Clinical Features of Severe Malaria Associated with Death: A 13-Year Observational Study in The Gambia

Background

Severe malaria (SM) is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management.

Methods

A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae.

Findings

Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7–7.3]), respiratory distress (OR 2.4 [95%CI, 1.7–3.2]), hypoglycemia (OR 1.7 [95%CI, 1.2–2.3]), jaundice (OR 1.9 [95%CI, 1.2–2.9]) and renal failure (OR 11.1 [95%CI, 3.3–36.5]) were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60–0.65]) and impaired consciousness (AUC 0.61[95%CI, 0.59–0.63]), which were comparable to the ability of hyperlactatemia (blood lactate>5 mM) to predict death (AUC 0.64 [95%CI, 0.55–0.72]). A Blantyre coma score (BCS) of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68–0.72]), and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67–0.76]).The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71–0.76]).

Conclusion

The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM.     

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.     

Potential Risk Factors of Persistent Low Back Pain Developing from Mild Low Back Pain in Urban Japanese Workers

Study Design

Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study in urban settings were used for this analysis.

Objective

To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain.

Summary of Background Data

Although psychosocial factors are strongly indicated as yellow flags of low back pain (LBP) leading to disability, the association between aggravated LBP and psychosocial factors has not been well assessed in Japanese workers.

Methods

At baseline, 5,310 participants responded to a self-administered questionnaire including questions about individual characteristics, ergonomic work demands, and work-related psychosocial factors (response rate: 86.5%), with 3,811 respondents completing the 1-year follow-up questionnaire. The target outcome was aggravation of mild LBP into persistent LBP during the follow-up period. Incidence was calculated for the participants with mild LBP during the past year at baseline. Logistic regression was used to explore risk factors associated with persistent LBP.

Results

Of 1,675 participants who had mild LBP during the preceding year, 43 (2.6%) developed persistent LBP during the follow-up year. Multivariate analyses adjusted for individual factors and an ergonomic factor found statistically significant or almost significant associations of the following psychosocial factors with persistent LBP: interpersonal stress at work [adjusted odds ratio (OR): 1.96 and 95% confidence interval (95%CI): 1.00–3.82], job satisfaction (OR: 2.34, 95%CI: 1.21–4.54), depression (OR: 1.92, 95%CI: 1.00–3.69), somatic symptoms (OR: 2.78, 95%CI: 1.44–5.40), support from supervisors (OR: 2.01, 95%CI: 1.05–3.85), previous sick-leave due to LBP (OR: 1.94, 95%CI: 0.98–3.86) and family history of LBP with disability (OR: 1.98, 95%CI: 1.04–3.78).

Conclusions

Psychosocial factors are important risk factors for persistent LBP in urban Japanese workers. It may be necessary to take psychosocial factors into account, along with physical work demands, to reduce LBP related disability.     

Peptic Ulcer Disease in Healthcare Workers: A Nationwide Population-Based Cohort Study

Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on-call, and have rotating nightshifts, all of which might contribute to peptic ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not clear. Using Taiwan’s National Health Insurance Research Database, we identified 50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs (dieticians, technicians, rehabilitation therapists, and social workers) as the study cohort, and randomly selected an identical number of non-HCW patients (i.e., general population) as the comparison cohort. Conditional logistical regression analysis was used to compare the PUD risk between them. Subgroup analysis for physician specialties was also done. Nurses and other HCWs had a significantly higher PUD risk than did the general population (odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.433–1.521 and OR: 1.328; 95% CI: 1.245–1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828–0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI: 0.987–1.072). In the physician specialty subgroup analysis, internal medicine, surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other physicians (OR: 1.579; 95% CI: 1.441–1.731, OR: 1.734; 95% CI: 1.565–1.922, OR: 1.336; 95% CI: 1.151–1.550, and OR: 1.615; 95% CI: 1.425–1.831, respectively). In contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359–0.822). Heavy workloads, long working hours, workplace stress, rotating nightshifts, and coping skills may explain our epidemiological findings of higher risks for PUD in some HCWs, which might help us improve our health policies for HCWs.     

