Tag: statistics

Nature. 2021 May 12. doi: 10.1038/s41586-021-03606-z. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has seen digital contact tracing emerge around the world to help prevent spread of the disease. A mobile phone app records proximity events between app users, and when a user tests positive for COVID-19, their recent contacts can be notified instantly. Theoretical evidence has supported this new public health intervention^1-6, but its epidemiological impact has remained uncertain⁷. Here we investigated the impact of the NHS COVID-19 app for England and Wales, from its launch on 24 September 2020 through to the end of December 2020. It was used regularly by approximately 16.5 million users (28% of the total population), and sent approximately 1.7 million exposure notifications: 4.4 per index case consenting to contact tracing. We estimated that the fraction of app-notified individuals subsequently showing symptoms and testing positive (the secondary attack rate, SAR) was 6.0%, comparable to the SAR for manually traced close contacts. We estimated the number of cases averted by the app using two complementary approaches. Modelling based on the notifications and SAR gave 284,000 (108,000-450,000), and statistical comparison of matched neighbouring local authorities gave 594,000 (317,000-914,000). Roughly one case was averted for each case consenting to notification of their contacts. We estimated that for every percentage point increase in app users, the number of cases can be reduced by 0.8% (modelling) or 2.3% (statistical analysis). These findings provide evidence for continued development and deployment of such apps in populations that are awaiting full protection from vaccines.

PMID:33979832 | DOI:10.1038/s41586-021-03606-z

Z Gastroenterol. 2021 May;59(5):423-437. doi: 10.1055/a-1404-3344. Epub 2021 May 12.

ABSTRACT

BACKGROUND: Okoubaka aubrevillei is used in traditional West African medicine and in homeopathy for treatment and prevention of several gastrointestinal problems. The aim of this in vitro study was to evaluate the effect of repeated doses of two Okoubaka products (10 % ethanolic tincture, mother tincture (MT); 3^rd decimal potency, 3X) on the microbial activity of physiological human colon microbiota using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) and to investigate any preventive effect against infections with diarrhea-causing pathogens.

METHODS: Upon inoculation with fecal microbiota from a healthy donor, 4 parallel proximal colon compartments of the SHIME were treated either with Okoubaka MT, Okoubaka 3X, ethanol control or blank control for 7 days. Using the Okoubaka-adapted microbial community from SHIME, 48 h challenge tests were performed with enterotoxigenic Escherichia coli (ETEC) and Salmonella enteritidis in 4 different doses (10³-10⁸ colony forming units as typical in vivo infectious doses). Pathogen concentrations, short-chain fatty acids (SCFAs) and branched SCFA production were measured in triplicate at 0, 24 and 48 h.

RESULTS: In the challenge tests, both Okoubaka products were able to restrict the colonization of ETEC and Salmonella at 3 of the 4 pathogen doses (except the highest doses), with a stronger anti-pathogenic effect for MT, which included a reduction of 2.0 log-units of ETEC (p < 0.0001) and 1.1 log-units of Salmonella (p < 0.0001). Total SCFA levels remained unaffected, but butyrate increased during the first 24 h (p < 0.0001 for ETEC), accompanied by decreased acetate production.

CONCLUSION: We observed in vitro a systemic activating effect of Okoubaka on intestinal microbiome resistance, which resulted in an anti-pathogenic effect, especially against ETEC. We hypothesize that the mode of action in vivo is also based on systemic regulative effects.

PMID:33979845 | DOI:10.1055/a-1404-3344

Pharmacopsychiatry. 2021 May 12. doi: 10.1055/a-1478-4574. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite the ethnic differences in 5-HTTLPR (S allele relates to better antidepressant response in Korean and Japanese people, while L allele with better response in Caucasians), it is unclear whether 5-HTTLPR and its high expression locus rs25531 are interactively associated with antidepressant treatment outcome. We investigated the individual and interaction effects of these polymorphisms on antidepressant treatment outcomes in the Korean population.

METHODS: A total of 464 Korean subjects with major depressive disorder completed 6 weeks of antidepressant monotherapy. Venous blood was extracted for genotyping 5-HTTLPR and rs25531 by polymerase chain reaction and DNA sequencing. We used logistic regression analyses to verify the main and interaction effects of 5-HTTLPR and rs25531 on response and remission after antidepressant treatment.

