bluuebunny/crossref_metadata_2025_split huggingface dataset:
The global burden of chromoblastomycosis
Authors: Santos Daniel Wagner C. L. , de Azevedo Conceição de Maria Pedrozo e Silva , Vicente Vania Aparecida , Queiroz-Telles Flávio , Rodrigues Anderson Messias , de Hoog G. Sybren , Denning David W. , Colombo Arnaldo Lopes 
Published: August 2021

Background
Chromoblastomycosis (CBM), represents one of the primary implantation mycoses caused by melanized fungi widely found in nature. It is characterized as a Neglected Tropical Disease (NTD) and mainly affects populations living in poverty with significant morbidity, including stigma and discrimination.

Methods and findings
In order to estimate the global burden of CBM, we retrospectively reviewed the published literature from 1914 to 2020. Over the 106-year period, a total of 7,740 patients with CBM were identified on all continents except Antarctica. Most of the cases were reported from South America (2,619 cases), followed by Africa (1,875 cases), Central America and Mexico (1,628 cases), Asia (1,390 cases), Oceania (168 cases), Europe (35 cases), and USA and Canada (25 cases). We described 4,022 (81.7%) male and 896 (18.3%) female patients, with the median age of 52.5 years. The average time between the onset of the first lesion and CBM diagnosis was 9.2 years (range between 1 month to 50 years). The main sites involved were the lower limbs (56.7%), followed by the upper limbs (19.9%), head and neck (2.9%), and trunk (2.4%). Itching and pain were reported by 21.5% and 11%, respectively. Malignant transformation was described in 22 cases. A total of 3,817 fungal isolates were cultured, being 3,089 (80.9%) Fonsecaea spp., 552 (14.5%) Cladophialophora spp., and 56 Phialophora spp. (1.5%).

Conclusions and significance
This review represents our current knowledge on the burden of CBM world-wide. The global incidence remains unclear and local epidemiological studies are required to improve these data, especially in Africa, Asia, and Latin America. The recognition of CBM as NTD emphasizes the need for public health efforts to promote support for all local governments interested in developing specific policies and actions for preventing, diagnosing and assisting patients.
Individual and community factors determining delayed leprosy case detection: A systematic review
Authors: Dharmawan Yudhy , Fuady Ahmad , Korfage Ida , Richardus Jan Hendrik 
Published: August 2021

Background
The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection.

Methods
This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library.

Results
We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor.

Conclusions
Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay.
The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study
Authors: Milic Jovana , Banchelli Federico , Meschiari Marianna , Franceschini Erica , Ciusa Giacomo , Gozzi Licia , Volpi Sara , Faltoni Matteo , Franceschi Giacomo , Iadisernia Vittorio , Yaacoub Dina , Dolci Giovanni , Bacca Erica , Rogati Carlotta , Tutone Marco , Burastero Giulia , Raimondi Alessandro , Menozzi Marianna , Cuomo Gianluca , Corradi Luca , Orlando Gabriella , Santoro Antonella , Digaetano Margherita , Puzzolante Cinzia , Carli Federica , Bedini Andrea , Busani Stefano , Girardis Massimo , Cossarizza Andrea , Miglio Rossella , Mussini Cristina , Guaraldi Giovanni , D’Amico Roberto 
Published: August 2021

Background
The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery.

Methods
In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery.

Results
Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab.

Conclusion
To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.
Factors hindering integration of care for non-communicable diseases within HIV care services in Dar es Salaam, Tanzania: The perspectives of health workers and people living with HIV
Authors: Haruna Tausi , Somba Magreat , Siril Hellen , Mahiti Gladys , August Francis , Minja Anna , Urassa David , Tarimo Edith , Mugusi Ferdinand 
Published: August 2021

