METHODS: This was a randomized controlled parallel-group trial in which 372 antenatal care attendees were randomly assigned to either an intervention or control group after collecting baseline data using a structured questionnaire. The intervention group received a 4-h health education on malaria, guided by a module developed based on the IMB theory, while the control group received health education on breastfeeding for a similar duration and by the same facilitator. Follow-up data were subsequently collected at 2 months and at 4 months post-intervention using the same questionnaire. The generalized linear mixed models analysis was used to determine the between-group and within-group effects of the intervention. The intention-to-treat analysis was used after missing data had been replaced. This was followed by a sensitivity analysis, where the analyses were repeated without replacing the missing values.
RESULTS: The intervention was significant in achieving a 12.75% (p
METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years.
FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI.
INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments.
FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.
METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.
RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.
CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.
METHODS: This was a post-hoc analysis from the all-comers EASTBOURNE Registry (NCT03085823). Out of 2083 patients enrolled, an SCB was used to treat 968 (46.5%) ACS and 1115 (53.5%) CCS patients. The primary endpoint was target lesion revascularization at 12 months, while secondary endpoints were angiographic success and major adverse cardiovascular events.
RESULTS: Baseline demographics, mean reference vessel diameter and mean lesion length were comparable between ACS and CCS. Predilatation was more commonly performed in ACS (P=.007). SCB was inflated at a standard pressure in both groups with a slight trend toward longer inflation time in ACS. Angiographic success was high in both groups (ACS 97.4% vs CCS 97.7%, P=.820) with limited bailout stenting. Similarly, at 12 months the cumulative incidence of target lesion revascularization (ACS 6.6% vs CCS 5.2%, P=.258) was comparable between ACS and CCS. Conversely, a higher rate of major adverse cardiovascular events in acute presenters was mainly driven by myocardial infarction recurrencies (ACS 10.4% vs CCS 8.3%, P=.009). In-stent restenosis showed a higher proportion of target lesion revascularization and major adverse cardiovascular events than de novo lesions, independently of the type of presentation at the index procedure.
CONCLUSIONS: This SCB shows good performance in terms of acute and 1-year outcomes independently of the clinical presentation.
METHODS: We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.
RESULTS: All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.
CONCLUSIONS: Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women.
OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.
SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .
SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes. We evaluated the overall quality of the evidence supporting the outcomes assessed in this review using the GRADE criteria.
MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.We are very uncertain about the effects of TES on bowel movements, colonic transit, soiling symptoms and quality of life due to high risk of bias, indirectness and imprecision. For our outcomes of interest the 95% CI of most analysis results include potential benefit and no effect. There is insufficient evidence to determine the effect of TES on bowel movements and colonic transit. The study reported that 16/21 children in the TES group and 15/21 in the sham group had > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53; very low-quality evidence). Ten out of 14 children in the TES group had improved colonic transit compared to 1/7 in the sham group (RR 5.00, 95% CI 0.79 to 31.63; very low-quality evidence). Mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants; very low-quality evidence). The radiological assessment of colonic transit outcomes means that these results might not translate to important improvement in clinical symptoms or increased bowel movements. There is insufficient evidence to determine the effect of TES on symptoms and quality of life (QoL) outcomes. Nine out of 13 children in the TES group had improved soiling-related symptoms compared to 4/12 sham participants (RR 2.08, 95% CI 0.86 to 5.00; very low-quality evidence). Four out of 8 TES participants reported an improvement in QoL compared to 1/8 sham participants (RR 4.00, 95% CI 0.56 to 28.40; very low-quality evidence). The effects of TES on self-perceived (MD 5.00, 95% CI -1.21 to 11.21; one study, 33 participants; very low-quality evidence) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants; very low-quality evidence) are uncertain. No adverse effects were reported in the included study.
AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.
METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.
RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).
CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.
METHODS: An outbreak was declared following the detection of P. malariae in July 2020 and active case detection for malaria was performed by collecting blood samples from residents residing within 2 km radius of Moyog village. Vector prevalence and the efficacy of residual insecticides were determined. Health awareness programmes were implemented to prevent future outbreaks. A survey was conducted among villagers to understand risk behaviour and beliefs concerning malaria.
