Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

OBJECTIVES: Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. METHODS: We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. RESULTS: From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. CONCLUSION: People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

Musculoskeletal disorders and pain in agricultural workers in Low- and Middle-Income Countries: a systematic review and meta-analysis.

Agricultural workers constitute two-thirds of the population of Low- and Middle-Income Countries (LMIC) and are at increased risk of developing musculoskeletal disorders (MSD) due to high-risk activities. This systematic review and meta-analysis aim to synthesise the prevalence, predictors, and outcomes of musculoskeletal pain amongst agricultural workers to identify priority areas for prevention and development of early interventions. This systematic review and meta-analysis included Studies published from the inception of global electronic databases until 30 September 2022 were included. Prevalence estimates for MSDs among agricultural workers aged over 18 years in LMIC were extracted. Narrative synthesis summarized study findings and pooled estimates for 12-month pain prevalence were calculated. 7502 potential studies were identified. 64 studies (68,684 participants from 23 countries) were included in the systematic review; 33 studies were included in the meta-analysis. Low back pain was the most widely investigated symptom. The 12-month pooled prevalence of low back pain was highest in Africa [61.96% (45.69-76.22)] compared to Asia [54.16% (47.76-60.50)] and South/Central America [28.52%(10.91-50.33)]. Narrative synthesis found associations between MSDs, particular activities including heavy lifting and repetitive movements, and outcomes including reduced productivity. MSDs are common in agriculture workers in LMIC. Global prevalence of low back pain in farmers, particularly in Africa, is greater than in previously reported global prevalence in the general population. This may be attributed to environmental factors and high-risk activities which could be targeted for prevention and early intervention strategies to support individuals, prevent disability, and reduce loss of productivity.

The relationship between pain and depression and anxiety in patients with inflammatory arthritis: a systematic review protocol.

Pain is a major challenge for patients with inflammatory arthritis (IA). Depression and anxiety are common comorbidities in IA, associating with worse outcomes. How they relate to pain is uncertain, with existing systematic reviews (a) mainly considering cross-sectional studies, (b) focusing on the relationship between pain and mental health in the context of disease activity/quality of life, and (c) not specifically considering the impact of treating depression/anxiety on pain. This PROSPERO-registered (CRD42023411823) systematic review will address this knowledge-gap by synthesizing evidence to summarise the associations (and potential mediators) between pain and depression/anxiety and evaluate the impact of treating co-morbid depression/anxiety on pain in IA. Relevant databases will be searched, articles screened and their quality appraised (using Joanna Briggs Institute critical appraisal tools) by two reviewers. Eligible studies will include adults with rheumatoid arthritis or spondyloarthritis, be a clinical trial or observational study, and either (a) report the relationship between pain and depression/anxiety (observational studies/baseline trials), or (b) randomise participants to a pharmacological or psychological treatment to manage depression/anxiety with a pain outcome as an endpoint (trials). To synthesise data on the association between pain and depression/anxiety, where available adjusted coefficients from regression models will be pooled in a random-effects meta-analysis. A synthesis without meta-analysis will summarise mediators. To evaluate the impact of treating depression/anxiety on pain, endpoint mean differences between treatment arms will be combined in a random-effects meta-analysis. Through understanding how depression/anxiety contribute to pain in IA, our review has the potential to help optimise approaches to IA pain.

Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink.

