bluuebunny/crossref_metadata_2025 huggingface dataset:
Common genetic variants do not predict recurrent events in coronary heart disease patients
Authors: Thompson P. L. , Hui J. , Beilby J. , Palmer L. J. , Watts G. F. , West M. J. , Kirby A. , Marschner S. , Simes R. J. , Sullivan D. R. , White H. D. , Stewart R. , Tonkin A. M.
Published: March 2022

Background

It is unclear whether genetic variants identified from single nucleotide polymorphisms (SNPs) strongly associated with coronary heart disease (CHD) in genome-wide association studies (GWAS), or a genetic risk score (GRS) derived from them, can help stratify risk of recurrent events in patients with CHD.

Methods

Study subjects were enrolled at the close-out of the LIPID randomised controlled trial of pravastatin vs placebo. Entry to the trial had required a history of acute coronary syndrome 3–36 months previously, and patients were in the trial for a mean of 36 months. Patients who consented to a blood sample were genotyped with a custom designed array chip with SNPs chosen from known CHD-associated loci identified in previous GWAS. We evaluated outcomes in these patients over the following 10 years.

Results

Over the 10-year follow-up of the cohort of 4932 patients, 1558 deaths, 898 cardiovascular deaths, 727 CHD deaths and 375 cancer deaths occurred. There were no significant associations between individual SNPs and outcomes before or after adjustment for confounding variables and for multiple testing. A previously validated 27 SNP GRS derived from SNPs with the strongest associations with CHD also did not show any independent association with recurrent major cardiovascular events.

Conclusions

Genetic variants based on individual single nucleotide polymorphisms strongly associated with coronary heart disease in genome wide association studies or an abbreviated genetic risk score derived from them did not help risk profiling in this well-characterised cohort with 10-year follow-up. Other approaches will be needed to incorporate genetic profiling into clinically relevant stratification of long-term risk of recurrent events in CHD patients.
EZH2 mitigates the cardioprotective effects of mesenchymal stem cell-secreted exosomes against infarction via HMGA2-mediated PI3K/AKT signaling
Authors: Jiao Wei , Hao Jie , Xie Yanan , Meng Mingjie , Gao Weinian
Published: March 2022

Background

Mesenchymal stem cell-derived exosomes (MSC-EXO) have emerged as novel therapeutic strategies for myocardial infarction (MI). However, many questions remain untouched and unanswered regarding their roles in myocardial fibrosis. This study aimed to probe the therapeutic effects of MSC-EXO on myocardial fibrosis after MI and possible mechanisms.

Methods

Myocardial tissues were obtained from MI rats, and myocardial cell viability, fibrosis, apoptosis, and epithelial–mesenchymal transition (EMT) were detected by immunohistochemistry, Masson’s staining, TUNEL, and western blot. Bone marrow-derived MSCs and corresponding EXO were identified, and cardiac function were detected after treatment of MSC-EXO. Bioinformatics analysis and ChIP assay were conducted to detect the downstream genes of EZH2. EZH2 was upregulated alone or with HMGA2 overexpression in myocardial tissues of MI rats upon MSC-EXO treatment, and PI3K/AKT pathway activity in myocardial tissues was detected using western blot.

Results

The proliferative activity in myocardial tissues of MI rats was significantly decreased, along with accentuated fibrosis, increased collagen volume and EMT. MSC-EXO treatment resulted in partial restoration of cardiac function and reduced EZH2 expression in the myocardium of rats. EZH2 inhibited HMGA2 expression by increasing the H3K27me3 modification. PI3K/AKT pathway was altered under the influence of the EZH2/HMGA2 axis. EZH2 inhibited the effect of MSC-EXO on the recovery of cardiac function and accelerated fibrosis, while HMGA2 reversed the effect of EZH2 to reduce fibrosis and enhance cardiac function.

Conclusion

MSC-EXO alleviated fibrosis in MI rats via inhibition of EZH2, whereas EZH2 inhibited HMGA2 expression and impaired the PI3K/AKT pathway.
The prevalence of antibiotic-resistant and multidrug-resistant bacteria in urine cultures from inpatients with spinal cord injuries and disorders: an 8-year, single-center study
Authors: Šámal Vladimír , Paldus Vít , Fáčková Daniela , Mečl Jan , Šrám Jaroslav
Published: March 2022

Background

Patients, especially inpatients, with spinal cord lesions and disorders (SCI/D) have an elevated risk of recurrent urinary tract infections with multidrug resistant (MDR) bacteria. This study evaluated antimicrobial resistance and the prevalence of multidrug resistance and determined the risk factors for multidrug resistance.

Methods

In this retrospective cohort study, urine culture results were used to calculate the antimicrobial resistance rate and the incidence of infection with MDR bacteria in the SCI/D population. MDR was defined as acquired nonsusceptibility to at least one agent from three or more antimicrobial categories. The cohort included 402 inpatients from 2013 to 2020, with 1385 urine isolates. We included only the first isolate; duplicate isolates, defined as positive cultures of the same strain within 14 days, were excluded from the evaluation.