Patients’ Experiences with and Attitudes towards a Diabetes Patient Web Portal

ObjectiveA diabetes patient web portal allows patients to access their personal health record and may improve diabetes outcomes; however, patients’ adoption is slow. We aimed to get insight into patients’ experiences with a web portal to understand how the portal is being used, how patients perceive the content of the portal and to assess whether redesign of the portal might be needed.Results632 patients (42.1%) returned the questionnaire. Their mean age was 59.7 years, 63.1% was male and 81.8% had type 2 diabetes. 413 (65.3%) people were persistent users and 34.7% early quitters. In the multivariable analysis, insulin use (OR2.07; 95%CI[1.18–3.62]), experiencing more frequently hyperglycemic episodes (OR1.30;95%CI[1.14–1.49]) and better diabetes knowledge (OR1.02, 95%CI[1.01–1.03]) do increase the odds of being a persistent user. Persistent users perceived the usefulness of the patient portal significantly more favorable. However, they also more decisively declared that the patient portal is not helpful in supporting life style changes. Early quitters felt significantly more items not applicable in their situation compared to persistent users. Both persistent users (69.8%) and early quitters (58.8%) would prefer a reminder function for scheduled visits. About 60% of both groups wanted information about medication and side-effects in their portal.ConclusionsThe diabetes patient web portal might be improved significantly by taking into account the patients’ experiences and attitudes. We propose creating separate portals for patients on insulin or not.     

Prognostic Significance of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20–1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31–2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97–1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52–1.74), relapse risk (RR, 1.12; 95% CI, 0.90–1.41) or OS (RR, 1.03; 95% CI, 0.90–1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02–4.05), relapse risk (RR, 1.89; 95%CI: 1.51–2.37) and OS (RR, 2.26; 95%CI: 1.35–3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19–1.95) or OS (RR, 1.12; 95%CI: 0.90–1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings.     

Susceptibility to Transmitting HIV in Patients Initiating Antiretroviral Therapy in Rural District Hospitals in Cameroon (Stratall ANRS 12110/ESTHER Trial)

Objectives

Using cohort data nested in a randomized trial conducted in Cameroon, this study aimed to investigate time trends and predictors of the susceptibility to transmitting HIV during the first 24 months of treatment.

Methods

The outcome, susceptibility to transmitting HIV, was defined as reporting inconsistent condom use and experiencing incomplete virological suppression. Mixed logistic regressions were performed to identify predictors of this outcome among 250 patients reporting to have had sexual relationships either with HIV-negative or unknown HIV status partner(s).

Results

Despite an initial decrease from 76% at M0 to 50% at M6, the rate of inconsistent condom use significantly increased from M12 (59%) to M24 (66%) (p = 0.017). However, the proportion of patients susceptible to transmitting HIV significantly decreased over follow-up from 76% at M0, to 50% at M6, 31% at M12 and 27% at M24 (p<0.001). After controlling for age, gender and intervention group, we found that perceiving healthcare staff’s readiness to listen as poor (adjusted odds ratios (AOR) [95% Confidence Interval (CI)] = 1.87 [1.01–3.46]), reporting to have sexual relationships more than once per week (AOR [95%CI] = 2.52 [1.29–4.93]), having more than one sexual partner (AOR [95%CI] = 2.53 [1.21–5.30]) and desiring a/another child (AOR [95%CI] = 2.07 [1.10–3.87]) were all associated with a higher risk of being susceptible to transmitting HIV. Conversely, time since ART initiation (AOR [95%CI] = 0.66 [0.53–0.83] for an extra 6 months and ART adherence (AOR [95%CI] = 0.33 [0.15–0.72]) were significantly associated with a lower risk of being susceptible to transmitting HIV.

