bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of disease among the world’s poorest billion people: An expert-informed secondary analysis of Global Burden of Disease estimates
Authors: Coates Matthew M. , Ezzati Majid , Robles Aguilar Gisela , Kwan Gene F. , Vigo Daniel , Mocumbi Ana O. , Becker Anne E. , Makani Julie , Hyder Adnan A. , Jain Yogesh , Stefan D. Cristina , Gupta Neil , Marx Andrew , Bukhman Gene 
Published: August 2021

Background
The health of populations living in extreme poverty has been a long-standing focus of global development efforts, and continues to be a priority during the Sustainable Development Goal era. However, there has not been a systematic attempt to quantify the magnitude and causes of the burden in this specific population for almost two decades. We estimated disease rates by cause for the world’s poorest billion and compared these rates to those in high-income populations.

Methods
We defined the population in extreme poverty using a multidimensional poverty index. We used national-level disease burden estimates from the 2017 Global Burden of Disease Study and adjusted these to account for within-country variation in rates. To adjust for within-country variation, we looked to the relationship between rates of extreme poverty and disease rates across countries. In our main modeling approach, we used these relationships when there was consistency with expert opinion from a survey we conducted of disease experts regarding the associations between household poverty and the incidence and fatality of conditions. Otherwise, no within-country variation was assumed. We compared results across multiple approaches for estimating the burden in the poorest billion, including aggregating national-level burden from the countries with the highest poverty rates. We examined the composition of the estimated disease burden among the poorest billion and made comparisons with estimates for high-income countries.

Results
The composition of disease burden among the poorest billion, as measured by disability-adjusted life years (DALYs), was 65% communicable, maternal, neonatal, and nutritional (CMNN) diseases, 29% non-communicable diseases (NCDs), and 6% injuries. Age-standardized DALY rates from NCDs were 44% higher in the poorest billion (23,583 DALYs per 100,000) compared to high-income regions (16,344 DALYs per 100,000). Age-standardized DALY rates were 2,147% higher for CMNN conditions (32,334 DALYs per 100,000) and 86% higher for injuries (4,182 DALYs per 100,000) in the poorest billion, compared to high-income regions.

Conclusion
The disease burden among the poorest people globally compared to that in high income countries is highly influenced by demographics as well as large disparities in burden from many conditions. The comparisons show that the largest disparities remain in communicable, maternal, neonatal, and nutritional diseases, though NCDs and injuries are an important part of the “unfinished agenda” of poor health among those living in extreme poverty.
A mixed-methods study to evaluate the effectiveness and cost-effectiveness of aerobic exercise for primary dysmenorrhea: A study protocol
Authors: Kannan Priya , Cheung Kwok-Kuen , Lau Benson Wui-Man , Li Lin , Chen Huijun , Sun Fenghua 
Published: August 2021

Background and purpose
Several studies have evaluated the effects of high-intensity aerobic training (HIAT) on pain severity and quality of life (QoL) among women with primary dysmenorrhea. However, to date, no studies have evaluated the effectiveness of HIAT on academic performance or absenteeism or examined the cost-effectiveness of HIAT relative to other treatments in women with primary dysmenorrhea. Furthermore, the mechanisms underlying aerobic exercise-induced analgesia in primary dysmenorrhea remain unclear. The objectives of this study are to: (1) evaluate the effects of HIAT on absenteeism and academic performance among university students, (2) identify the underlying mechanisms associated with aerobic exercise-induced analgesia in primary dysmenorrhea, and (3) determine the cost-effectiveness of HIAT compared with a wait-list control (WLC) group receiving usual care.

Methods
A sequential, embedded, mixed-methods study design, including a crossover, randomised controlled trial (RCT) and semi-structured focus groups, will be conducted alongside an economic evaluation. A total of 130 women aged 18–24 years will be randomised into either HIAT (n = 65) or wait-list control (n = 65) groups. Primary outcomes will include average pain intensity, absenteeism from university, and academic performance. Primary mediators will include salivary progesterone and prostaglandin F2α levels. Outcome and meditator variables will be assessed at baseline and post-treatment, at 12 and 28 weeks. An economic analysis will be conducted from the societal and healthcare perspective of Hong Kong. Semi-structured focus groups will be conducted at 32 weeks. Of the 130 participants included in the RCT, 70 will be included in the focus groups.