Results

The most common MDR strains wereKlebsiellaspp.(29%) andEscherichia coli(24%). MDR isolates were detected in 50% of the samples and extended spectrum beta-lactamase (ESBL)-producing isolates were detected in 26%, while carbapenem resistance was found in 0.1%. Significantly higher rates of infection with MDR bacteria were identified in groups of patients with indwelling urethral/suprapubic catheters (p = 0.003) and severity scores of C1–C4/AIS A–C (p = 0.01). We identified age (OR: 0.99, 95% CI; 0.98–0.99, p = 0.000), sex (OR: 1.55, 95% CI; 1.16–2.06, p = 0.003), management with urethral/suprapubic catheters (OR: 2.76, 95% CI; 2.04–3.74, p = 0.000), and spontaneous voiding (OR: 1.84, 95% CI; 1.03–3.29, p = 0.038) as independent predictors of multidrug resistance in our study population.

Conclusions

We identified a high antibiotic resistance rate and an increasing prevalence of infection with MDR bacteria in the SCI/D inpatient population. Particular attention should be given to bladder management, with an emphasis on minimizing the use of indwelling catheters.
Impaired functional network properties contribute to white matter hyperintensity related cognitive decline in patients with cerebral small vessel disease
Authors: Wang Yifan , Liu Xiao , Hu Ying , Yu Zekuan , Wu Tianhao , Wang Junjie , Liu Jie , Liu Jun
Published: March 2022

Background

White matter hyperintensity (WMH) is one of the typical neuroimaging manifestations of cerebral small vessel disease (CSVD), and the WMH correlates closely to cognitive impairment (CI). CSVD patients with WMH own altered topological properties of brain functional network, which is a possible mechanism that leads to CI. This study aims to identify differences in the characteristics of some brain functional network among patients with different grades of WMH and estimates the correlations between these different brain functional network characteristics and cognitive assessment scores.

Methods

110 CSVD patients underwent 3.0 T Magnetic resonance imaging scans and neuropsychological cognitive assessments. WMH of each participant was graded on the basis of Fazekas grade scale and was divided into two groups: (A) WMH score of 1–2 points (n = 64), (B) WMH score of 3–6 points (n = 46). Topological indexes of brain functional network were analyzed using graph-theoretical method. T-test and Mann–Whitney U test was used to compare the differences in topological properties of brain functional network between groups. Partial correlation analysis was applied to explore the relationship between different topological properties of brain functional networks and overall cognitive function.

Results

Patients with high WMH scores exhibited decreased clustering coefficient values, global and local network efficiency along with increased shortest path length on whole brain level as well as decreased nodal efficiency in some brain regions on nodal level (p < 0.05). Nodal efficiency in the left lingual gyrus was significantly positively correlated with patients' total Montreal Cognitive Assessment (MoCA) scores (p < 0.05). No significant difference was found between two groups on the aspect of total MoCA and Mini-mental State Examination (MMSE) scores (p > 0.05).

Conclusion

Therefore, we come to conclusions that patients with high WMH scores showed less optimized small-world networks compared to patients with low WMH scores. Global and local network efficiency on the whole-brain level, as well as nodal efficiency in certain brain regions on the nodal level, can be viewed as markers to reflect the course of WMH.
The congruency of neuropsychological and F18-FDG brain PET/CT diagnostics of Alzheimer’s Disease (AD) in routine clinical practice: insights from a mixed neurological patient cohort
Authors: Hansen Sascha , Keune Jana , Küfner Kim , Meister Regina , Habich Juliane , Koska Julia , Förster Stefan , Oschmann Patrick , Keune Philipp M.
Published: March 2022

Background

Diagnostics of Alzheimer’s Disease (AD) require a multimodal approach. Neuropsychologists examine the degree and etiology of dementia syndromes and results are combined with those of cerebrospinal fluid markers and imaging data. In the diagnostic process, neuropsychologists often rely on anamnestic and clinical information, as well as cognitive tests, prior to the availability of exhaustive etiological information. The congruency of this phenomenological approach with results from FDG-PET/CT examinations remains to be explored. The latter yield highly accurate diagnostic information.

Method

A mixed sample of N = 127 hospitalized neurological patients suspected of displaying a dementia syndrome underwent extensive neuropsychological and FDG-PET/CT examinations. Neuropsychological examinations included an anamnestic and clinical interview, and the CERAD cognitive test battery. Two decisional approaches were considered: First, routine diagnostic results were obtained, i.e. the final clinical decision of the examining neuropsychologist (ADClinical vs. non-ADClinical). Secondly, a logistic regression model was implemented, relying on CERAD profiles alone. CERAD subscales that best predicted AD based on FDG-PET/CT were identified and a nominal categorization obtained (ADTest vs. non-ADTest). Congruency of results from both approaches with those of the FDG-PET/CT (ADPET vs. non-ADPET) were estimated with Cohen’s Kappa (κ) and Yule’s Y coefficient of colligation. Descriptive estimates of accuracy, sensitivity and specificity of CERAD relative to FDG-PET/CT diagnostics were derived.