RESULTS: After adjusting for covariates, the SS genotype of 5-HTTLPR was significantly associated with better treatment outcomes (p<0.001, odds ratio [OR] [95% confidence interval (CI)]=2.435 [1.551, 3.823] in response; p<0.001, OR [95% CI]=2.912 [1.730, 4.903] in remission), while G-containing genotype (AG+GG) of rs25531 was only associated with remission (p=0.034, OR [95% CI]=2.104 [1.058, 4.181]). The interaction effect of 5-HTTLPR and rs25531 on response and remission was insignificant (all p>0.05).

DISCUSSION: Our findings suggest variations in allelic frequency and functionality of 5-HTTLPR and rs25531 among the different ethnicities. We found a minor advantage of rs25531 in achieving remission. However, there was no interaction effect with 5-HTTLPR.

PMID:33979867 | DOI:10.1055/a-1478-4574

Gerontology. 2021 May 12:1-9. doi: 10.1159/000516077. Online ahead of print.

ABSTRACT

OBJECTIVE: Longitudinal studies investigating the link between social support and functional decline are limited among the oldest old. Thus, the aim of this study was to examine whether changes in social support are associated with functional decline among the oldest old longitudinally using panel regression models.

METHODS: Longitudinal data from 3 waves (waves 7, 8, and 9) of a multicenter prospective cohort study covering primary care patients aged ≥85 years were used. In the analytical sample, n equaled 624 individuals. The validated Lawton and Brody Instrumental Activities of Daily Living (IADL) scale and the well-established Barthel Index (ADL) were used to quantify functional status. The psychometrically sound Lubben Social Network Scale was used to measure social support. Several potential confounders such as age, marital status, cognitive decline, or depressive symptoms were included in the fixed effects (FE) regression models.

RESULTS: Linear FE regressions showed that a decrease in social support is associated with functional decline (IADL: β = 0.03, p < 0.05; ADL: β = 0.27, p < 0.05) in men but not in women. With IADL as outcome measure, the interaction term (sex × social support) achieved statistical significance (p < 0.01). With regard to covariates, functional decline (IADL and ADL) was consistently associated with increasing age, an increase in the number of chronic conditions (except for women [ADL]), and cognitive decline (except for men [ADL]). Furthermore, functional decline (ADL) was associated with an increase in depressive symptoms.

DISCUSSION: Our findings highlight the meaning of social support for functional status among the oldest old. Finding ways to sustain social support in highest age may be a promising approach in order to postpone functional decline.

PMID:33979796 | DOI:10.1159/000516077

Adv Skin Wound Care. 2021 Jun 1;34(6):314-320. doi: 10.1097/01.ASW.0000744340.11915.93.

ABSTRACT

OBJECTIVE: To analyze the content, reliability, and quality of the most viewed YouTube videos targeting patients with ostomies intending to learn about ostomy care (OC).

METHODS: Using the keywords “stoma care,” “colostomy care,” and “ileostomy care,” researchers assessed the publicly visible English-language ostomy patient education videos available on YouTube. A total of 84 videos were independently analyzed by two physicians experienced in OC. Data on video characteristics, source, content, reliability, and quality were collected and recorded for each video separately.

RESULTS: Of the 84 videos analyzed, 49 were classified as useful (58.33%) and 35 as misleading (41.66%). There were statistically significant differences between the groups in terms of the time elapsed since upload (P < .017), reliability (P < .001), comprehensiveness (P < .001), Global Quality Scale scores (P < .001), source (P < .001), and lecturer types (P < .011). The reliability, comprehensiveness, and Global Quality Scale scores were statistically higher for videos uploaded by universities, professional healthcare communities, and nonprofit physicians (P < .001). However, the popularity of the OC videos posted on YouTube was not related to their reliability, comprehensiveness, or quality.

CONCLUSIONS: The open-access nature of the YouTube platform may impair patient education video quality and accuracy. YouTube may be an additional educational tool for OC, but clinicians need to be familiar with specific and reliable resources to guide and educate new patients with ostomies to achieve the best outcomes.