BackgroundGlobal mortality attributable to non-communicable diseases (NCDs) occurs in more than 36 million people annually with 80% of these deaths occurring in resource limited countries. Among people living with HIV and AIDS (PLHA) studies have reported higher prevalence’s of NCDs compared to the general population but most studies do report a narrow range of NCDs commonly hypertension, diabetes and neoplasms and not all. In addition, there is limited reporting, integration of systematic screening and treatment for all NCDs among PLHA attending care, suggesting the NCD burden among PLHA is likely an underestimate. Little is known about factors facilitating or hindering integration of the care and treatment of NCDs within HIV care and treatment clinics (CTCs) in Tanzania.ObjectiveTo explore the perceptions of PLHA and health workers on factors facilitate or hinder the recognition and integration of care for NCDs within CTCs in Dar es Salaam.MethodsInductive content analysis of transcripts from 41 in-depth interviews were conducted with 5 CTC managers (CTC Managers), 9 healthcare providers (DHCP) and 27 people living with HIV (PLHA) attending CTCs and with co-morbid NCDs.ResultsFour themes emerged; the current situation of services available for care and treatment of NCDs among PLHA in CTCs, experiences of PLHA with co-morbid NCDs with access to care and treatment services for NCDs, facilitators of integrating care and treatment of NCDs within CTCs and perceived barriers for accessing and integration of care and treatment of NCDs within CTCs.ConclusionsThere was a positive attitude among PLHA and healthcare workers towards integration of NCD services within CTC services. This was enhanced by perceived benefits inherent to the services. Factors hindering integration of NCD care and services included; limited and inconsistent supplies such as screening equipment, medications; insufficient awareness of NCDs within PLHA; lack of adequate training of healthcare workers on management of NCD and treatment costs and payment systems.
Preliminary model assessing the cost-effectiveness of preoperative chlorhexidine mouthwash at reducing postoperative pneumonia among abdominal surgery patients in South Africa
Authors: Kachapila Mwayi , Ademuyiwa Adesoji O. , Biccard Bruce M. , Ghosh Dhruva N. , Glasbey James , Monahan Mark , Moore Rachel , Morton Dion G. , Oppong Raymond , Pearse Rupert , Roberts Tracy E. ,   NIHR Global Health Research Unit on Global Surgery,   ASOS Investigators,   STARSurg Collaborative
Published: August 2021

Background
Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients.

Methods
A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves.

Results
In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery, $3,675 (R 63,770) versus $3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between $0 (R0) and $15,000 (R 260,220) willingness to pay thresholds.

Conclusions
Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.
Impact of the DREAMS interventions on educational attainment among adolescent girls and young women: Causal analysis of a prospective cohort in urban Kenya
Authors: Mulwa Sarah , Chimoyi Lucy , Agbla Schadrac , Osindo Jane , Wambiya Elvis O. , Gourlay Annabelle , Birdthistle Isolde , Ziraba Abdhalah , Floyd Sian 
Published: August 2021

Background
DREAMS promotes a comprehensive HIV prevention approach to reduce HIV incidence among adolescent girls and young women (AGYW). One pathway that DREAMS seeks to impact is to support AGYW to stay in school and achieve secondary education. We assessed the impact of DREAMS on educational outcomes among AGYW in Nairobi, Kenya.

Methods and findings
In two informal settlements in Nairobi, 1081 AGYW aged 15−22 years were randomly selected in 2017 and followed-up to 2019. AGYW reporting invitation to participate in DREAMS during 2017–18 were classified as “DREAMS beneficiaries”. Our main outcome was being in school and/or completed lower secondary school in 2019. We used multivariable logistic regression to quantify the association between being a DREAMS beneficiary and the outcome; and a causal inference framework to estimate proportions achieving the outcome if all, versus no, AGYW were DREAMS beneficiaries, adjusting for the propensity to be a DREAMS beneficiary. Of AGYW enrolled in 2017, 79% (852/1081) were followed-up to 2019. In unadjusted analysis, DREAMS beneficiaries had higher attainment than non-beneficiaries (85% vs 75% in school or completed lower secondary school, Odds Ratio (OR) = 1.9; 95%CI: 1.3,2.8). The effect weakened with adjustment for age and other confounders, (adjusted OR = 1.4; 95%CI: 0.9,2.4). From the causal analysis, evidence was weak for an impact of DREAMS (estimated 83% vs 79% in school or completed lower secondary school, if all vs no AGYW were beneficiaries, difference = 4%; 95%CI: -2,11%). Among AGYW out of school at baseline, the estimated differences were 21% (95%CI: -3,43%) among 15−17 year olds; and 4% (95%CI: -8,17%) among 18−22 year olds.

