Category: Nevin Manimala

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

J Med Internet Res. 2022 May 6. doi: 10.2196/27310. Online ahead of print.

ABSTRACT

BACKGROUND: Studies suggest diurnal patterns of occurrence of some eye conditions. Leveraging new information sources such as online search data to learn more about such patterns could improve understanding of patient eye-related conditions and well-being, better inform timing of clinical and remote eye care, and improve precision when targeting online public health campaigns towards underserved populations.

OBJECTIVE: To investigate our hypothesis that the public is likely to consistently search about different ophthalmologic conditions at different hours of the day or days of week, we conducted an observational study using search data for terms related to ophthalmologic conditions such as conjunctivitis. We assessed whether search volumes reflected diurnal or day-of-week patterns and if those patterns were distinct from each other.

METHODS: Design: Hourly search data for eye-related and control search terms were analyzed and compared using time series regression models with trend and periodicity terms to remove outliers and then estimate diurnal effects. Setting: Google Trends data from 10 USA states for the entire year of 2018. Exposure: Internet search. Participants: Populations that searched Google’s search engine using our chosen study terms. Main Outcome Measures: Cyclical hourly and day of week online search patterns. For statistical analyses P < .001 was considered statistically significant.

RESULTS: Distinct diurnal (P < .001 for all search terms) and day-of-week search patterns for eye-related terms were observed but with differing peak time periods and cyclic strengths. Some diurnal patterns represented those reported from prior clinical studies. Of the eye related terms, “pink eye” showed the largest diurnal amplitude-to-mean ratios. Stronger signal was restricted to and peaked in mornings, and amplitude was higher on weekdays. In contrast, “dry eyes” had a higher amplitude diurnal pattern on weekends, with stronger signal occurring over a broader evening to morning period and peaking in early morning.

CONCLUSIONS: The frequency of online searches for various eye conditions can show cyclic patterns according to time of day or week. Further studies to understand the reasons for these variations may help supplement current clinical understanding of ophthalmologic symptom presentation and improve the timeliness of patient messaging and care interventions.

CLINICALTRIAL: Not applicable.

PMID:35537041 | DOI:10.2196/27310

Science. 2022 May 6;376(6593):563-564. doi: 10.1126/science.abq8309. Epub 2022 May 5.

ABSTRACT

Agency wants to retool its surveys and decennial census to improve efficiency and generate better data.

PMID:35536907 | DOI:10.1126/science.abq8309

J Pediatr Hematol Oncol. 2022 May 4. doi: 10.1097/MPH.0000000000002480. Online ahead of print.

ABSTRACT

Sarcomas with BCOR alteration are a heterogenous group characterized by changes including internal tandem duplications (ITDs) and recurring fusions with CCNB3, ZC3H7B, and other rare partners. With widespread genomic testing, these alterations are now associated with histologies such as Ewing-like sarcoma (BCOR::CCNB3), high-grade endometrial stromal sarcoma (ZC3H7B::BCOR), and clear cell sarcoma of kidney (BCOR-ITD). BCOR altered sarcomas of soft tissues and organs were identified through PubMed using keywords “Sarcoma (AND) BCOR” from 2005 through October 2021. Summary statistics and outcome data were calculated using STATA v12.1. Forty-one publications described 190 patients with BCOR altered soft tissue or organ sarcomas. BCOR-ITD was most common, followed by BCOR::CCNB3, ZC3H7B::BCOR. BCOR-ITD tumors occurred mainly in infants, BCOR::CCNB3 commonly occurred in adolescent young adults, and ZC3H7B::BCOR only in adults. The most common site for BCOR::CCNB3 fused tumors was extremity, BCOR-ITD kidney and ZC3H7B::BCOR uterus. Metastasis was rare in patients with BCOR::CCNB3. While most underwent resection and chemotherapy, few received radiation. Median follow-up of survivors was 24 months. Five year overall survival for patients with BCOR::CCNB3 fusions was 68% (95% confidence interval [CI]: 46%-83%). Patients with BCOR-ITD and ZC3H7B::BCOR had worse prognoses with 5 years overall survival of 35% (95% CI: 15%-56%) and 41% (95% CI: 11%-71%), respectively, demonstrating need for collaborative efforts identifying optimal treatments to improve outcomes.

PMID:35537005 | DOI:10.1097/MPH.0000000000002480

Cancer Res. 2022 May 10:canres.2395.2021. doi: 10.1158/0008-5472.CAN-21-2395. Online ahead of print.

ABSTRACT

Identifying biomarkers predictive of cancer cell response to drug treatment constitutes one of the main challenges in precision oncology. Recent large-scale cancer pharmacogenomic studies have opened new avenues of research to develop predictive biomarkers by profiling thousands of human cancer cell lines at the molecular level and screening them with hundreds of approved drugs and experimental chemical compounds. Many studies have leveraged these data to build predictive models of response using various statistical and machine learning methods. However, a common pitfall to these methods is the lack of interpretability as to how they make predictions, hindering the clinical translation of these models. To alleviate this issue, we used the recent logic modeling approach to develop a new machine learning pipeline that explores the space of bimodally expressed genes in multiple large in vitro pharmacogenomic studies and builds multivariate, nonlinear, yet interpretable logic-based models predictive of drug response. The performance of this approach was showcased in a compendium of the three largest in vitro pharmacogenomic data sets to build robust and interpretable models for 101 drugs that span 17 drug classes with high validation rates in independent datasets. These results along with in vivo and clinical validation, support a better translation of gene expression biomarkers between model systems using bimodal gene expression.

PMID:35536872 | DOI:10.1158/0008-5472.CAN-21-2395