OBJECTIVES: To determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout. METHODS: We conducted two matched retrospective cohort studies in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with (1) colchicine or (2) NSAID prophylaxis were compared with those initiating without prophylaxis, individually matched by age, sex and propensity to receive the relevant prophylaxis. Weighted Cox proportional hazards models investigated associations between colchicine/NSAID and specified adverse events. RESULTS: 13 945 individuals prescribed colchicine were matched to 13 945 with no prophylaxis and 25 980 prescribed NSAID to 25 980 with no prophylaxis. Adverse event incidence rates were <200/10 000 patient-years except diarrhoea (784.4; 95% CI 694.0 to 886.5) and nausea (208.1; 95% CI 165.4 to 261.7) for colchicine and angina for NSAID (466.6; 95% CI 417.2 to 521.8). Diarrhoea (HR 2.22; 95% CI 1.83 to 2.69), myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17), neuropathy (4.75; 95% CI 1.20 to 18.76), myalgia (2.64; 95% CI 1.45 to 4.81), bone marrow suppression (3.29; 95% CI 1.43 to 7.58) and any adverse event (1.91, 95% CI 1.65 to 2.20) were more common with colchicine than no prophylaxis, but not nausea/vomiting (1.34; 95% CI 0.97 to 1.85). Angina (1.60; 95% CI 1.37 to 1.86), acute kidney injury (1.56; 95% CI 1.20 to 2.03), MI (1.89; 95% CI 1.44 to 2.48), peptic ulcer disease (1.67; 95% CI 1.14 to 2.44) and any adverse event (1.63; 95% CI 1.44 to 1.85) were more common with NSAID than without. CONCLUSIONS: Adverse events were more common when allopurinol was initiated with prophylaxis, particularly diarrhoea with colchicine. Other events were uncommon, providing reassurance for patients and clinicians to enable shared decision-making.

Efficacy and safety of nelarabine in patients with relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis.

Nelarabine is approved for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients who relapse following at least two different chemotherapy regimens. Previous studies have evaluated the efficacy and safety of nelarabine with chemotherapy in the treatment of R/R T-ALL. However, the results are inconsistent. This review aimed to summarize findings on efficacy and safety data in R/R T-ALL patients administered with the drug nelarabine. The present review conducted a comprehensive search of MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until 15 January 2022. Thirteen studies fulfilled the eligibility criteria with a total of 2508 patients. The efficacy of nelarabine was studied in terms of complete remission (CR) and partial remission (PR). Included studies reported overall random-effects pooled prevalence of CR and PR were 37.2 (95% CI: 22.8, 51.5) and 10.2 (95% CI: 4.9, 15.5), respectively. Most common adverse events associated with nelarabine were neutropenia, thrombocytopenia, fatigue, infections, and reversible peripheral neuropathy. Nelarabine is being used as salvage therapy as a bridge to hematopoietic stem cell transplantation and the findings of this meta-analysis indicate that it is an effective and safe treatment to be used in addition to the first-line treatment for R/R T-ALL.

Completeness of reporting of clinical prediction models developed using supervised machine learning: a systematic review.

BACKGROUND: While many studies have consistently found incomplete reporting of regression-based prediction model studies, evidence is lacking for machine learning-based prediction model studies. We aim to systematically review the adherence of Machine Learning (ML)-based prediction model studies to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement. METHODS: We included articles reporting on development or external validation of a multivariable prediction model (either diagnostic or prognostic) developed using supervised ML for individualized predictions across all medical fields. We searched PubMed from 1 January 2018 to 31 December 2019. Data extraction was performed using the 22-item checklist for reporting of prediction model studies ( www.TRIPOD-statement.org ). We measured the overall adherence per article and per TRIPOD item. RESULTS: Our search identified 24,814 articles, of which 152 articles were included: 94 (61.8%) prognostic and 58 (38.2%) diagnostic prediction model studies. Overall, articles adhered to a median of 38.7% (IQR 31.0-46.4%) of TRIPOD items. No article fully adhered to complete reporting of the abstract and very few reported the flow of participants (3.9%, 95% CI 1.8 to 8.3), appropriate title (4.6%, 95% CI 2.2 to 9.2), blinding of predictors (4.6%, 95% CI 2.2 to 9.2), model specification (5.2%, 95% CI 2.4 to 10.8), and model's predictive performance (5.9%, 95% CI 3.1 to 10.9). There was often complete reporting of source of data (98.0%, 95% CI 94.4 to 99.3) and interpretation of the results (94.7%, 95% CI 90.0 to 97.3). CONCLUSION: Similar to prediction model studies developed using conventional regression-based techniques, the completeness of reporting is poor. Essential information to decide to use the model (i.e. model specification and its performance) is rarely reported. However, some items and sub-items of TRIPOD might be less suitable for ML-based prediction model studies and thus, TRIPOD requires extensions. Overall, there is an urgent need to improve the reporting quality and usability of research to avoid research waste. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019161764.