Conclusions
DREAMS had a modest impact on educational attainment among AGYW in informal settlements in Kenya, by supporting both retention and re-enrolment in school. Larger impact might be achieved if more AGYW were reached with educational subsidies, alongside other DREAMS interventions.
Association of fibroblast growth factor 10 with the fibrotic and inflammatory pathogenesis of Graves’ orbitopathy
Authors: Jang Sun Young , Choi Soo Hyun , Kikkawa Don , Lee Eun Jig , Yoon Jin Sook 
Published: August 2021

Purpose
The role of fibroblast growth factor (FGF) in orbital fibroblasts (OFs) is rarely known. In this study, we investigated the effect of FGF10 on fibrosis and the inflammation mechanism of Graves′ orbitopathy (GO).

Methods
Orbital tissue from GO (n = 15) and non-GO (n = 15) was obtained for this study. The mRNA and protein expression levels of FGF10 and FGF receptor 2b (FGFR2b) in orbital tissue were determined by real-time polymerase chain reaction, western blot analysis, and confocal microscopy. The effects of FGF10 on transforming growth factor (TGF)-β1 induced fibrotic proteins and interleukin (IL)-1β- or tumor necrosis factor (TNF)-α- induced inflammatory proteins were investigated using recombinant human (rh) FGF10 and small interfering (si) RNA transfection against FGF10.

Results
FGF10 and FGFR2b mRNA expression levels were significantly lower in GO orbital tissues than in non-GO orbital tissues (p = 0.009 and 0.005, respectively). Immunostaining of FGF10 in orbital adipose tissues showed differences in FGF10 expression between GO and control samples. Immunostaining of FGF10 was very weak in the orbital tissues of GO patients. TGF-β1-induced fibronectin, collagen Iα, α-smooth muscle actin protein expression in GO OFs was attenuated by rhFGF10 treatment and increased by knockdown of FGF10 via siFGF10 transfection. Similarly, IL-1β- or TNF-α-induced IL-6, IL-8, and cyclooxygenase-2 protein production in GO OFs was either blocked by rhFGF10 treatment or further upregulated by inhibition of FGF10 via siFGF10 transfection.

Conclusions
Our data demonstrate that FGF10 has beneficial effects on the inflammatory and fibrotic mechanisms of GO in primary cultured OFs, providing new insights into GO pathology and the discovery of FGF10 as a promising novel therapeutic application for the treatment of GO.
What are the biopsychosocial risk factors associated with pain in postpartum runners? Development of a clinical decision tool
Authors: Christopher Shefali Mathur , Cook Chad E. , Snodgrass Suzanne J. 
Published: August 2021

BackgroundIn 2019, a majority of runners participating in running events were female and 49% were of childbearing age. Studies have reported that women are initiating or returning to running after childbirth with up to 35% reporting pain. There are no studies exploring running-related pain or risk factors for this pain after childbirth in runners. Postpartum runners have a variety of biomechanical, musculoskeletal, and physiologic impairments from which to recover from when returning to high impact sports like running, which could influence initiating or returning to running. Therefore, the purpose of this study was to identify risk factors associated with running-related pain in postpartum runners with and without pain. This study also aimed to understand the compounding effects of multiple associative risk factors by developing a clinical decision tool to identify postpartum runners at higher risk for pain.MethodsPostpartum runners with at least one child ≤36 months who ran once a week and postpartum runners unable to run because of pain, but identified as runners, were surveyed. Running variables (mileage, time to first postpartum run), postpartum variables (delivery type, breastfeeding, incontinence, sleep, fatigue, depression), and demographic information were collected. Risk factors for running-related pain were analyzed in bivariate regression models. Variables meeting criteria (P<0.15) were entered into a multivariate logistic regression model to create a clinical decision tool. The tool identified compounding factors that increased the probability of having running-related pain after childbirth.ResultsAnalyses included 538 postpartum runners; 176 (32.7%) reporting running-related pain. Eleven variables were included in the multivariate model with six retained in the clinical decision tool: runner type-novice (OR 3.51; 95% CI 1.65, 7.48), postpartum accumulated fatigue score of >19 (OR 2.48; 95% CI 1.44, 4.28), previous running injury (OR 1.95; 95% CI 1.31, 2.91), vaginal delivery (OR 1.63; 95% CI 1.06, 2.50), incontinence (OR 1.95; 95% CI 1.31, 2.84) and <6.8 hours of sleep on average per night (OR 1.89; 95% CI 1.28, 2.78). Having ≥ 4 risk factors increased the probability of having running-related pain to 61.2%.ConclusionThe results of this study provide a deeper understanding of the risk factors for running-related pain in postpartum runners. With this information, clinicians can monitor and educate postpartum runners initiating or returning to running. Education could include details of risk factors, combinations of factors for pain and strategies to mitigate risks. Coaches can adapt running workload accounting for fatigue and sleep fluctuations to optimize recovery and performance. Future longitudinal studies that follow asymptomatic postpartum women returning to running after childbirth over time should be performed to validate these findings.
The interobserver agreement of ECG abnormalities using Minnesota codes in people with type 2 diabetes
Authors: Nijpels Giel , van der Heijden Amber A. W. A. , Elders Petra , Beulens Joline W. J. , de Vet Henrica C. W. 
Published: August 2021