PMID:33979820 | DOI:10.1097/01.ASW.0000744340.11915.93

Psychiatry Res. 2021 Apr 30;301:113974. doi: 10.1016/j.psychres.2021.113974. Online ahead of print.

ABSTRACT

Effective posttraumatic stress disorder (PTSD) pharmacotherapy is needed. This 12-week randomized multicenter trial evaluated efficacy and safety of TNX-102 SL, a bedtime sublingual formulation of cyclobenzaprine, in patients with military-related PTSD randomized to TNX-102 SL 2.8 mg or 5.6 mg, or placebo. Primary analysis comparing change from baseline in Clinician-Administered PTSD Scale-5 score between 2.8 mg (n=90) and placebo (n=92) was not significant. Secondary analysis of 5.6 mg (n=49) vs placebo demonstrated a mean difference of -4.5 units, p=.05, or, accounting for missing data by multiple imputation, -5.0 units, p=.03. Clinician Global Impression – Improvement responder rate was greater in 5.6 mg than placebo (p=0.04), as was mean functional improvement in Sheehan Disability Scale social domain (p=.03) and trended in work domain (p=.05). Post-hoc analyses showed early sleep improvement predicted improvement in PTSD after 12 weeks for TNX-102 SL (p<.01), not for placebo. Most common administration site reaction in TNX-102 SL groups was oral hypoaesthesia (5.6 mg, 36%; 2.8 mg, 39%; placebo, 2%), while most common systemic adverse event was somnolence (5.6 mg, 16%; 2.8 mg, 12%; placebo, 6%). This provides preliminary evidence that TNX-102 SL 5.6 mg reduces PTSD symptoms, improves sleep and psychosocial function, and is well tolerated. Clinicaltrials.gov Identifier: NCT02277704.

PMID:33979763 | DOI:10.1016/j.psychres.2021.113974

Mult Scler Relat Disord. 2021 Apr 25;52:102972. doi: 10.1016/j.msard.2021.102972. Online ahead of print.

ABSTRACT

BACKGROUND: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS.

METHODS: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.

RESULTS: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI.

CONCLUSION: In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

PMID:33979770 | DOI:10.1016/j.msard.2021.102972

Kidney Blood Press Res. 2021 May 12:1-6. doi: 10.1159/000516206. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyponatraemia is associated with increased mortality in patients undergoing maintenance haemodialysis. In anuric patients, hyponatraemia development depends on the water-sodium ratio in retained fluid within the interdialysis interval (IDI).

OBJECTIVE: This study aimed to calculate the retained sodium-retained water ratio in patients on maintenance haemodialysis and make a differential diagnosis of hyponatraemia according to these data.

METHODS: The amount of retained water was determined as body weight gain (ΔBW) within the IDI. Sodium retention was calculated using our formula: eRNa+ = ΔBW × (SNa+)t2 – total body water (TBW)t1 × ([SNa+]t1 – [SNa+]t2), where TBW represents the calculated volume of the total body water and (SNa+)t1 and (SNa+)t2 represent the sodium concentration at the beginning and at the end of the IDI, respectively. We performed 89 measurements in 32 anuric patients on maintenance haemodialysis.

RESULTS: Hyponatraemia was detected in 13 measurements at the end of the IDI. The ΔBW had no statistically significant difference between normonatraemic and hyponatraemic patients. Hyponatraemic patients had significantly lower levels of retained sodium. The retained water–retained sodium ratio facilitated in differentiating dilution hyponatraemia, nutritional hyponatraemia, depletion hyponatraemia, and dilution hyponatraemia associated with sodium wasting or malnutrition.

CONCLUSION: The composition of retained fluid during the IDI may be hypotonic, hypertonic, or isotonic in relation to the extracellular fluid. Most of the hyponatraemic patients had hypotonic fluid retained during the IDI because of dilution as well as gastrointestinal sodium loss and/or malnutrition.

PMID:33979795 | DOI:10.1159/000516206

Acta Trop. 2021 May 9:105951. doi: 10.1016/j.actatropica.2021.105951. Online ahead of print.