Factors Associated with Healing Outcomes in Primary Care Patients with Diabetic Foot Ulcers: A Retrospective Study in a Multiethnic Sample.

OBJECTIVE: To identify and determine patient- and ulcer-related factors associated with healing outcomes within 3 months for patients with diabetic foot ulcer (DFU) in a multiethnic primary care sample. METHODS: Retrospective data were collected over 3 months from 520 primary care patients with a DFU between April 1, 2016 and March 31, 2017. Multivariable prevalence ratios (PRs) were calculated using Poisson regression to find associations between patient- and ulcer-related factors and healing outcomes. RESULTS: Most patients were male (66%) and Chinese (49.8%) and had a diabetes mellitus duration longer than 5 years (81.8%). Toe ulcers (64%) were most common. Healing occurred for 33.9% of participants; 19.1% and 1.5% underwent minor and major amputation, respectively. Wound sizes between 1 and 10 cm2 (PR, 0.61; 95% confidence interval [CI], 0.46-0.76; P < .001) and over 10 cm2 (PR, 0.55; 95% CI, 0.33-0.76; P = .003), ulcer duration 6 months or longer (PR, 0.36; 95% CI, 0.19-0.53; P < .001), ischemic ulcers (PR, 0.54; 95% CI, 0.22-0.86; P = .044), and neuroischemic ulcers (PR, 0.73; 95% CI, 0.53-0.93; P = .027) were negatively associated with healing outcomes. Women were more likely to experience healing (PR, 1.18; 95% CI, 0.91-1.45; P = .157). CONCLUSIONS: Ulcer healing varied by sex and was affected by wound size, wound duration, and ischemic etiology, regardless of ethnicity. Prompt attention to these risk factors may reduce healing time. Further studies are warranted to elucidate the mechanism underlying sex differences in association with DFU healing.

Health-related quality of life and chronic wound characteristics among patients with chronic wounds treated in primary care: A cross-sectional study in Singapore.

Chronic wounds commonly decrease patients' quality of life. Understanding how chronic wounds impact a patient's health-related quality of life (HRQoL) is important for healthcare service delivery and treatment management. This study explored HRQoL among patients suffering from chronic wounds and investigated associations with patients' socio-demographics and wound characteristics. Two hundred and thirty-three patients across six primary care clinics were assessed and responded to a survey that collected information on socio-demographic, wound characteristics, and HRQoL using the EQ-5D-5L instrument. Data were analysed by descriptive statistics and generalised linear models. The mean age of patients was 61.2 (SD: 14.6) years; 68.2% were males; and 61.8% were of Chinese origin. Arterial ulcers had the greatest negative impact on HRQoL related to mobility, self-care, pain/discomfort and anxiety/depression, and the lowest VAS mean score 62.31 (SD: 28.3; range: 0-100) indicating the worst health. HRQoL related to mobility was significantly associated with age (ß = 0.008, P < .001), non-Chinese ethnicity (ß = 0.25, P = .001), mixed ulcers (ß = -0.41, P = .022), atypical hard-to-heal wounds (ß = -0.38, P = .021), wounds with low (ß = 0.24, P = .044) to moderate (ß = 0.29, P = .018) exudate level, and a wound duration ≥6 months (ß = 0.19, P = .033). The findings can be used to improve healthcare delivery for patients with chronic wound to optimise their HRQoL.

Onset of comorbidities and flare patterns within pre-existing morbidity clusters in people with gout: 5-year primary care cohort study.