Results

ADPET patients constituted N = 33/127 (26%) of the sample. The clinical decision approach (ADClinical vs. non-ADClinical) showed substantial agreement with the FDG-PET/CT classification (κ = .69, Y = .72) involving good accuracy (84.2%), moderate sensitivity (75.8%) and excellent specificity (92.6%). In contrast, the decisional approach that relied on CERAD data alone (ADTest vs. non-ADTest) involved only moderate agreement with the FDG-PET/CT (κ = .54, Y = .62) with lower accuracy (74.8%), attributable to decreased sensitivity (56.3%) and comparable specificity (93.3%).

Conclusions

It is feasible to identify AD through a comprehensive neuropsychological examination in a mixed sample of neurological patients. However, within the boundaries of methods applied here, decisions based on cognitive test results alone appear limited. One may conclude that the clinical impression based on anamnestic and clinical information obtained by the neuropsychological examiner plays a crucial role in the identification of AD patients in routine clinical practice.
Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa
Authors: Nyemba Dorothy C. , Peters Remco P. H. , Medina-Marino Andrew , Klausner Jeffrey D. , Ngwepe Phuti , Myer Landon , Johnson Leigh F. , Joseph Davey Dvora L.
Published: March 2022

Background

Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes.

Methods

We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics.

Results

Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV.

Conclusion

Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.
Epidemiology and prognosis factors in open globe injuries in the Federal District of Brazil
Authors: Peleja Marina Berquó , da Cunha Felipe Bruno Santos , Peleja Mariana Berquó , Rohr Juliana Tessari Dias
Published: March 2022

Objective

To identify the epidemiological profile and prognostic factors of open globe injuries that require emergency surgical treatment.

Design

Retrospective cohort study.

Subjects

Patients with OGI who underwent publicly funded emergency surgical treatment in the Federal District from 2014 to 2018.

Methods

Data were collected by reviewing electronic medical records through a questionnaire and tabulated. The statistical analysis was performed in SPSS Statistics 26.0.0.0 (p ≤ 0.05).

Results

A total of 359 records were included, corresponding to 336 eyes of 334 patients (294 males and 40 females). The average age was 32.7 years. The affected eye was the right eye in 165 cases, the left eye in 166 cases, and both eyes in 3 cases. The average time between injury and hospitalization was 75.7 h, and the time between injury and surgery averaged 173.7 h. The injury types were as follows: 197 penetrating; 109 rupture; 19 IOFB; 11 perforating. The injuries were in the following zones: 181 zone I; 82 zone II; 70 zone III. The OTS grades were as follows: 57 were classified as grade 1; 101 were grade 2; 142 were grade 3; 28 were grade 4; and 8 were 5. The most commonly performed surgeries were corneal suture, corneoscleral suture, and evisceration. The most common clinical features were traumatic cataract, herniated iris and hyphema. The following were risk factors for poor prognosis: zone III, time between trauma and surgery > 72 h, rupture injury, retinal detachment, disorganization of the eyeball, endophthalmitis, uveal prolapse, OTS classification 1 or 2, and low initial visual acuity. The following factors predicted a good prognosis: initial VA > 1/200, penetrating injury, OTS 4 and zone II.

Conclusions

The high frequency of many of these factors may explain the high rate of severe visual loss found. Injury localization in zone II was identified as a previously unrecognized protective factor against severe visual loss.
A qualitative exploration of attitudes to walking in the retirement life change
Authors: Searle Aidan , Herbert Georgia , Ness Andy , Foster Charlie , Waylen Andrea , Jago Russell
Published: March 2022

Background

Walking is a simple activity that could help to reduce the prevalence of chronic diseases in all populations. Furthermore, an inverse dose–response relationship exists between steps taken and risk of premature death and cardiovascular events in middle-aged and older adults. There is a lack of information on how to effectively engage older adults around retirement age in walking. This qualitative study explored attitudes towards walking in older people with regard to habits, intensity, preferences and strategies for increasing walking behaviour.

Methods

In-depth qualitative interviews were conducted with 26 older adults who were either close to retirement or recently retired. An inductive thematic analysis was conducted.

Results

Three themes were identified from the data; 1) Engagement and perceived value of walking; was focused on the meaning of walking for the participant and the attributes they associate with their walking practice. 2) Integration and connectivity of walking; was focused on how participants integrate walking in their daily lives and whether walking can be practiced as a viable means of connectivity. 3) Strategies to increase walking; was focused on what factors motivate participants in their walking practice and what strategies they perceived to be beneficial to increase walking distance and intensity at an individual level.