RESULTS: A total of 5254 blood samples collected from 19 villages. Among them, 19 P. malariae cases were identified, including the index case, which originated from a man who returned from Indonesia. His return from Indonesia and healthcare facilities visit coincided with the movement control order during COVID-19 pandemic when the healthcare facilities stretched its capacity and only serious cases were given priority. Despite the index case being a returnee from a malaria endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. All cases were symptomatic and uncomplicated except for a pregnant woman with severe malaria. There were no deaths; all patients recovered following treatment with artemether-lumefantrine combination therapy. Anopheles balabacensis and Anopheles barbirostris were detected in ponds, puddles and riverbeds. The survey revealed that fishing and hunting during night, and self-treatment for mild symptoms contributed to the outbreak. Despite the index case being a returnee from a malaria-endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities.
CONCLUSION: The outbreak occurred during a COVID-19 movement control order, which strained healthcare facilities, prioritizing only serious cases. Healthcare workers need to be more aware of the risk of malaria from individuals who return from malaria endemic areas. To achieve malaria elimination and prevention of disease reintroduction, new strategies that include multisectoral agencies and active community participation are essential for a more sustainable malaria control programme.
METHODS: A retrospective analysis was conducted using national administrative data from 1124 public primary care clinics. Eight indicators were selected to measure service utilisation covering antenatal, postnatal, women's health, child health, and immunisation services. Interrupted time-series analysis was used to evaluate changes in levels and trends of indicators during four different periods: pre-pandemic (January 2019-February 2020), during pandemic and first lockdown (March-May 2020), after the first lockdown was lifted (June-December 2020) and after the second lockdown was implemented (January-June 2021).
RESULTS: Most indicators showed no significant trend in monthly utilisation prior to the pandemic. The onset of the pandemic and first lockdown implementation were associated with significant decreasing trends in child health (-19.23%), women's health (-10.12%), antenatal care (-8.10%), contraception (-6.50%), postnatal care (-4.85%) and postnatal care 1-week (-3.52%) indicators. These indicators showed varying degrees of recovery after the first lockdown was lifted. The implementation of the second lockdown caused transient reduction ranging from -11.29% to -25.92% in women's health, contraception, child and two postnatal indicators, but no sustained reducing trend was seen afterwards. Two immunisation indicators appeared unaffected throughout the study period.
CONCLUSION: The COVID-19 pandemic significantly impacted MCH services utilisation in Malaysia. While most MCH services were negatively affected by the lockdown implementation with varying degrees of recovery, infant immunisation showed resilience throughout. This highlights the need for a targeted preparedness plan to ensure the resilience of MCH services in future crises.
OBJECTIVES: To assess the effects of magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease in adults.
SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) trials portal, EU Clinical Trials Register and Iranian Registry of Clinical Trials. We also searched the proceedings of major respiratory conferences and reference lists of included studies up to 2 August 2021.
SELECTION CRITERIA: We included single- or double-blind parallel-group randomised controlled trials (RCTs) assessing magnesium sulfate in adults with COPD exacerbations. We excluded cross-over trials.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. The primary outcomes were: hospital admissions (from the emergency room); need for non-invasive ventilation (NIV), assisted ventilation or admission to intensive-care unit (ICU); and serious adverse events. Secondary outcomes were: length of hospital stay, mortality, adverse events, dyspnoea score, lung function and blood gas measurements. We assessed confidence in the evidence using GRADE methodology. For missing data, we contacted the study investigators.