OBJECTIVE: To investigate the onset of comorbidities and pattern of flares over 5 years according to baseline comorbidity clusters in people with gout. METHODS: In a prospective primary care-based cohort study, adults aged ≥18 years with gout were identified from primary care medical records in 20 general practices across the West Midlands, UK and followed up over 5 years. Four clusters of participants have been defined previously according to baseline comorbidity status. The associations of (i) incident comorbidities and (ii) gout flares with baseline cluster membership were estimated using age and sex-adjusted Poisson regression and mixed effects ordinal logistic regression, respectively. RESULTS: The comorbidity with the highest incidence was coronary artery disease (39.2%), followed by hypertension (36.7%), chronic kidney disease stage ≥3 (18.1%), obesity (16.0%), hyperlipidaemia (11.7%), diabetes (8.8%) and cancer (8.4%). There were statistically significant associations observed between cluster membership and incidence of coronary artery disease, hyperlipidaemia, heart failure and hypertension. In each cluster, nearly one-third of participants reported two or more gout flares at each time-point. History of oligo/polyarticular flares (odds ratio [OR]= 2.16, 95% confidence interval [CI]: 1.73, 2.70) and obesity (1.66, 95% CI: 1.21, 2.25) were associated with increasing flares whereas current use of allopurinol was associated with lower risk (0.42, 95% CI: 0.34-0.53). Cluster membership was not associated with flares. CONCLUSION: Substantial numbers of people in each cluster developed new comorbidities that varies by cluster membership. People also experienced multiple flares over time, but these did not differ between clusters. Clinicians should be vigilant for the development of new comorbidities in people with gout.

Visual recovery after small incision lenticule extraction (SMILE) in relation to pre-operative spherical equivalent.

PURPOSE: To assess visual recovery after small incision lenticule extraction (SMILE) in relation to pre-operative spherical equivalent. METHODS: Two hundred fourteen eyes of 107 patients were enrolled. Following surgery, patients were examined pre-operatively, 1 day, 2 weeks, 1 month and 3 months later. High myopia was defined as pre-operative spherical equivalent ≤ - 5 D. A linear mixed-effects model was used. RESULTS: Mean ± standard deviation pre-operative spherical equivalent was - 5.30 ± 1.36 D that reduced significantly to 0.04 ± 0.70 D (p < 0.001) at 1 month and - 0.02 ± 0.66 D (p < 0.001) at 3 months. Mean pre-operative LogMAR uncorrected distance visual acuity ± SD was 0.97 ± 0.09 that improved significantly to 0.04 ± 0.06 at 2 weeks (p < 0.001), 0.01 ± 0.04 at 1 month (p < 0.001) and 0.01 ± 0.04 at 3 months (p < 0.001). Eighty-eight eyes (41.2%) had uncorrected distance visual acuities of 0.0 at 1 day, 154 eyes (72.0%) at 2 weeks,194 eyes (90.7%) at 1 month and 199 eyes (93.0%) at 3 months. Significantly more eyes with low myopia (> - 5 D) achieved acuities of 0.0 at 1 day and 2 weeks (p = 0.041 and p < 0.001). Post-operative acuities were not associated with refractive targets, laser cut energy settings or other variables. Two hundred nine eyes (97.7%) were within ± 0.5 D of target and 213 eyes (99.5%) were within ± 1 D. CONCLUSIONS: SMILE for low myopia had faster visual recovery in the early post-operative period with no significant differences between groups detected by 1 and 3 months.

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis.

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease. METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. CONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients.

Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis.