Conclusions

The decrease observed in the susceptibility to transmitting HIV suggests that fear of behavioural disinhibition should not be a barrier to universal access to ART. However, developing adequate preventive interventions matching patients’ expectations -like the desire to have children- and strengthening healthcare staff’s counselling skills are urgently needed to maximize the impact of ART in slowing the HIV epidemic.     

Risk Factors for Hospitalization Due to Community-Acquired Sepsis – A Population-Based Case-Control Study

Background

The aim of the study was to estimate risk factors for hospitalization due to sepsis and to determine whether these risk factors vary by age and gender.

Methods

We performed a population-based case-control study of all adult patients admitted to a medical ED from September 2010 to August 2011. Controls were sampled within the hospital catchment-area. All potential cases were manually validated using a structured protocol. Vital signs and laboratory values measured at arrival were registered to define systemic inflammatory response syndrome and organ dysfunction. Multivariable logistic regression was used to elucidate which predefined risk factors were associated with an increased or decreased risk hospitalization due to sepsis.

Results

A total of 1713 patients were admitted with sepsis of any severity. The median age was 72 years (interquartile range: 57–81 years) and 793 (46.3%) were male. 621 (36.3%) patients were admitted with sepsis, 1071 (62.5%) with severe sepsis and 21 (1.2%) with septic shock. Episodes with sepsis of any severity were associated with older age (85+ years adjusted OR 6.02 [95%CI: 5.09–7.12]), immunosuppression (4.41 [3.83–5.09]), alcoholism-related conditions (2.90 [2.41–3.50]), and certain comorbidities: psychotic disorder (1.90 [1.58–2.27]), neurological (1.98 [1.73–2.26]), respiratory (3.58 [3.16–4.06]), cardiovascular (1.62 [1.41–1.85]), diabetes (1.82 [1.57–2.12]), cancer (1.44 [1.22–1.68]), gastrointestinal (1.71 [1.44–2.05]) and renal (1.46 [1.13–1.89]). The strength of the observed associations for comorbid factors was strongest among younger individuals.

Conclusions

Hospitalization due to sepsis of any severity was associated with several independent risk factors, including age and comorbid factors.     

Risk Factors of Post-Traumatic Stress Disorder (PTSD) after Wenchuan Earthquake: A Case Control Study

Background

Few clues were found in the literature about the independent risk factors for PTSD among earthquake survivors in Sichuan province three years after the 2008 earthquake. Ours was the first case-control study with matching factors of age and distance from the epicenter among survivors age 16 years or older, three years after the catastrophe.

Objectives

To identify independent risk factors for PTSD among earthquake survivors.

Methods

We performed a population-based matched case-control study. The cases were drawn from earthquake areas three years after the Wenchuan earthquake, including 113 cases who met positive criteria for PTSD symptoms according to the PCL-C (PTSD Checklist-Civilian Version) score and 452 controls who did not meet the criteria. Cases and controls were matched individually by birth year (+ three years) and the town they lived in when the earthquake occurred.

Results

Independent risk factors for PTSD symptoms included two-week disease prevalence (odds ratio [OR],1.92; 95% confidence interval [CI],1.18–3.13), witnessing someone being killed in the earthquake (OR, 2.04;95%CI, 1.17–3.58), having no regular income after the earthquake (OR, 0.52; 95%CI, 0.28–0.98), receiving mental health support only one time after the earthquake (OR, 2.43; 95%CI, 1.09–5.42) and lower social support (lower PSSS score) (OR, 0.95; 95%CI, 0.93–0.97).

Conclusion

Earthquake experience, suffering from physical illnesses, lack of stable income, and lower social support were associated with PTSD symptoms.     

Workplace Social Capital and Mental Health among Chinese Employees: A Multi-Level,Cross-Sectional Study

Background

Whereas the majority of previous research on social capital and health has been on residential neighborhoods and communities, the evidence remains sparse on workplace social capital. To address this gap in the literature, we examined the association between workplace social capital and health status among Chinese employees in a large, multi-level, cross-sectional study.