Statistical analysis
All statistical analyses will be performed on an intention-to-treat basis, using SPSS (version 24). Preliminary analysis using an independent samples t-test and a two-sided, unpaired Student’s t-test will be performed to exclude carryover effects and identify within-participant differences in outcome variables between the study periods, respectively. Treatment effects will be evaluated using analysis of variance via a mixed-effects model with fixed effects for intervention, period, and sequence. In all models, random effects will include the participants nested within the sequence as a sampling cluster. The mediation effects will be assessed using the Sobel test. The EQ-5D responses will be converted into utility scores to estimate the gain or loss of quality-adjusted life-years. Seemingly unrelated regression analyses will be used to estimate the total cost differences and effect differences. Qualitative data will be analysed using the process of thematic analysis.
Investigation of population-based mental health staffing and efficiency-based mental health productivity using an information-theoretic approach
Authors: Boden Matt , Smith Clifford A. , Trafton Jodie A. 
Published: August 2021

Background
Healthcare systems monitor and improve mental health treatment quality, access, continuity and satisfaction through use of population-based and efficiency-based staffing models, the former focused on staffing ratios and the latter, staff productivity. Preliminary evidence suggests that both high staffing ratios and moderate-to-high staff productivity are important for ensuring a full continuum of mental health services to indicated populations.

Methods & findings
With an information-theoretic approach, we conducted a longitudinal investigation of mental health staffing, productivity and treatment at the largest integrated healthcare system in American, the Veterans Health Administration (VHA). VHA facilities (N = 140) served as the unit of measure, with mental health treatment quality, access, continuity and satisfaction predicted by facility staffing and productivity in longitudinal mixed models. An information-theoretic approach: (a) entails the development of a comprehensive set of plausible models that are fit, ranked and weighted to quantitatively assess the relative support for each, and (b) accounts for model uncertainty while identifying best-fit model(s) that include important and exclude unimportant explanatory variables. In best-fit models, higher staffing was the strongest and most consistent predictor of better treatment quality, access, continuity and satisfaction. Higher staff productivity was often, but not always associated with better treatment quality, access, continuity and satisfaction. Results were further nuanced by differential prediction of treatment by between- and within-facility predictor effects and variable interactions.

Conclusions
A population-based mental health staffing ratio and an efficiency-based productivity value are important longitudinal predictors of mental health treatment quality, access, continuity and satisfaction. Our longitudinal design and use of mixed regression models and an information-theoretic approach addresses multiple limitations of prior studies and strengthen our results. Results are discussed in terms of the provision of mental health treatment by healthcare systems, and analytical modeling of treatment quality, access, continuity and satisfaction.
Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study
Authors: Liu Jing , Ji Chao-Ran , Li Yue-Yue , Qiao Chen , Hu Jun-Nan , Wan Meng , Lin Min-Juan , Lin Bo-Shen , Wang Juan , Zha Jing , Li Li-Xiang , Zuo Xiu-Li 
Published: August 2021

INTRODUCTION:
We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection.

METHODS:
Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed.

RESULTS:
Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3–7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin).

DISCUSSION:
Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.
Integrating Tumor Sequencing Into Clinical Practice for Patients With Mismatch Repair-Deficient Lynch Syndrome Spectrum Cancers
Authors: Dixon Katherine , Asrat Mary-Jill , Bedard Angela C. , Binnington Kristin , Compton Katie , Cremin Carol , Heidary Nili , Lohn Zoe , Lovick Niki , McCullum Mary , Mindlin Allison , O'Loughlin Melanie , Petersen Tammy , Portigal-Todd Cheryl , Scott Jenna , St-Martin Genevieve , Thompson Jennifer , Turnbull Ruth , Mung Sze Wing , Hong Quan , Bezeau Marjorie , Bosdet Ian , Tucker Tracy , Young Sean , Yip Stephen , Aubertin Gudrun , Blood Katherine A. , Nuk Jennifer , Sun Sophie , Schrader Kasmintan A. 
Published: August 2021

INTRODUCTION:
Uninformative germline genetic testing presents a challenge to clinical management for patients suspected to have Lynch syndrome, a cancer predisposition syndrome caused by germline variants in the mismatch repair (MMR) genes or EPCAM.

METHODS:
Among a consecutive series of MMR-deficient Lynch syndrome spectrum cancers identified through immunohistochemistry-based tumor screening, we investigated the clinical utility of tumor sequencing for the molecular diagnosis and management of suspected Lynch syndrome families. MLH1-deficient colorectal cancers were prescreened for BRAF V600E before referral for genetic counseling. Microsatellite instability, MLH1 promoter hypermethylation, and somatic and germline genetic variants in the MMR genes were assessed according to an established clinical protocol.