PURPOSE: In the past few years, several fracture-related events have been reported with chronic use of selective serotonin reuptake inhibitors (SSRIs) throughout the globe. Hence, an updated systematic review and meta-analysis was necessary to ascertain the risk involved. The present work evaluated the association of SSRIs with the risk of fracture in adults. METHODS: We systematically searched PubMed, Cochrane library, and Google Scholar for observational studies on the same from inception to April 2019. Screening, data extraction, and risk of bias assessment were conducted independently by 2 authors. RESULTS: We assessed 69 studies out of which 37 (14 case-control, 23 cohorts) were included. Our results showed that SSRIs were significantly associated with an increased fracture risk (relative risk of 1.62, 95% CI 1.52-1.73; P < 0.000; I2 = 90.8%). The relative risk values for case-control and cohort studies were found to be 1.80 (95% CI 1.58-2.03; P < 0.000; I2 = 93.2%) and 1.51 (95% CI 1.39-1.64; P < 0.000; I2 = 88.0%) respectively. Subgroup analysis showed that association of risk of fracture persisted regardless of geographical location, study design, risk factors, defined daily dose, SSRI use duration, site of the fracture, period of study and after adjusting for depression, physical activity, gender, and age group. The sensitivity analysis data shows that the studies adjusted for bone mineral density and osteoporosis show lesser fracture risk. CONCLUSION: Our findings suggests that SSRIs may be associated with an increased fracture risk; hence, bone health should be taken into consideration while prescribing this class of drugs.

Concordance Between Physician-rated and Caregiver-perceived Disease Severity in Children with Atopic Dermatitis: A Cross-sectional Study.

This study examined concordance between caregiver-reported and physician-rated estimates of severity of atopic dermatitis (AD) in paediatric patients and explored potential explanatory factors. Physician-reported severity of AD was retrieved from medical records, while caregiver-reported disease severity and sociodemographic data were obtained through a survey that also collected information on out-of-pocket expenses due to AD. There was 38.5% (95% confidence interval (95% CI) 30.1, 43.5) disagreement between physician and caregivers with regards to both underestimating and overestimating the condition. A duration since AD diagnosis shorter than 6 months showed higher concordance (kappa: 44.4%; 95% CI 30.6, 58.2) between caregiver and physician estimates of AD severity compared with a duration of 6 months or longer. Caregivers underestimating their child's AD accounted for 27.7% among all participants, while 10.8% overestimated the severity of AD compared with physicians. Factors significantly associated with caregiver's underestimation of disease severity were age of the child and time since disease diagnosis. Comparison of concordance between caregiver-reported and physician-rated estimates of severity of AD in paediatric patients revealed a tendency amongst caregivers to underestimate severity of AD. This information may have clinical implications for treatment outcomes if caregivers fail to adhere to medical advice.

Small incision lenticule extraction (SMILE) lenticule thickness readout compared to change in axial length measurements with the IOLMaster.

PURPOSE: To compare theoretical values from the small incision lenticule extraction (SMILE) lenticule thickness readout with change in axial length measurements taken with the IOLMaster. METHODS: We prospectively studied 214 eyes from 107 patients undergoing bilateral SMILE surgery for myopia or myopic astigmatism between December 2014 and May 2017 at an ophthalmological practice in Singapore. All eyes were examined pre-operatively and 1 and 3 months post-operatively with the IOLMaster following SMILE surgery. Achieved lenticule thickness was taken as the change in axial length after surgery. A linear mixed-effects model was used to examine changes in axial length, spherical equivalent and acuity over time. The relationships between change in axial length and theoretical lenticule thickness and spherical equivalent were examined with multiple linear regression analyses, and model prediction was assessed with adjusted R2 statistics. RESULTS: Mean (95% confidence interval [CI]) spherical equivalent pre-operatively was - 5.25 (95% CI - 5.38 to - 5.12) diopters (D), at 1 month was 0.04 (95% CI - 0.09 to 0.17) D (p < 0.001), and at 3 months was - 0.02 (95% CI - 0.15 to 0.11) D (p < 0.001). Mean (95% CI) pre-operative axial length was 27,726 (95% CI 25,595 to 25,857) µm. Post-operative axial length at 1 month was significantly shorter at 25,595 (95% CI 25,464 to 25,726) µm (p < 0.001) with no change thereafter (p = 0.647). Pre-operative mean ± standard deviation (SD) refractive target was 0.24 (± 0.3) D, and mean difference between target and post-operative spherical equivalent at 1 month was 0.20 D (95% CI 0.16 to 0.25 D, p < 0.001). Multiple regression analysis showed that change in axial length at 1 month was, on average, 5% lower than theoretical lenticule thickness, indicating an average difference of 5.4 µm (95% CI 5.2 to 5.6 µm). Preoperative spherical equivalent predicted negative association with change in axial length at 1 month (ß = - 14.8, 95% CI - 18.2 to - 11.3, adjusted R2 = 0.457, p < 0.001). CONCLUSIONS: Calculated lenticule thickness values were less than expected, and post-operative refractive outcomes at 1 month showed a slight under-correction. Further research in this area is needed to validate these findings.