Discussion

The views of walking in people of retirement age were represented within 3 key themes. The factors contained in these themes that may influence future walking practice are discussed with regard to future strategies to promote walking in the retirement life change.

Conclusion

It may be beneficial to promote qualitative aspects of walking practice and strive for regularity rather than intensity of walking to accrue the social, psychological and intellectual benefits reported by individuals in the retirement life change.
Characteristics, expectations, experiences of care, and satisfaction of patients receiving chiropractic care in a French University Hospital in Toulouse (France) over one year: a case study
Authors: F Mallard , N Lemeunier , S Mior , V Pecourneau , P Côté
Published: March 2022

Background

In October 2017, a partnership was established between the University Hospital of Toulouse and the French Chiropractic College, “Institut Franco-Européen de Chiropraxie” (IFEC). Before 2017, chiropractors did not practice in hospitals in France. Chiropractic students and chiropractors are now integrated in an interdisciplinary medical team at University Hospital.

Our study aimed to describe the characteristics of patients who received chiropractic care at the University Hospital of Toulouse, their expectations, experiences of care, and satisfaction.

Method

A prospective case study was conducted. Patients referred for chiropractic care in the French University Hospital of Toulouse from January to December 2020 were eligible to participate. Participants provided the following data: demographics, previous chiropractic care treatments, pain location, intensity (NRS) and duration, disability (NDI, ODI), health-related quality of life (SF-12) and depressive symptomatology (PHQ-9). We conducted semi-structured interviews to explore their expectations, barriers and facilitators impacting their experience of care, and satisfaction.

Results

Seventeen participants were recruited and seven were interviewed. All participants had chronic pain with a median pain intensity of 05/10 (IQR 04–06) on the NRS scale. Nine of 17 participants presented with multiple pain locations. Thirteen of seventeen participants presented with low back pain and eight with neck pain. The median SF-12 health-related quality of life score was 50/100 (IQR 28.5–60.5) for physical health, and 52/100 (IQR 43–62) for mental health. The PHQ-9 median score of depressive symptomatology was 7.7/27 (IQR 2.0–12.5).

Overall, participants were satisfied with their care and the collaboration between chiropractors and physicians. Participants expected a caring communication with the chiropractic team. Their experience was facilitated by their trust in their physician. Patients perceived the turnover of chiropractic students as a barrier to their satisfaction.

Conclusion

Our participants presented with chronic musculoskeletal pain and depressive symptoms. Our study identified facilitators and barriers for patient expectation and satisfaction with chiropractic care in a hospital setting. This study provides the first data describing the collaboration between chiropractors and physicians in France in the management of musculoskeletal disorders. These findings will inform the quality improvement of our partnership, student’s training and the development of future hospital-based collaborations integrating chiropractic care in a multidisciplinary team in France.
Quality of life assessment after total knee arthroplasty in patients with Parkinson’s disease
Authors: Zong Yaqi , Hao Congqiang , Zhang Yingjian , Wu Shuwen
Published: March 2022

Background

The number of Parkinson’s patients (PD) undergoing total knee arthroplasty (TKA) is increasing. The purpose of the study was to characterize quality of life (QOL) outcomes for patients with coexisting PD and knee osteoarthritis (KOA) following TKA.

Methods

Patients with coexisting PD and KOA undergoing TKA between June 2014 and June 2020 were included. These patients were matched to controls with KOA alone by age, gender, basic social background information and Knee society score (KSS). The primary measure was to assess the QOL by the absolute changes in the EuroQOL5-Dimensions (EQ-5D), Pain and Disability Questionnaire (PDQ), and Patient Health Questionnaire-9(PHQ-9) at the last follow-up (LFU). Secondary measures were changes in QOL that exceeded the minimum clinically important difference value (MCID). Data on the health status and QOL of all patients were collected. Simple and multivariate regression analysis was used to evaluate the impact of PD on their QOL.

Results

Twelve KOA patients with PD were compared with 48 controls. Control patients experienced QOL improvement across all three measures:EQ-5D index (0.545–0.717, P < 0.01), PDQ (81.1–52.3, P < 0.01) and PHQ-9(8.22–5.91, P < 0.01) were significantly improved at the LFU; while in patients with PD, only PDQ (91.0–81.4, P = 0.03) slightly improved. There were significant differences in the improvement of QOL between PD patients and the control group through EQ-5D (0.531 vs.0.717, P < 0.01) and PDQ (81.4vs.52.3, P < 0.01) at the LFU.

