Search

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to 80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

BackgroundThe prevalence of diabetes in West Africa is increasing, posing a major public health threat. An estimated 24 million Africans have diabetes, with rates in West Africa around 2-6% and projected to rise 129% by 2045 according to the WHO. Over 90% of cases are Type 2 diabetes (IDF, World Bank). As diabetes is ambulatory care sensitive, good primary care is crucial to reduce complications and mortality. However, research on factors influencing diabetes primary care access, utilisation and quality in West Africa remains limited despite growing disease burden. While research has emphasised diabetes prevalence and risk factors in West Africa, there remains limited evidence on contextual influences on primary care. This scoping review aims to address these evidence gaps.Methods and analysisUsing the established methodology by Arksey and O'Malley, this scoping review will undergo six stages. The review will adopt the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR) guidelines to ensure methodological rigour. We will search four electronic databases and search through grey literature sources to thoroughly explore the topic. The identified articles will undergo thorough screening. We will collect data using a standardised data extraction form that covers study characteristics, population demographics, and study methods. The study will identify key themes and sub-themes related to primary healthcare access, utilisation, and quality. We will then analyse and summarise the data using a narrative synthesis approach.ResultsThe findings and conclusive report will be finished and sent to a peer-reviewed publication within six months.ConclusionThis review protocol aims to systematically examine and assess the factors that impact the access, utilisation, and standard of primary healthcare services for diabetes in West Africa.

IntroductionAny type of activity that results in caloric expenditure has the potential to reduce the risk of cardiovascular diseases; nonetheless, most people, especially office workers, are physically inactive. This study sought to evaluate the extent of physical inactivity and its determinants among the staff of selected banks in Accra, Ghana.MethodsThis was a cross-sectional study involving 219 banking staff randomly selected from five commercial banking institutions in Accra, Ghana. Demographic data was collected with a structured questionnaire. Physical inactivity was assessed using the Global Physical Activity Questionnaire. Study associations were determined using univariate analysis, and multivariate logistic regression models with adjusted odds ratio (AOR) and 95% confidence intervals (CI) estimated.ResultsTwo hundred and nineteen (219) participants were recruited, out of which 56.6% were males and 43.4% were females. The mean age (± SD) of the participants was 40.0±7.9 years. Physical inactivity was observed in 179 (81.7%) participants. The following were independently associated with physical inactivity: travel-related activities (AOR, 0.151; 95% CI, 0.059-0.384; pConclusionPhysical inactivity was very high among bankers. Travel-related activities reduced physical inactivity whiles working at the bank for more than six years increased physical inactivity. Thus, promoting regular physical activity, frequent monitoring, and implementation of other appropriate healthy lifestyle intervention strategies are vital to reduce risk of early onset disease conditions associated with physical inactivity in this population.