Determination of cut-off and correlates of delay in treatment-seeking of febrile illness: a retrospective analysis.

BACKGROUND: Early diagnosis and treatment of malaria symptoms reduces the risk of severe complication and malaria transmission. However, delay in malaria diagnosis and treatment is a major public health problem in India. The primary aim of the study was to determine cut-off for the delay in seeking treatment of fever, and the secondary aim was to identify the factors associated with delay in malaria-endemic areas of Assam, Northeast India. METHODS: The present study analysed data from two prior cross-sectional surveys (community- and hospital-based) that was conducted to study the health-seeking behaviour of people residing in high malaria-endemic areas of Assam, Northeast India. The hospital-based survey data were used to determine optimal cut-off for the delay in reporting, and further, used to identify the factors associated with delay using community-based data. RESULTS: Mean age of fever cases was similar in both community- and hospital-based surveys (23.1 years vs 24.2 years, p = 0.229). Delay in reporting fever was significantly higher among hospital inpatients compared to community-based fever cases (3.6 ± 2.1 vs 4.0 ± 2.6 days; p = 0.006). Delay of > 2 days showed higher predictive ability (sensitivity: 96.4%, and ROC area: 67.5%) compared to other cut-off values (> 3, > 4, and > 5 days). Multivariable logistic regression analysis revealed that the adjusted odds ratio (aOR) of delay was significantly higher for people living in rural areas (1.52, 95%CI: 1.11-2.09), distance (> 5 km) to health facility (1.93, 95%CI: 1.44-2.61), engaged in agriculture work (2.58, 95%CI: 1.97-3.37), and interaction effect of adult male aged 20-40 years (1.71, 95%CI: 1.06-2.75). CONCLUSION: The delay (> 2 days) in seeking treatment was likely to be twice among those who live in rural areas and travel > 5 km to assess health care facility. The findings of the study are useful in designing effective intervention programmes for early treatment of febrile illness to control malaria.

Exercise/physical activity and health outcomes: an overview of Cochrane systematic reviews.

BACKGROUND: Sedentary lifestyle is a major risk factor for noncommunicable diseases such as cardiovascular diseases, cancer and diabetes. It has been estimated that approximately 3.2 million deaths each year are attributable to insufficient levels of physical activity. We evaluated the available evidence from Cochrane systematic reviews (CSRs) on the effectiveness of exercise/physical activity for various health outcomes. METHODS: Overview and meta-analysis. The Cochrane Library was searched from 01.01.2000 to issue 1, 2019. No language restrictions were imposed. Only CSRs of randomised controlled trials (RCTs) were included. Both healthy individuals, those at risk of a disease, and medically compromised patients of any age and gender were eligible. We evaluated any type of exercise or physical activity interventions; against any types of controls; and measuring any type of health-related outcome measures. The AMSTAR-2 tool for assessing the methodological quality of the included studies was utilised. RESULTS: Hundred and fifty CSRs met the inclusion criteria. There were 54 different conditions. Majority of CSRs were of high methodological quality. Hundred and thirty CSRs employed meta-analytic techniques and 20 did not. Limitations for studies were the most common reasons for downgrading the quality of the evidence. Based on 10 CSRs and 187 RCTs with 27,671 participants, there was a 13% reduction in mortality rates risk ratio (RR) 0.87 [95% confidence intervals (CI) 0.78 to 0.96]; I2 = 26.6%, [prediction interval (PI) 0.70, 1.07], median effect size (MES) = 0.93 [interquartile range (IQR) 0.81, 1.00]. Data from 15 CSRs and 408 RCTs with 32,984 participants showed a small improvement in quality of life (QOL) standardised mean difference (SMD) 0.18 [95% CI 0.08, 0.28]; I2 = 74.3%; PI -0.18, 0.53], MES = 0.20 [IQR 0.07, 0.39]. Subgroup analyses by the type of condition showed that the magnitude of effect size was the largest among patients with mental health conditions. CONCLUSION: There is a plethora of CSRs evaluating the effectiveness of physical activity/exercise. The evidence suggests that physical activity/exercise reduces mortality rates and improves QOL with minimal or no safety concerns. TRIAL REGISTRATION: Registered in PROSPERO ( CRD42019120295 ) on 10th January 2019.