MAIN RESULTS: We identified 11 RCTs (10 double-blind and 1 single-blind) with a total 762 participants. The mean age of participants ranged from 62 to 76 years. Trials were single- or two-centre trials conducted in Iran, New Zealand, Nepal, Turkey, the UK, Tunisia and the USA between 2004 and 2018. We judged studies to be at low or unclear risk of bias for most of the domains. Three studies were at high risk for blinding and other biases. Intravenous magnesium sulfate versus placebo Seven studies (24 to 77 participants) were included. Fewer people may require hospital admission with magnesium infusion compared to placebo (odds ratio (OR) 0.45, 95% CI 0.23 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) = 7; 3 studies, 170 participants; low-certainty evidence). Intravenous magnesium may result in little to no difference in the requirement for non-invasive ventilation (OR 0.74, 95% CI 0.31 to 1.75; very low-certainty evidence). There were no reported cases of endotracheal intubation (2 studies, 107 participants) or serious adverse events (1 study, 77 participants) in either group. Included studies did not report intensive care unit (ICU) admission or deaths. Magnesium infusion may reduce the length of hospital stay by a mean difference (MD) of 2.7 days (95% CI 4.73 days to 0.66 days; 2 studies, 54 participants; low-certainty evidence) and improve dyspnoea score by a standardised mean difference of -1.40 (95% CI -1.83 to -0.96; 2 studies, 101 participants; low-certainty evidence). We were uncertain about the effect of magnesium infusion on improving lung function or oxygen saturation. For all adverse events, the Peto OR was 0.14 (95% CI 0.02 to 1.00; 102 participants); however, the event rate was too low to reach a robust conclusion. Nebulised magnesium sulfate versus placebo Three studies (20 to 172 participants) were included. Magnesium inhalation may have little to no impact on hospital admission (OR 0.77, 95% CI 0.21 to 2.82; very low-certainty evidence) or need for ventilatory support (NIV or mechanical ventilation) (OR 0.33, 95% CI 0.01 to 8.20; very low-certainty evidence). It may result in fewer ICU admissions compared to placebo (OR 0.39, 95% CI 0.15 to 1.00; very low-certainty evidence) and improvement in dyspnoea (MD -14.37, 95% CI -26.00 to -2.74; 1 study, 20 participants; very low-certainty evidence). There were no serious adverse events reported in either group. There was one reported death in the placebo arm in one trial, but the number of participants was too small for a conclusion. There was limited evidence about the effect of magnesium inhalation on length of hospital stay, lung function outcomes or oxygen saturation. Included studies did not report adverse events. Magnesium sulfate versus ipratropium bromide A single study with 124 participants assessed nebulised magnesium sulfate plus intravenous magnesium infusion versus nebulised ipratropium plus intravenous normal saline. There was little to no difference between these groups in terms of hospital admission (OR 1.62, 95% CI 0.78 to 3.37), endotracheal intubation (OR 1.69, 95% CI 0.61 to 4.71) and length of hospital stay (MD 1.10 days, 95% CI -0.22 to 2.42), all with very low-certainty evidence. There were no data available for non-invasive ventilation, ICU admission and serious adverse events. Adverse events were not reported. AUTHORS' CONCLUSIONS: Intravenous magnesium sulfate may be associated with fewer hospital admissions, reduced length of hospital stay and improved dyspnoea scores compared to placebo. There is no evidence of a difference between magnesium infusion and placebo for NIV, lung function, oxygen saturation or adverse events. We found no evidence for ICU admission, endotracheal intubation, serious adverse events or mortality. For nebulised magnesium sulfate, we are unable to draw conclusions about its effects in COPD exacerbations for most of the outcomes. Studies reported possibly lower ICU admissions and a lesser degree of dyspnoea with magnesium inhalation compared to placebo; however, larger studies are required to yield a more precise estimate for these outcomes. Similarly, we could not identify any robust evidence for magnesium sulfate compared to ipratropium bromide. Future well-designed multicentre trials with larger samples are required, including subgroups according to severity of exacerbations and COPD phenotypes.
METHODS: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.
RESULTS: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.
CONCLUSIONS: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).
AREAS COVERED: Herein, the authors discuss the various factors that contribute to the quality of studies using animal models based on the evaluation of studies published in 2022. The factors affecting the quality of studies using animal models, such as the animal species, age, and sex, are discussed, along with various methods and outcomes of studies involving different animal models of glaucoma.
EXPERT OPINION: Translating animal research data to clinical applications remains challenging. Our observations in this review clearly indicate that many studies lack scientific robustness not only in their experiment conduct but also in data analysis, interpretation, and presentation. In this context, ensuring the internal validity of animal studies is the first step in quality assurance. External validity, however, is more challenging, and steps should be taken to satisfy external validity at least to some extent.