BackgroundThere is no effective therapy for the severe acute respiratory syndrome by coronavirus 2 (SARS-CoV2) responsible for the Coronavirus disease 2019 (Covid-19). To date, dexamethasone has shown a decrease in mortality in patients who require oxygen, especially those with invasive mechanical ventilation. However, it is unknown if another corticosteroid can be used, the optimal dose and its duration, to achieve a better clinical outcome. The objective of the study was to compare the differences in clinical outcome and laboratory results in hospitalized patients with severe SARS-CoV2 Pneumonia treated with dexamethasone at 6 mg doses versus patients treated with high-dose methylprednisolone.Materials and methodsAmbispective cohort study with survival analysis of 216 patients diagnosed with severe Covid-19 pneumonia confirmed by polymerase chain reaction for SARS-CoV2 by Berlin protocol, who were hospitalized in a high-complexity clinic in Medellín, Colombia. The patients should also have supplementary oxygen and radiological confirmation of Pneumonia by chest tomography. Sample size was not calculated since the total population that met the inclusion criteria was evaluated. 111 patients were treated with the institutional protocol with intravenous dexamethasone 6 mg QD for seven to 10 days if they required oxygen. Since September 15, 2020, the hospitalization protocol of the clinic was modified by the Infectious Diseases and Pulmonology service, recommending a high dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral prednisone 50 mg every day for 14 days. The protocol was not applied in the intensive care unit, where dexamethasone continued to be administered. The clinical outcome and differences in laboratory results of the patients who received dexamethasone vs. the prospective cohort that received methylprednisolone from September 15 to October 31, 2020, were evaluated. Follow-up was carried out by outpatient consultation one month after discharge or by telephone, inquiring about readmission or living-dead status.Results216 patients had Covid-19 pneumonia documented by ground-glass imaging and alveolar pressure / inspired oxygen fraction (PaFi) less than 300. 111 patients received dexamethasone (DXM) and 105 received methylprednisolone (MTP). Patients in the DXM group evolved to severe ARDS in a higher proportion (26.1% vs 17.1% than the MTP group). Upon completion 4 days of treatment with parenteral corticosteroid, laboratory markers of severity decreased significantly in the group that received MTP, CRP 2.85 (2.3-3.8) vs 7.2 (5.4-9.8), (p-value < 0.0001), D-dimer 691 (612-847) vs 1083 (740-1565) (p-value = 0.04) and DHL 273 (244-289) vs 355 (270.6-422) (p-value = 0.01). After starting the corticosteroid, transfer to the intensive care unit (4.8% vs. 14.4%) and mortality (9,5% vs. 17.1%) was lower in the group that received MTP. Recovery time was shorter in patients treated with MTP, three days (3-4) vs. DXM 6 days (5-8) (p-value < 0.0001). At 30-day follow-up, 88 (92.6%) were alive in MTP vs 58 (63.1%) of those who received dexamethasone.ConclusionsIn this study, the treatment of severe Covid-19 Pneumonia with high-dose methylprednisolone for three days followed by oral prednisone for 14 days, compared with 6 mg dexamethasone for 7 to 10 days, statistically significantly decreased the recovery time, the need for transfer to intensive care and the severity markers C-reactive protein (CRP), D-dimer and LDH. Randomized controlled studies with methylprednisolone are required to corroborate its effect, and studies in a population hospitalized in intensive care wards.

IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality-HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not-OR of 0.26 (95% CI: 0.06, 1.09).ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care.

The accumulation of knowledge required to produce economic value is a process that often relates to nations economic growth. Some decades ago many authors, in the absence of other available indicators, used to rely on certain measures of human capital such as years of schooling, enrollment rates, or literacy. In this paper, we show that the predictive power of years of education as a proxy for human capital started to dwindle in 1990 when the schooling of nations began to be homogenized. We developed a structural equation model that estimates a metric of human capital that is less sensitive than average years of education and remains as a significant predictor of economic growth when tested with both cross-section data and panel data.

This work presents a nonparametric statistical test, S-maup, to measure the sensitivity of a spatially intensive variable to the effects of the Modifiable Areal Unit Problem (MAUP). To the best of our knowledge, S-maup is the first statistic of its type and focuses on determining how much the distribution of the variable, at its highest level of spatial disaggregation, will change when it is spatially aggregated. Through a computational experiment, we obtain the basis for the design of the statistical test under the null hypothesis of non-sensitivity to MAUP. We performed an exhaustive simulation study for approaching the empirical distribution of the statistical test, obtaining its critical values, and computing its power and size. The results indicate that, in general, both the statistical size and power improve with increasing sample size. Finally, for illustrative purposes, an empirical application is made using the Mincer equation in South Africa, where starting from 206 municipalities, the S-maup statistic is used to find the maximum level of spatial aggregation that avoids the negative consequences of the MAUP.