Associations between health-related quality of life and health care costs among children with atopic dermatitis and their caregivers: A cross-sectional study.

BACKGROUND/OBJECTIVES: Atopic dermatitis is associated with a decreased health-related quality of life and contributes to substantial health care costs. It is important to understand what accelerates health care costs to inform various stakeholders, so they can effectively meet health care needs. This cross-sectional study aims to explore associations between health-related quality of life, health care costs, and cost-accelerating variables. METHODS: Information on health-related quality of life (HRQoL) was collected through generic and disease-specific instruments from caregivers and children <16 years of age with a physician-confirmed diagnosis of atopic dermatitis. The economic impact of atopic dermatitis was evaluated by analyzing information on health service utilization and other health care costs related to managing the condition. RESULTS: Children with high impact on health-related quality of life presented an annual health care cost of US$ 3787 compared with US$ 2548 for moderately impacted and US$ 2258 among children for which the condition had low impact. The severity of atopic dermatitis, disease duration, and a lower health-related quality of life was associated with greater health care costs. Analyses of subdomains of health-related quality of life revealed correlations between "mood" and "personal relationships" on one hand and caregivers' physical health and health care costs on the other hand. CONCLUSIONS: Highly affected HRQoL is associated with increased health care costs and could be a valuable complement to traditional severity assessments. By using HRQoL instruments, burdens and symptoms beyond severity can be identified and addressed with interventions to increase HRQoL and subsequently reduce health care costs.

The humanistic and economic burden of chronic wounds: A systematic review.

Chronic wounds are a health problem that have devastating consequences for patients and contribute major costs to healthcare systems and societies. To understand the magnitude of this health issue, a systematic review was undertaken. Searches were conducted in MEDLINE, EMBASE, EBM Reviews and Cochrane library, CINAHL, EBSCO, PsycINFO, and Global Health databases for articles published between 2000 and 2015. Included publications had to target adults (≥18 years of age), state wound chronicity (≥3 weeks) and/or label the wounds as chronic, complex, hard-to-heal, or having led to an amputation. The review excluded studies that did not present data on generic health-related quality of life and/or cost data, case studies, randomized controlled trials, economic modeling studies, abstracts, and editorials. Extracted data were summarized into a narrative synthesis, and for a few articles using the same health-related quality of life instrument, average estimates with 95% confidence intervals were calculated. Thirty articles met the inclusion criteria. Findings revealed that health-related quality of life was lowest for physical pathologies, and based on average estimates were scores most inferior in the domain physical role for both patients with chronic wounds and for those with wound-related amputations. The cost burden was mainly attributed to amputations for patients also comorbid with diabetes, where the cost for hospitalization ranged from US$12,851 to US$16,267 (median) for this patient group. Patients with chronic wounds have poor health-related quality of life in general and wound-related costs are substantial. Development and implementation of wound management strategies that focus on increasing health-related quality of life and effectively reduce costs for this patient group are urgently needed.

Health Professions' Digital Education: Review of Learning Theories in Randomized Controlled Trials by the Digital Health Education Collaboration.