Methods

By employing a two-stage stratified random sampling procedure, 2,796 employees were identified from 35 workplaces in Shanghai during March to November 2012. Workplace social capital was assessed using a validated and psychometrically tested eight-item measure, and the Chinese language version of the WHO-Five Well-Being Index (WHO-5) was used to assess mental health. Control variables included sex, age, marital status, education level, occupation status, smoking status, physical activity, and job stress. Multilevel logistic regression analysis was conducted to explore whether individual- and workplace-level social capital was associated with mental health status.

Results

In total, 34.9% of workers reported poor mental health (WHO-5<13). After controlling for individual-level socio-demographic and lifestyle variables, compared to workers with the highest quartile of personal social capital, workers with the third, second, and lowest quartiles exhibited 1.39 to 3.54 times greater odds of poor mental health, 1.39 (95% CI: 1.10–1.75), 1.85 (95% CI: 1.38–2.46) and 3.54 (95% CI: 2.73–4.59), respectively. Corresponding odds ratios for workplace-level social capital were 0.95 (95% CI: 0.61–1.49), 1.14 (95% CI: 0.72–1.81) and 1.63 (95% CI: 1.05–2.53) for the third, second, and lowest quartiles, respectively.

Conclusions

Higher workplace social capital is associated with lower odds of poor mental health among Chinese employees. Promoting social capital at the workplace may contribute to enhancing employees’ mental health in China.     

Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

Objectives

The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).

Methods

This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).

Results

The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.

Conclusions

EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034929","term_id":"NCT02034929"}}NCT02034929.     

Prevalence and Associated Factors of Myopia in High-School Students in Beijing

Purpose

To evaluate prevalence and associated factors for myopia in high school students in Beijing.

Methods

Grade 10 and 11 high school students were randomly selected from nine randomly selected districts of Beijing. The students underwent non-cylcoplegic auto-refractometry and an interview.

Results

Out of 4798 eligible students, 4677 (93.4%) students (mean age:16.9±0.7years;range:16–18 years) participated. Mean refractive error of right eyes and left eyes was −2.78±2.29 diopters and −2.59±2.50 diopters, respectively. Prevalence of myopia (defined as ≤ −1.00 diopters in the worse eye) was 80.7% (95% Confidence Interval (CI): 79.6–81.8%). Out of 3773 students with myopia, 1525 (40.4%) wore glasses daily. In multiple logistic regression analysis, a higher prevalence of myopia was associated with female sex (odds ratio (OR) = 1.31;95%CI:1.11–1.55), Han ethnicity (OR = 1.64;95%CI:1.28–2.11), attending key schools (OR = 1.48;95%CI:1.24,1.77), higher family income (OR = 1.37;95%CI:1.09–1.71), longer time spent for near work (OR = 1.43;95%CI:1.06–1.93), shorter near work distance (OR = 1.87;95%CI:1.55–2.26), lower frequency of active rest during studying (OR = 1.40;95%CI:1.16–1.70), and parental myopia (OR = 2.28;95%CI:1.80–2.87). The interaction between distance from near work and time spent for near work was statistically (P = 0.03) significant. In multiple logistic regression analysis, higher prevalence of high myopia (≤-6.0 diopters) was associated with studying in key schools (OR = 1.38;95%CI:1.05,1.81), lower frequency of active rest during studying (OR = 1.40;95%CI:1.09,1.79), and a higher number of myopic parents (OR = 2.66;95%CI:2.08,3.40).

Conclusions

A prevalence of about 80% for myopia and a prevalence of about 10% for high myopia in students aged 16 to 18 years and attending classes of grade 10 and 11 in a Chinese metropolitan region is another example of the high prevalence of moderate and high myopia in metropolitan areas of China. With this young myopic generation getting older, myopia as cause for visual impairment and blindness may further increase in importance. Future studies may address whether active rests during studying with looking into the distance are preventive against myopia development or progression.     

Risk Factors for Death from Influenza A(H1N1)pdm09, State of S?o Paulo,Brazil, 2009

This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28^th and August 29^th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.     

