markets was just under 75 million (23% of the US population). Hence, banning MFN clauses in all MSAs in our sample with highly concentrated insurer markets in 2010 would have generated savings on hospital expenditures in the range of $2.4 billion per year.

CONCLUSIONS: Our empirical findings suggest banning MFN clauses between insurers and providers in highly concentrated insurer markets would improve competition and lead to lower prices and expenditures.

PMID:35537077 | DOI:10.1111/1468-0009.12568

JMIR Diabetes. 2022 Apr 6. doi: 10.2196/37882. Online ahead of print.

ABSTRACT

BACKGROUND: In South Africa, diabetes is a leading cause of morbidity and mortality, which was exacerbated during the coronavirus pandemic. Most education and counselling was stopped during lockdown and the Great4Diabetes WhatsApp Chatbot was innovated to fill this gap.

OBJECTIVE: To evaluate the implementation of the Chatbot in Cape Town, South Africa, between May and October 2021.

METHODS: Convergent mixed methods evaluated implementation outcomes: acceptability, adoption, appropriateness, feasibility, fidelity, cost, coverage, effects and sustainability. Quantitative data was derived from the Chatbot and analysed with the Statistical Package for Social Sciences. Qualitative data was collected from key informants in the health services, Aviro Health and Stellenbosch University and analysed using the framework method, assisted by Atlas-ti. The Chatbot provided users with 16 voice messages and graphics, in English, Afrikaans or Xhosa. Messages focused on coronavirus and self-management of type-2 diabetes. Users had to reply to a question after each message to receive the next message and give brief feedback at the end of the programme.

RESULTS: The Chatbot was adopted by the Metro Health Services to assist people with diabetes who had restricted health care during lockdown and yet were more at risk of hospitalisation and death from coronavirus. The Chatbot was disseminated via healthcare workers in primary care facilities and local non-profit organisation as well as via local media and television. Two technical glitches interrupted the dissemination, but did not substantially affect user behaviour. Minor changes were made to the Chatbot to improve its utility for users. Many patients had access to a smartphone and were able to use the Chatbot via WhatsApp. Overall 8158 people connected with the Chatbot and 4577 (56.1%) proceeded to listen to the messages, with 12.6% of them listening to all 16 messages, mostly within 32 days. Incremental set-up costs were $5295 and operational costs over 6-months were $17304. More than 90% of users that listened to each message found them useful. Of the 533 that completed the whole programme 71.1% said they changed their self-management “a lot” and 87.6% were more confident. Most users changed their lifestyle in terms of diet (76.1%) and physical activity (53.6%). Healthcare workers also saw the benefits to patients and recommended the service continue. Sustainability of the Chatbot will depend on the future policy of the provincial Department of Health towards mHealth and willingness to contract with Aviro Health. There is potential to go to scale and include other languages and chronic conditions.

CONCLUSIONS: The Chatbot shows great potential to complement traditional health care approaches for people with diabetes and assist with more comprehensive patient education. Further research is needed to fully explore the patient’s experience of the Chatbot and to evaluate the effectiveness in our context.

CLINICALTRIAL: NA.

PMID:35537057 | DOI:10.2196/37882