Conclusion

TKA has no benefit of QOL beyond a slight improvement in pain-related disability in the KOA patients with PD.
Asynchronous online lecture may not be an effective method in teaching cardiovascular physiology during the COVID-19 pandemic
Authors: Kositanurit Weerapat , Vivatvakin Sarocha , Kaikaew Kasiphak , Varachotisate Pachara , Burana Chuti , Chayanupatkul Maneerat , Thanprasertsuk Sekh , Wangsaturaka Danai , Kulaputana Onanong
Published: March 2022

Background

Asynchronous online lecture has become a common teaching method in medical education, especially during the COVID-19 pandemic. However, the effectiveness and students’ attitudes towards this method under this special circumstance have not been exclusively studied. Hence, we aimed to evaluate these aspects of cardiovascular physiology teaching in an undergraduate medical curriculum.

Methods

We analysed and compared the academic achievement and attitudes of 613 medical students on cardiovascular physiology between pre-COVID-19 and COVID-19 years in which different teaching methods were implemented. In addition, we also explored the importance of teaching methods and teachers by subgroup analysis to evaluate whether they influenced the academic achievement and attitudes of students.

Results

Overall students’ academic achievement was significantly higher when lectures were taught by the traditional method than by the asynchronous online method. Moreover, subgroup analysis revealed that teachers were also a factor influencing students’ academic achievement. Although most students had positive attitudes towards asynchronous online lectures, overall satisfaction was slightly higher when all lectures were taught by the traditional method than by the asynchronous online method.

Conclusions

Asynchronous online lectures might not be an effective teaching method especially during the abrupt change in education. Under the ‘new normal’ medical education, not only teaching methods but also teachers are the essential keys to the success in academic achievement and attitudes of undergraduate medical students.
An observational cohort study of health outcomes and costs associated with early pregnancy assessment units in the UK
Authors: Keeney Edna , Memtsa Maria , Goodhart Venetia , Jurkovic Davor , Ambler Gareth , Khan Nazim , Round Jeff
Published: March 2022

Background

The objective of this study was to assess the impact of consultant presence, volume of patients seen and weekend opening on the health and cost-related outcomes associated with different Early Pregnancy Assessment Unit (EPAU) configurations.

Methods

This was an observational study with a prospective cohort design. Six thousand six hundred six pregnant women (16 years of age and over) attending EPAUs because of suspected early pregnancy complications were recruited from 44 EPAUs across the UK. The main outcome measures were quality of life, costs, and anxiety.

Results

Costs, quality of life and anxiety scores were similar across configurations with little evidence to suggest an impact of consultant presence, weekend opening or volume of patients seen. Mean overall costs varied from £92 (95% CI £85 - £98) for a diagnosis of normally developing pregnancy to £1793 (95% CI £1346 - £2240) for a molar pregnancy. EQ-5D-5L score increased from 0.85 (95% CI 0.84–0.86) at baseline to 0.91 (95% CI 0.90–0.92) at 4 weeks for the 573 women who completed questionnaires at both time points, largely due to improvements in the pain/discomfort and anxiety/depression dimensions. 78% of women reported a decrease in their anxiety score immediately following their EPAU appointment.

Conclusions

EPAU configuration, as specified in this study, had limited impact on any of the outcomes examined. However, it is clear that care provided in the EPAU has a positive overall effect on women’s health and emotional wellbeing, with significant improvements in EQ-5D and anxiety shown following an EPAU visit.
Differential health impact of intervention programs for time-varying disease risk: a measles vaccination modeling study
Authors: Portnoy Allison , Hsieh Yuli Lily , Abbas Kaja , Klepac Petra , Santos Heather , Brenzel Logan , Jit Mark , Ferrari Matthew
Published: March 2022

Background

Dynamic modeling is commonly used to evaluate direct and indirect effects of interventions on infectious disease incidence. The risk of secondary outcomes (e.g., death) attributable to infection may depend on the underlying disease incidence targeted by the intervention. Consequently, the impact of interventions (e.g., the difference in vaccination and no-vaccination scenarios) on secondary outcomes may not be proportional to the reduction in disease incidence. Here, we illustrate the estimation of the impact of vaccination on measles mortality, where case fatality ratios (CFRs) are a function of dynamically changing measles incidence.

Methods

We used a previously published model of measles CFR that depends on incidence and vaccine coverage to illustrate the effects of (1) assuming higher CFR in “no-vaccination” scenarios, (2) time-varying CFRs over the past, and (3) time-varying CFRs in future projections on measles impact estimation. We used modeled CFRs in alternative scenarios to estimate measles deaths from 2000 to 2030 in 112 low- and middle-income countries using two models of measles transmission: Pennsylvania State University (PSU) and DynaMICE. We evaluated how different assumptions on future vaccine coverage, measles incidence, and CFR levels in “no-vaccination” scenarios affect the estimation of future deaths averted by measles vaccination.