Effects of physical activity on the progression of diabetic nephropathy: a meta-analysis

Background: Diabetic nephropathy (DN) is an important microvascular complication of diabetes. Physical activity (PA) is part of a healthy lifestyle for diabetic patients; however, the role of PA in DN has not been clarified. Our aim was to conduct a meta-analysis to explore the association between PA and DN risk.Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched for articles examining PA in diabetic patients and its effect on renal function. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study protocol is registered with PROSPERO (CRD42020191379).Results: A total of 38991 participants were identified from 18 studies. The results indicated that PA was associated with increases in the glomerular filtration rate (SMD = 0.01, 95% CI = [0.02–0.17]) and decreases in the urinary albumin creatinine ratio (SMD = −0.53, 95% CI: −0.72 to −0.34), rate of microalbuminuria (OR = 0.61, 95% CI = [0.46–0.81]), rate of acute kidney injury (OR = 0.02, 95% CI = [0.01–0.04]), rate of renal failure (OR = 0.71, 95% CI = [0.52–0.97]) and risk of DN in patients with Type 1 diabetes (OR = 0.67, 95% CI = [0.51–0.89]).Conclusions: This meta-analysis indicated that PA is effective for improving DN and slowing its progression; however, more high-quality randomized controlled trials are required on this topic.     

Efficacy of Mesenchymal Stem Cell Therapy for Steroid-Refractory Acute Graft-Versus-Host Disease following Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Background

Mesenchymal stem cells (MSCs) have been broadly used experimentally in various clinical contexts. The addition of MSCs to initial steroid therapy for acute graft-versus-host disease (aGVHD) may improve patient outcomes. However, investigations regarding prognostic factors affecting the efficacy of MSC therapy for steroid-refractory aGVHD remain controversial. We thus conducted a systematic review and meta-analysis of published clinical trials to determine possible prognostic factors affecting the efficacy of MSCs in treating steroid-refractory aGVHD.

Methods and Findings

Clinical trials using MSC therapy for steroid-refractory aGVHD were identified by searching PubMed and EMBASE databases. A total of 6,963 citations were reviewed, and 13 studies met the inclusion criteria. A total of 301 patients from thirteen studies were included. Of these, 136 patients showed a complete response (CR), and 69 patients displayed a partial (PR) or mixed response (MR). In total, 205 patients exhibited overall response (ORR). Patients with skin steroid-refractory aGVHD showed a better clinical response than gastrointestinal (CR: odds ratio [OR] = 1.93, 95% confidence interval [95%CI]: 1.05–3.57, p < 0.05) and liver (CR: OR = 2.30, 95%CI: 1.12–4.69, p < 0.05, and ORR: OR = 2.93, 95%CI: 1.06–8.08, p < 0.05) steroid-refractory aGVHD. Those with grade II steroid-refractory aGVHD exhibited a better clinical response following MSC therapy than recipients with grade III–IV (CR: OR = 3.22, 95%CI: 1.24–8.34, p < 0.05). Completion therapy may improve the CR but reduce ORR compared with induction therapy (CR: OR = 0.20, 95%CI: 0.09–0.44, p < 0.05; ORR: OR = 2.18, 95%CI: 1.17–4.05, p = 0.01). There was also a trend towards a better clinical response in children compared with adults (CR: OR = 2.41, 95%CI: 1.01–5.73, p = 0.05).

Conclusions

Age, skin involvement, lower aGVHD grade, and the number of infusions are the main prognostic factors affecting the efficacy of MSC therapy for steroid-refractory aGVHD.     

Clinical Background of Patients with Sperm in Their Urinary Sediment

Introduction

The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice.

Aims

The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples.

Methods

We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged ≥20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines.

Main Outcomes

In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%).