RESULTS:
Eighty-four individuals with primarily colorectal (62%) and endometrial (31%) cancers received tumor-normal sequencing as part of routine clinical genetic assessment. Overall, 27% received a molecular diagnosis of Lynch syndrome. Most of the MLH1-deficient tumors were more likely of sporadic origin, mediated by MLH1 promoter hypermethylation in 54% and double somatic genetic alterations in MLH1 (17%). MSH2-deficient, MSH6-deficient, and/or PMS2-deficient tumors could be attributed to pathogenic germline variants in 37% and double somatic events in 28%. Notably, tumor sequencing could explain 49% of cases without causal germline variants, somatic MLH1 promoter hypermethylation, or somatic variants in BRAF.

DISCUSSION:
Our findings support the integration of tumor sequencing into current Lynch syndrome screening programs to improve clinical management for individuals whose germline testing is uninformative.
Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening
Authors: Lu Ming , Wang Le , Zhang Yuhan , Liu Chengcheng , Lu Bin , Du Lingbin , Liao Xianzhen , Dong Dong , Wei Donghua , Gao Yi , Shi Jufang , Ren Jiansong , Chen Hongda , Dai Min 
Published: August 2021

INTRODUCTION:
Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation.

METHODS:
We included 3,407 participants aged 50–74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening.

RESULTS:
Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%–76.3% vs 13.8%–17.3%) but lower specificity (46.6%–90.8% vs 97.4%–98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%–80.9% in AN detection and 82.0%–84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%–14.1% to a decrease of 55.6%–60.1% in AN detection, with the reduction of cost from 4.2%–5.3% rising to 66.4%–68.5%.

DISCUSSION:
With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies.
Colchicine for acute arthritis attacks prevention in patients with gout during urate-lowering therapy (results of a pilot study)
Authors: Eliseev M. S. , Chikina M. N. , Zhelyabina O. V. 
Published: August 2021

Objective: to investigate the efficacy and safety of low-dose colchicine in patients with gout receiving urate-lowering therapy (ULT).Patients and methods. A single-center prospective study included 113 patients with gout. The main group consisted of 92 patients who were prescribed colchicine 0.5 mg/day combined with ULT (allopurinol or febuxostat), control group – 21 patients with contraindications to colchicine therapy who received only ULT. Patient data were entered into individual registration cards at the first visit, as well as on the 90th and 180th day after the start of drug intake. The presence of arthritis attacks was recorded by doctor or patient using a validated questionnaire. We compared the mean frequency of arthritis attacks in the groups, their duration and maximum pain intensity according to the visual analogue scale (VAS). Laboratory tests included: complete blood count test, general urinary test, uric acid (UA), blood glucose, alanine aminotransferase, aspartate aminotransferase, creatinine, serum creatine phosphokinase.Results and discussion. Patients who did not receive prophylactic anti-inflammatory therapy had significantly longer duration of the disease and higher number of affected joints. For 6 months of follow-up, there were no arthritis attacks in 54% of patients who were prescribed colchicine, and only in 19% of patients who did not use prophylactic anti-inflammatory therapy (p=0.004). The duration of arthritis attacks and the intensity of pain according to the VAS were also statistically significantly lower in the colchicine group (p<0.031 and p<0.01, respectively). Due to the development of adverse events, related to colchicine therapy, only 3 were excluded from the study. The mean serum UA level by the end of the study in colchicine group did not differ from that in the control group.Conclusion. Administration of colchicine, 0.5 mg/dai for 6 months after initiation of ULT is safe and can reduce the frequency and severity of arthritis attacks.
Results of a prospective 6-year observational study of the efficacy and safety of a bioactive concentrate of small marine fish in senile patients with knee osteoarthritis and multimorbidity
Authors: Letaeva M. V. , Koroleva M. V. , Raskina T. A. , Malyshenko O. S. , Averkieva Yu. V. , Usova E. V. 
Published: August 2021