BACKGROUND: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear. METHODS: A systematic review was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ASCO meeting abstracts up to May 2013 to identify randomized controlled trials that included advanced pancreatic cancer comparing the following regimens: G, G+5-fluorouracil, G+ capecitabine, G+S1, G+ cisplatin, G+ oxaliplatin, G+ erlotinib, G+ nab-paclitaxel, and FOLFIRINOX. Overall survival and progression-free survival with 95% credible regions were extracted using the Parmar method. A Bayesian multiple treatment comparisons was performed to compare all regimens simultaneously. RESULTS: Twenty-two studies were identified and 16 were included in the meta-analysis. Median overall survival, progression free survival, and response rates for G arms from all trials were similar, suggesting no significant clinical heterogeneity. For overall survival, the mixed treatment comparisons found that the probability that FOLFIRINOX was the best regimen was 83%, while it was 11% for G+ nab-paclitaxel and 3% for G+ S1 and G+ erlotinib, respectively. The overall survival hazard ratio for FOLFIRINOX versus G+ nab-paclitaxel was 0.79 [0.50-1.24], with no obvious difference in toxicities. The hazard ratios from direct pairwise comparisons were consistent with the mixed treatment comparisons results. CONCLUSIONS: FOLFIRINOX appeared to be the best regimen for advanced pancreatic cancer probabilistically, with a trend towards improvement in survival when compared with other regimens by indirect comparisons.

Rab monomeric GTPases regulate specific aspects of vesicle transport in eukaryotes including coat recruitment, uncoating, fission, motility, target selection and fusion. Moreover, individual Rab proteins function at specific sites within the cell, for example the ER, golgi and early endosome. Importantly, the localization and function of individual Rab subfamily members are often conserved underscoring the significant contributions that model organisms such as Caenorhabditis elegans can make towards a better understanding of human disease caused by Rab and vesicle trafficking malfunction. With this in mind, a bioinformatics approach was first taken to identify and classify the complete C. elegans Rab family placing individual Rabs into specific subfamilies based on molecular phylogenetics. For genes that were difficult to classify by sequence similarity alone, we did a comparative analysis of intron position among specific subfamilies from yeast to humans. This two-pronged approach allowed the classification of 30 out of 31 C. elegans Rab proteins identified here including Rab31/Rab50, a likely member of the last eukaryotic common ancestor (LECA). Second, a molecular toolset was created to facilitate research on biological processes that involve Rab proteins. Specifically, we used Gateway-compatible C. elegans ORFeome clones as starting material to create 44 full-length, sequence-verified, dominant-negative (DN) and constitutive active (CA) rab open reading frames (ORFs). Development of this toolset provided independent research projects for students enrolled in a research-based molecular techniques course at California State University, East Bay (CSUEB).

Ecohydrodynamics investigates the hydrodynamic constraints on ecosystems across different temporal and spatial scales. Ecohydrodynamics play a pivotal role in the structure and functioning of marine ecosystems, however the lack of integrated complex flow models for deep-water ecosystems beyond the coastal zone prevents further synthesis in these settings. We present a hydrodynamic model for one of Earth's most biologically diverse deep-water ecosystems, cold-water coral reefs. The Mingulay Reef Complex (western Scotland) is an inshore seascape of cold-water coral reefs formed by the scleractinian coral Lophelia pertusa. We applied single-image edge detection and composite front maps using satellite remote sensing, to detect oceanographic fronts and peaks of chlorophyll a values that likely affect food supply to corals and other suspension-feeding fauna. We also present a high resolution 3D ocean model to incorporate salient aspects of the regional and local oceanography. Model validation using in situ current speed, direction and sea elevation data confirmed the model's realistic representation of spatial and temporal aspects of circulation at the reef complex including a tidally driven current regime, eddies, and downwelling phenomena. This novel combination of 3D hydrodynamic modelling and remote sensing in deep-water ecosystems improves our understanding of the temporal and spatial scales of ecological processes occurring in marine systems. The modelled information has been integrated into a 3D GIS, providing a user interface for visualization and interrogation of results that allows wider ecological application of the model and that can provide valuable input for marine biodiversity and conservation applications.