Results

Across 2000–2030, when CFRs are separately estimated for the “no-vaccination” scenario, the measles deaths averted estimated by PSU increased from 85.8% with constant CFRs to 86.8% with CFRs varying 2000–2018 and then held constant or 85.9% with CFRs varying across the entire time period and by DynaMICE changed from 92.0 to 92.4% or 91.9% in the same scenarios, respectively. By aligning both the “vaccination” and “no-vaccination” scenarios with time-variant measles CFR estimates, as opposed to assuming constant CFRs, the number of deaths averted in the vaccination scenarios was larger in historical years and lower in future years.

Conclusions

To assess the consequences of health interventions, impact estimates should consider the effect of “no-intervention” scenario assumptions on model parameters, such as measles CFR, in order to project estimated impact for alternative scenarios according to intervention strategies and investment decisions.
Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children
Authors: Mitchell Cedar L. , Ngasala Billy , Janko Mark M. , Chacky Frank , Edwards Jessie K. , Pence Brian W. , Mohamed Ally , Mhamilawa Lwidiko E. , Makene Twilumba , Kyaw Thwai , Molteni Fabrizio , Mkali Humphrey , Nyinondi Ssanyu , Kabula Bilali , Serbantez Naomi , Eckert Erin L. , Kitojo Chonge , Reaves Erik , Emch Michael , Juliano Jonathan J.
Published: March 2022

Background

Transmission of malaria in sub-Saharan Africa has become increasingly stratified following decades of malaria control interventions. The extent to which environmental and land cover risk factors for malaria may differ across distinct strata of transmission intensity is not well known and could provide actionable targets to maximize the success of malaria control efforts.

Methods

This study used cross-sectional malaria survey data from a nationally representative cohort of school-aged children in Tanzania, and satellite-derived measures for environmental features and land cover. Hierarchical logistic regression models were applied to evaluate associations between land cover and malaria prevalence within three distinct strata of transmission intensity: low and unstable, moderate and seasonal, and high and perennial.

Results

In areas with low malaria transmission, each 10-percentage point increase in cropland cover was associated with an increase in malaria prevalence odds of 2.44 (95% UI: 1.27, 5.11). However, at moderate and higher levels of transmission intensity, no association between cropland cover and malaria prevalence was detected. Small associations were observed between greater grassland cover and greater malaria prevalence in high intensity settings (prevalence odds ratio (POR): 1.10, 95% UI: 1.00, 1.21), and between greater forest cover and reduced malaria prevalence in low transmission areas (POR: 0.74, 95% UI: 0.51, 1.03), however the uncertainty intervals of both estimates included the null.

Conclusions

The intensity of malaria transmission appears to modify relationships between land cover and malaria prevalence among school-aged children in Tanzania. In particular, greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities. As areas are nearing malaria elimination, it is important to re-evaluate environmental risk factors and employ appropriate interventions to effectively address low-level malaria transmission.
Addressing child health inequity through case management of under-five malaria in Nigeria: an extended cost-effectiveness analysis
Authors: Dasgupta Rishav Raj , Mao Wenhui , Ogbuoji Osondu
Published: March 2022

Background

Under-five malaria in Nigeria is a leading cause of global child mortality, accounting for 95,000 annual child deaths. High out-of-pocket medical expenditure contributes to under-five malaria mortality by discouraging care-seeking and use of effective anti-malarials in the poorest households. The significant inequity in child health outcomes in Nigeria stresses the need to evaluate the outcomes of potential interventions across socioeconomic lines.

Methods

Using a decision tree model, an extended cost-effectiveness analysis was done to determine the effects of subsidies covering the direct and indirect costs of case management of under-five malaria in Nigeria. This analysis estimates the number of child deaths averted, out-of-pocket (OOP) expenditure averted, cases of catastrophic health expenditure (CHE) averted, and cost of implementation. An optimization analysis was also done to determine how to optimally allocate money across wealth groups using different combinations of interventions.

Results

Fully subsidizing direct medical, non-medical, and indirect costs could annually avert over 19,000 under-five deaths, 8600 cases of CHE, and US$187 million in OOP spending. Per US$1 million invested, this corresponds to an annual reduction of 76 under-five deaths, 34 cases of CHE, and over US$730,000 in OOP expenditure. Due to low initial treatment coverage in poorer socioeconomic groups, health and financial-risk protection benefits would be pro-poor, with the poorest 40% of Nigerians accounting for 72% of all deaths averted, 55% of all OOP expenditure averted, and 74% of all cases of CHE averted. Subsidies targeted to the poor would see greater benefits per dollar spent than broad, non-targeted subsidies. In an optimization scenario, the strategy of fully subsidizing direct medical costs would be dominated by a partial subsidy of direct medical costs as well as a full subsidy of direct medical, nonmedical, and indirect costs.