Objective: to evaluate the efficacy and safety of Alflutop therapy in elderly patients (75–90 years old) with knee osteoarthritis (OA) and multimorbidity based on the results of a prospective 6-year follow-up.Patients and methods. The study included 38 elderly women with knee OA (according to ACR criteria, 1986) stage II–III by Kellgren–Lawrence grading system, with pain ≥40 mm by visual analogue scale (VAS), who needed to take non-steroidal anti-inflammatory drugs (NSAIDs). Alflutop was administered as 1 ml intramuscular injections 20 consecutive days with a 6-month interval (12 courses). The effectiveness of therapy was assessed by VAS, WOMAC index and EQ-5D questionnaire. The safety of therapy was monitored throughout the observation period. The duration of the study was 6 years.Results and discussion. The full course of treatment with Alflutop was completed by 29 (76.3%) patients. Nine (23.7%) patients discontinued the study due to their inability to visit the treatment center (for reasons unrelated to the study).In elderly patients with knee OA, high level of multimorbidity was revealed, 5 comorbidities on average.There was a significant decrease in pain according to VAS (≥20%): by visit (V) 1 – in 76.3%, by V2 – in 71.0%, by V3 – in 68.4%, by V4 – in 63.1% and by V5 – in 55.2% of patients. By the 21st day of Alflutop therapy, a statistically significant decrease in the total WOMAC index (p<0.001) and an improvement in the quality of life according to the EQ-5D questionnaire (p=0.016) were found. These indicators remained relatively stable throughout the follow-up. By the 12th month, a decrease of the need of NSAIDs was registered (p=0.005).X-ray progression of OA stage ≥1 according to Kellgren–Lawrence on Alflutop therapy after 36 months of observation was recorded in 10.5% of patients, after 72 months – in 50.0%. No serious adverse events were registered during entire observation period.Conclusion. The results of a 6-year prospective study demonstrate the high efficacy of Alflutop in elderly patients with knee OA. The obtained data confirm the safety of long-term treatment with this drug in elderly patients with high multimorbidity, which makes it the first-line drug in the complex therapy of OA.
Menstrual cycle and gynecologic pathology in menstrual-related migraine
Authors: Kiryanova E. A. , Tabeeva G. R. 
Published: August 2021

Migraine is the first most frequent cause of disability among women of reproductive age globally, and up to 60% of patients note the association of headache attacks with menstruation.Objective: to determine the features of menstrual cycle and gynecologic pathology in women with menstrual-related migraine (MRM).Patients and methods. A prospective comparative study included 69 women of reproductive age with a migraine diagnosis who did not receive hormonal contraception. Depending on the association of migraine attacks with menstruation (according to headache diaries), the patients were divided into two groups: the 1st group consisted of 44 patients with MRM; group 2 — 25 patients with non-menstrual migraine (without the association of attacks with menstruation).Results and discussion. Patients with MRM had heavier menstrual bleeding, longer menstruations (more than six days), abnormal menstrual cycle length and regularity, dysmenorrhea. In addition, the obtained data indicate a comorbid estrogen-associated gynecological pathology (endometriosis, adenomyosis, endometrial polyps, myoma) in MRM.Conclusion. Presumably, the hypothalamic-pituitary-ovarian axis dysfunction plays the leading role in the MRM. It presents with menstrual cycle abnormalities and increased presence of estrogen-associated gynecological pathology, which should be considered during patient evaluation and suggesting recommendations.
Methionine synthase reductase A66G polymorphism and ischemic stroke in younger patients
Authors: Tsyganenko O. V. , Volkova L. I. , Alasheev A. M. 
Published: August 2021

In the past decade, stroke incidence in younger adults increased. Methionine synthase reductase (MTRR) A66G polymorphism is one of the risk factors for ischemic stroke (IS). However, clinical features of IS in MTRR A66G polymorphism are not yet studied.Objective: to investigate clinical features of IS in MTRR A66G polymorphism.Patients and methods. One hundred forty-one younger patients with IS, hospitalized in the neurological department of Sverdlovsk Regional Clinical Hospital №1, were included in the study. MTRR A66G polymorphism was detected by the real-time polymerase chain reaction in all participants.Results and discussion. MTRR A66G polymorphism was present in 83.7% of younger patients with IS. Participants with MTRR A66G polymorphism had a significantly higher prevalence of arterial hypertension (р=0.029). In addition, protein C level was significantly lower in patients with MTRR A66G mutation (р=0.001).Conclusion. The majority of younger patients with IS have MTRR A66G polymorphism. Therefore, the inclusion of MTRR A66G polymorphism screening in the diagnostic algorithm of stroke in young adults seems necessary.