Results

Multivariate analysis demonstrated that younger age (<65) (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.32–2.21), the total number of examinations (≥4) (OR: 1.46, 95%CI: 1.11–1.92), diabetes (OR: 1.72, 95%CI: 1.31–2.25), a history of pelvic surgery for colon cancer (OR: 4.89, 95%CI: 2.38–10.02), alpha-1 blocker use (OR: 1.55, 95%CI: 1.16–2.08), a history of trans-urethral resection of the prostate (OR: 2.77, 95%CI: 1.46–5.13), and selective serotonin reuptake inhibitor use (OR: 2.12, 95%CI: 1.07–4.19) were independent predictors of the presence of at least one sperm in urinary sediment.

Conclusion

There is considerable overlap between the factors associated with the presence of at least one sperm in urinary sediment and those that are strongly associated with ejaculatory disorders.     

Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review

Aims/Hypothesis

Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.

Methods

Data source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.

Results

Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74–0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36–0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76–0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83–0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.

Conclusions/Interpretation

Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.     

Epidemiology of Severe Acute Respiratory Illness (SARI) among Adults and Children Aged ≥5 Years in a High HIV-Prevalence Setting, 2009–2012

ObjectiveThere are few published studies describing severe acute respiratory illness (SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged ≥5 years in South Africa.MethodsWe conducted prospective surveillance for individuals with SARI from 2009–2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators.FindingsWe enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9% (600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13–19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR):1.7; 95%CI:1.1–2.7), have pneumococcal infection (OR 2.4; 95%CI:1.7–3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95%CI:1.2–2.2) and had a higher case-fatality ratio (8% vs 5%;OR1.7; 95%CI:1.2–2.3), but were less likely to be infected with influenza (OR 0.6; 95%CI:0.5–0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8;95%CI:1.3–2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95%CI:1.3–32.0) and supplemental-oxygen therapy (OR 2.6; 95%CI:2.1–3.2).ConclusionThe burden of hospitalized SARI amongst individuals aged ≥5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.     

Clinical Risk Scoring Models for Prediction of Acute Kidney Injury after Living Donor Liver Transplantation: A Retrospective Observational Study

Acute kidney injury (AKI) is a frequent complication of liver transplantation and is associated with increased mortality. We identified the incidence and modifiable risk factors for AKI after living-donor liver transplantation (LDLT) and constructed risk scoring models for AKI prediction. We retrospectively reviewed 538 cases of LDLT. Multivariate logistic regression analysis was used to evaluate risk factors for the prediction of AKI as defined by the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage). Three risk scoring models were developed in the retrospective cohort by including all variables that were significant in univariate analysis, or variables that were significant in multivariate analysis by backward or forward stepwise variable selection. The risk models were validated by way of cross-validation. The incidence of AKI was 27.3% (147/538) and 6.3% (34/538) required postoperative renal replacement therapy. Independent risk factors for AKI by multivariate analysis of forward stepwise variable selection included: body-mass index >27.5 kg/m² [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.32–4.55], serum albumin <3.5 mg/dl (OR 1.76, 95%CI 1.05–2.94), MELD (model for end-stage liver disease) score >20 (OR 2.01, 95%CI 1.17–3.44), operation time >600 min (OR 1.81, 95%CI 1.07–3.06), warm ischemic time >40 min (OR 2.61, 95%CI 1.55–4.38), postreperfusion syndrome (OR 2.96, 95%CI 1.55–4.38), mean blood glucose during the day of surgery >150 mg/dl (OR 1.66, 95%CI 1.01–2.70), cryoprecipitate > 6 units (OR 4.96, 95%CI 2.84–8.64), blood loss/body weight >60 ml/kg (OR 4.05, 95%CI 2.28–7.21), and calcineurin inhibitor use without combined mycophenolate mofetil (OR 1.87, 95%CI 1.14–3.06). Our risk models performed better than did a previously reported score by Utsumi et al. in our study cohort. Doses of calcineurin inhibitor should be reduced by combined use of mycophenolate mofetil to decrease postoperative AKI. Prospective randomized trials are required to address whether artificial modification of hypoalbuminemia, hyperglycemia and postreperfusion syndrome would decrease postoperative AKI in LDLT.