Conclusion

Subsidizing case management of under-five malaria for the poorest and most vulnerable would reduce illness-related impoverishment and child mortality in Nigeria while preserving limited financial resources. This study is an example of how focusing a targeted policy-intervention on a single, high-burden disease can yield large health and financial-risk protection benefits in a low and middle-income country context and address equity consideration in evidence-informed policymaking.
Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression
Authors: Xian Xian , Cai Li-Li , Li Yang , Wang Ran-Chao , Xu Yu-Hao , Chen Ya-Jie , Xie Yu-Hang , Zhu Xiao-Lan , Li Yue-Feng
Published: March 2022

Background

Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury.

Results

By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode.

Conclusion

MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Graphical Abstract
The impact of the COVID-19 pandemic on illicit drug supply, drug-related behaviour of people who use drugs and provision of drug related services in Georgia: results of a mixed methods prospective cohort study
Authors: Otiashvili David , Mgebrishvili Tamar , Beselia Ada , Vardanashvili Irina , Dumchev Kostyantyn , Kiriazova Tetiana , Kirtadze Irma
Published: March 2022

Background

This study examines the effects of COVID-19 related restrictions on the supply of illicit drugs, drug-use behaviour among people who use drugs (PWUD) regularly (at least weekly), and drug-related service provision in Tbilisi, Georgia.

Methodology

In this mixed methods study, a cohort of 50 Georgian PWUD recruited through a snow-ball sampling participated in a bi-weekly online survey in April–September, 2020. They also took part in the qualitative telephone interviews at 12- and 24-week follow-up time points. In addition, four key informants (field experts) were interviewed monthly to assess their perceptions of changes in the illicit drug market and drug service delivery.

Results

Mean age in the sample was 36 (range 18–60); 39 (78%) were males. Perceived availability of drugs was reduced during the lockdown, and many PWUD switched to alternative substances when preferred drugs were not available. On average, participants used significantly fewer substances over the course of the study, from 3.5 substances in the preceding 14 days to 2.1 (aOR 0.92; 95% CI 0.90–0.94). Consumption of cannabis products declined significantly (aOR 0.89; 95% CI 0.84–0.95), likewise alcohol (aOR 0.94; 95% CI 0.88–1.0), diverted medicinal methadone (aOR 0.85; 95% CI 0.8–0.9) and diverted medicinal buprenorphine (aOR 0.91; 95% CI 0.84–0.99). PWUD cited fewer contacts with drug dealers, the lack of transportation, and the lack of conventional recreational environment as the main reasons for these changes. When access to sterile injection equipment was limited, PWUD exercised risk-containing injection behaviours, such as buying drugs in pre-filled syringes (aOR 0.88; 95% CI 0.80–0.96). Harm reduction and treatment programs managed to adopt flexible strategies to recover services that were affected during the initial stage of the pandemic.

Conclusions

COVID-19-related restrictive measures mediated specific changes in supply models and drug-use behaviours. While adjusting to the new environment, many PWUD would engage in activities that put them under increased risk of overdose and blood-borne infections. Harm reduction and treatment services need to develop and implement protocols for ensuring uninterrupted service delivery during lockdowns, in anticipation of the similar epidemics or other emergency situations.
Methodological issues on “Stakeholder attitudes to the regulation of traditional and complementary medicine professions: a systematic review”
Authors: Shirzad Meysam , Abbassian Alireza
Published: March 2022

Systematic reviews cling to the doctrine that science has an updating databank and attempt to identify all available evidence by featured eligibility criteria to find the answer to a unique scientific question. Therefore, to reach this aim, these researches should use a wise method and comprehensive search strategy, as they are widely used to guide clinical and political decisions and the establishment of future researches. We would like to appreciate Jenny Carè, Amie Steel, and Jon Wardle for the valuable article “Stakeholder attitudes to the regulation of traditional and complementary medicine professions: a systematic review”. Some important missed search terms in the field of traditional medicine names and traditional and complementary medicine (T&CM) regulation concepts were discussed in the article.
Adherence to facemask use in public places during the autumn–winter 2020 COVID-19 lockdown in Greece: observational data
Authors: Fountoulakis Konstantinos N. , Breda Joao , Arletou Marianna P. , Charalampakis Anastasios I. , Karypidou Maria G. , Kotorli Konstantina S. , Koutsoudi Christina G. , Ladia Eleftheria S. , Mitkani Calypso A. , Mpouri Vasiliki N. , Samara Anastasia C. , Stravoravdi Aikaterini S. , Tsiamis Ioannis G. , Tzortzi Aphrodite , Vamvaka Maria A. , Zacharopoulou Charikleia N. , Prezerakos Panagiotis E. , Koupidis Sotirios A. , K. Fountoulakis Nikolaos , Tsapakis Eva Maria , Konsta Anastasia , Theodorakis Pavlos N.
Published: March 2022

Background

Wearing facemasks is of proven efficacy as a public health protective measure against COVID-19. Currently there are no observational data concerning the wearing of facemasks and the adherence to guidelines concerning their handling.

Methods

Registration of the way passers-by were wearing facemasks at 26 different locations of five major cities in Greece. The results were correlated with the rate of COVID-19 deaths in the region.