BACKGROUND: Learning theory is an essential component for designing an effective educational curriculum. Reviews of existing literature consistently lack sufficient evidence to support the effectiveness of digital interventions for health professions' education, which may reflect disconnections among learning theories, curriculum design, use of technology, and outcome evaluation. OBJECTIVE: The aim of this review was to identify, map, and evaluate the use of learning theories in designing and implementing intervention trials of health professions' digital education, as well as highlight areas for future research on technology-enhanced education via the establishment of a development framework for practice and research. METHODS: We performed a systematic search of Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cochrane Central Register of Controlled Trials (Cochrane Library), PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Education Resources Information Center, and Web of Science for randomized controlled trials (RCTs) published between 2007 and 2016. RESULTS: A total of 874 RCTs on digital health education were identified and categorized into online-offline, mobile digital education, and simulation-based modalities for pre and postregistration health professions' education. Of these, 242 studies were randomly selected for methodological review and thematic analysis. Data were extracted by one author using a standardized form, with a (48/242, 20%) random sample extracted by a second author, in duplicate. One-third (81/242, 33.4%) of the studies reported single or multiple learning theories in design, assessment, conceptualization, or interpretation of outcomes of the digital education interventions. Commonly reported learning theories were problem-based learning (16/81, 20%), social learning theory (11/81, 14%), and cognitive theory of multimedia learning (10/81, 12%). Most of these studies assessed knowledge (118/242, 48.8%), skills (62/242, 25.6%), and performance (59/242, 24.3%) as primary outcomes with nonvalidated assessment tools (151/242, 62.4%). Studies with reported learning theories (χ21=8.2; P=.002) and validated instruments (χ21=12.6; P=.006) have shown effective acquisition of learning outcomes. CONCLUSIONS: We proposed a Theory-Technology Alignment Framework to safeguard the robustness and integrity of the design and implementation of future digital education programs for the training of health professionals.

Digital Education for Health Professions on Smoking Cessation Management: Systematic Review by the Digital Health Education Collaboration.

BACKGROUND: Tobacco smoking, one of the leading causes of preventable death and disease, is associated with 7 million deaths every year. This is estimated to rise to more than 8 million deaths per year by 2030, with 80% occurring in low- and middle-income countries. Digital education, teaching, and learning using digital technologies have the potential to increase educational opportunities, supplement teaching activities, and decrease distance barriers in health professions education. OBJECTIVE: The primary objective of this systematic review was to evaluate the effectiveness of digital education compared with various controls in improving learners' knowledge, skills, attitudes, and satisfaction to deliver smoking cessation therapy. The secondary objectives were to assess patient-related outcomes, change in health professionals' practice or behavior, self-efficacy or self-rated competence of health professionals in delivering smoking cessation therapy, and cost-effectiveness of the interventions. METHODS: We searched 7 electronic databases and 2 trial registers for randomized controlled trials published between January 1990 and August 2017. We used gold standard Cochrane methods to select and extract data and appraise eligible studies. RESULTS: A total of 11 studies (number of participants, n=2684) were included in the review. All studies found that digital education was at least as effective as traditional or usual learning. There was some suggestion that blended education results in similar or greater improvements in knowledge (standardized mean difference, SMD=0.19, 95% CI -0.35 to 0.72), skill (SMD=0.58, 95% CI 0.08-1.08), and satisfaction (SMD=0.62, 95% CI 0.12-1.12) compared with digital education or usual learning alone. There was also some evidence for improved attitude (SMD=0.45, 95% CI 0.18-0.72) following digital education compared with usual learning. Only 1 study reported patient outcomes and the setup cost of blended education but did not compare outcomes among groups. There were insufficient data to investigate what components of the digital education interventions were associated with the greatest improvements in learning outcomes. CONCLUSIONS: The evidence suggests that digital education is at least as effective as usual learning in improving health professionals' knowledge and skill for delivering smoking cessation therapy. However, limitations in the evidence base mean that these conclusions should be interpreted with some caution. TRIAL REGISTRATION: PROSPERO CRD42016046815; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=46815.