ABSTRACT

OBJECTIVE: This study pursues three main objectives: 1) exploring the spatial distribution patterns of human brucellosis (HB); 2) identifying parameters affecting the disease spread; and 3) modeling and predicting the spatial distribution of HB cases in 2012-2016 and 2017-2018, respectively, in rural districts of Mazandaran province, Iran.

METHODS: We collected data on the disease incidence, demography, ecology, climate, topography, and vegetation. Using the Global Moran’s I statistic, we measured spatial autocorrelation between log (number of HB cases). We applied the Getis-Ord G_i^* statistic to identify areas with high and low risk of the disease. To investigate the relationships between the factors affecting the incidence of HB as input variables together and the factors with the log (number of HB cases) as an output variable, we used the statistical linear regression model and the Pearson correlation coefficient. Then, we implemented a GIS-based adaptive neuro-fuzzy inference system (ANFIS) with two subtractive clustering and fuzzy c-means (FCM) clustering methods to model and predict the spatial distribution of HB.

RESULTS: Global Moran’s I spatial autocorrelation analysis indicated that the type of HB distribution is clustered in all years except 2014 and 2017, which are random. According to the Getis-Ord G_i^* analysis, the location of the hot spots varied during 2012-2018. In 2012 and 2013, most of the hot spots were seen in the west of the province. While in 2018, they were mostly concentrated in the eastern regions of the province. The linear regression model indicated that the parameters affecting the incidence of HB are independent of each other and can explain only 25.3% of the total changes in the log (number of HB cases). The results of the Pearson correlation coefficient showed that there were positive relationships between vegetation, log (population), and the number of sheep and cattle (P-value < 0.05). The above-mentioned factors had the strongest positive correlation with the log (number of HB cases) (P-value < 0.01). These results may be due to the fact that vegetation regions are suitable for livestock grazing, attracting large crowds of people. Therefore, this will increase HB cases. We compared the results of subtractive clustering and FCM clustering methods by evaluation criteria (e.g., linear correlation coefficient (LCC) and mean absolute error (MAE)) in two phases of development and assessment of the ANFIS model. In the evaluation phase, we predicted the spatial distribution of log (number of HB cases) in 2017 and 2018 for subtractive clustering (R² = 0.699, LCC or R = 0.692, MAE = 0.509, MSE = 0.455) and for FCM clustering (R² = 0.704, LCC or R = 0.697, MAE = 0.512, MSE = 0.448) that showed FCM clustering outperformed the subtractive clustering.

CONCLUSION: The findings may have important implications for public health. The emergence of the hot spots in the east of the province can be a warning to the health system. Health authorities can use the findings of this study to predict the spread of HB and perform HB prevention programs. They can also investigate the factors affecting the prevalence of the disease, identify high-risk areas, and ultimately allocate resources to high-risk regions.

PMID:33979640 | DOI:10.1016/j.actatropica.2021.105951

J Clin Epidemiol. 2021 May 9:S0895-4356(21)00140-2. doi: 10.1016/j.jclinepi.2021.04.017. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the impact of guidance and training on the inter-rater reliability (IRR), inter-consensus reliability (ICR) and evaluator burden of the Risk of Bias (RoB) in Non-randomized Studies (NRS) of Interventions (ROBINS-I) tool, and the RoB instrument for NRS of Exposures (ROB-NRSE).

STUDY DESIGN AND SETTING: In a before-and-after study, seven reviewers appraised the RoB using ROBINS-I (n=44) and ROB-NRSE (n=44), before and after guidance and training. We used Gwet’s AC₁ statistic to calculate IRR and ICR.

RESULTS: After guidance and training, the IRR and ICR of the overall bias domain of ROBINS-I and ROB-NRSE improved significantly; with many individual domains showing either a significant (IRR and ICR of ROB-NRSE; ICR of ROBINS-I), or nonsignificant improvement (IRR of ROBINS-I). Evaluator burden significantly decreased after guidance and training for ROBINS-I, whereas for ROB-NRSE there was a slight nonsignificant increase.

CONCLUSION: Overall, there was benefit for guidance and training for both tools. We highly recommend guidance and training to reviewers prior to RoB assessments and that future research investigate aspects of guidance and training that are most effective.

PMID:33979663 | DOI:10.1016/j.jclinepi.2021.04.017