Results

In total, 119,433 passers-by were registered, 57,043 females (47.8%) and 62,390 males (52.2%). From the total sample, 81.1% were wearing the mask properly, 10.8% had their nose out, 6.2% were wearing it under the jaw, and 1.9% had no mask at all . There was a significant difference between males and females concerning any use of mask. Inappropriate use of was correlated with COVID-19 death rate in the studied region.

Conclusion

Our findings suggest that under conditions of mandatory wearing and in central locations of major cities, during walking, proper use of masks is suboptimal, but still contributes with some protection. Fear and risk perception seem to be strong factors contributing to adherence to proper mask wearing.
Preferences for different features of ENDS products by tobacco product use: a latent class analysis
Authors: Enyioha Chineme , Boynton Marcella H. , Ranney Leah M. , Byron M. Justin , Goldstein Adam O. , Kistler Christine E.
Published: March 2022

Background

From a public health perspective, electronic nicotine delivery devices (ENDS) use may be beneficial for some populations (e.g., smokers who fully switch to ENDS) but detrimental for others (e.g., nonsmokers). Understanding the importance placed on different ENDS product features by user groups can guide interventions and regulations.

Methods

Participants were US adults who had used ENDS at least once and from a convenience sample drawn from a market research software in 2016. Participants chose between 9 different ENDS product features (harms of use, general effects of use, use as a cessation aid, initial purchase price, monthly cost, nicotine content, flavor availability, device design, and modifiability). A latent class analysis (LCA) identified subgroups of feature preferences and examined differences between groups by socio-demographics and tobacco product use.

Results

Of the 636 participants, 81% were White, the median age was 42, and 65% were current cigarette smokers. The LCA identified a 4-class solution as the most appropriate model: (1) people with high nicotine dependence who preferred ENDS similar to combustible cigarettes, (2) people with moderate tobacco use who were interested in low nicotine ENDS (3) people who use ENDS and combustible tobacco who preferred lower price and flavored ENDS products, and (4) people who used ENDS predominantly, without a strong preference for any of the features presented.

Conclusions

Tobacco use classes were associated with differences in preferences for ENDS features. These findings can inform regulations to reduce ENDS use among specific groups of people who use ENDS products.
Optimal management of recurrent and metastatic upper tract urothelial carcinoma: Implications of intensity modulated radiation therapy
Authors: Kim Mi Sun , Koom Woong Sub , Cho Jae Ho , Kim Se-Young , Lee Ik Jae
Published: March 2022

Background

Upper tract urothelial carcinoma (UTUC) is rare and the treatment for recurrent or metastatic UTUC is unclear. We evaluated the outcomes of salvage and palliative radiotherapy (RT) and prognostic factors in UTUC patients and find implications for salvage and palliative RT.

Methods

Between August 2006 and February 2021, 174 patients (median age, 68 years; range, 37–90) underwent salvage and palliative RT. Disease status at RT included initially diagnosed advanced disease (n = 8, 4.6%), local recurrence only (n = 56, 32.2%), distant metastasis only (n = 59, 33.9%), and local recurrence and distant metastasis (n = 51, 29.3%). The primary tumor location included the renal pelvis (n = 87, 50%), ureter (n = 77, 44.3%), and both (n = 10, 5.7%). Radical nephroureterectomy, chemotherapy, and immunotherapy were used in 135 (77.6%), 101 (58%), and 19 (10.9%) patients, respectively. Survival outcomes and prognostic factors were analysed using Cox and logistic regression analysis.

Results

Salvage RT and palliative RT was administered in 73 (42%) and 101 (58%) patients, respectively. The median radiation dose was 45 Gy (range, 15–65). Two-dimensional (2D) or three-dimensional (3D) RT and intensity modulated RT (IMRT) were used in 61 (35.1%) and 113 (64.9%) patients, respectively. The median follow-up was 7.8 months. The median duration of overall survival (OS) was 13.4 months, and the 1-year OS was 53.5%. The median progression-free survival (PFS) was 4.7 months, and the 6-month PFS was 41.9%. The 6-month infield PFS was 84%. In multivariate analysis, RT method (2D/3D vs. IMRT, p = 0.007) and RT response (p = 0.008) were independent prognostic factors for OS, and RT response correlated with PFS (p = 0.015). In subgroup analysis in patients with PD-L1 data, positive PD-L1 correlated with better PFS (p = 0.009). RT response-associated factors were concurrent chemotherapy (p = 0.03) and higher radiation dose (p = 0.034). Of 145 patients, 10 (6.9%) developed grade 3 acute or late toxicity.

Conclusions

Salvage and palliative RT for UTUC are feasible and effective. Patients with RT response using IMRT may have survival benefit from salvage and palliative RT. Positive PD-L1 status might be related to radiosensitivity. High-dose radiation with concurrent chemotherapy may improve RT response.