Objectives
To assess the interobserver agreement in categories of electrocardiogram (ECG) abnormalities using the Minnesota Code criteria.

Methods
We used a random sample of 180 ECGs from people with type 2 diabetes. ECG abnormalities were classified and coded using the Minnesota ECG Classification. Each ECG was independently rated on several abnormalities by an experienced rater (rater 1) and by two cardiologists (raters 2 and 3) trained to apply the Minnesota codes on four Minnesota codes; 1-codes as an indication for myocardial infarction, 4 en 5-codes as an indication for ischemic abnormalities, 3-codes as an indication for left ventricle hypertrophy, 7-1-codes as an indication for ventricular conduction abnormalities, and 8-3-codes as an indication for atrial fibrillation / atrial flutter. After all pairwise tables were summed, the overall agreement, the specific positive and negative agreement were calculated with a 95% confidence interval (CI) for each abnormality. Also, Kappa’s with a 95% CI were calculated.

Results
The overall agreement (with 95% CI) were for myocardial infarction, ischemic abnormalities, left ventricle hypertrophy, conduction abnormalities and atrial fibrillation/atrial flutter respectively: 0.87 (0.84–0.91), 0.79 (0.74–0.84), 0.81 (0.76–0.85), 0.93 (0.90–0.95), 0.96 (0.93–0.97).

Conclusion
This study shows that the overall agreement of the Minnesota code is good to excellent.
Evaluation of availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria
Authors: Osuafor Nkeiruka Grace , Ukwe Chinwe Victoria , Okonta Mathew 
Published: August 2021

Objective
To assess the availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria.

Methods
A cross-sectional survey involving 27 private pharmacies, 13 public pharmacies, and 25 private hospital pharmacies in Abuja was conducted using the standardized World Health Organization/Health Action International methodology. The availability percentage for each pharmacy sector and each medicine was analyzed. The median price ratio (MPR) (ratio of the median price to the international reference prices) of the medicines were evaluated accordingly. Affordability was assessed by calculating the number of days’ wages the lowest-paid unskilled government worker required to purchase a month worth of the standard treatment for a chronic condition.

Results
The availability of cardiovascular (CV) medicines ranged from 28.4% (in private hospital pharmacies) to 59.9% (in private pharmacies). There was mixed variability in the mean availability of Originator Brands (OBs) and Lowest Priced Generics (LPGs) anti-diabetic drugs with the highest availability being OBs 36% and LPGs 40.2%, in private pharmacies and public pharmacies, respectively. The availability of global drugs ranged from 49.7% in private hospitals to 68.8% in private pharmacies. Two cardiovascular and four global medicines had greater than 80% availability across the pharmaceutical sectors. The median price ratio for OBs and LPGs was 9.60 and 1.72 for procurement, it was 8.08 and 2.60 in private pharmacies, 13.56 and 2.66 in public hospitals, and 16.38 and 7.89 in private hospitals. The percentage markup on LPG was 49.4% in public hospitals, 51.4% in private pharmacies, and 323% in private hospitals. Only nine medicines in both public hospitals and private pharmacies and two in the private hospital pharmacies required less than the daily wage of the lowest-paid government worker.

Conclusion
The availability of cardiovascular, diabetes, and global medicines was below 80% across the different pharmaceutical sectors in Abuja and the medicines were unaffordable. Although the prices were generally exorbitant, private pharmacies offered the best options in terms of availability, pricing, and affordability of medicines. Therefore, the results of this study emphasize the pertinence of enforcing policies that facilitate the availability, pricing, and affordability of cardiovascular, diabetes, and global medicines.