The impact of home-based management of malaria on clinical outcomes in sub-Saharan African populations: a systematic review and meta-analysis.

BACKGROUND: Malaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the effect of home management of malaria intervention on health outcomes. METHODS: In our systematic review and meta-analysis, six databases (Pubmed, Cochrane CENTRAL, EMBASE, CAB Abstracts and Global Health, CINAHL Complete, and BIOSIS) were searched for studies of home management of malaria from inception until November 15, 2023. We included before-after studies, observational studies, and randomised controlled trials of home management intervention delivered in community settings. The primary outcomes were malaria mortality and all-cause mortality. The risk of bias in individual observational studies was assessed using the ROBINS-I tool, whilst randomised controlled trials were judged using a revised Cochrane risk of bias tool and cluster-randomised controlled trials were evaluated using an adapted Cochrane risk of bias tool for cluster-randomised trials. We computed risk ratios with accompanying 95% confidence intervals for health-related outcomes reported in the studies and subsequently pooled the results by using a random-effects model (DerSimonian-Laird method). RESULTS: We identified 1203 citations through database and hand searches, from which 56 articles from 47 studies encompassing 234,002 participants were included in the systematic review. All studies were conducted in people living in sub-Saharan Africa and were rated to have a low or moderate risk of bias. Pooled analyses showed that mortality rates due to malaria (RR = 0.40, 95% CI = 0.29-0.54, P = 0.00001, I2 = 0%) and all-cause mortality rates (RR = 0.62, 95% CI = 0.53-0.72, P = 0.00001, I2 = 0%) were significantly lower among participants receiving home management intervention compared to the control group. However, in children under 5 years of age, there was no significant difference in mortality rates before and after implementation of home management of malaria. In terms of secondary outcomes, home management of malaria was associated with a reduction in the risk of febrile episodes (RR = 1.27, 95% CI = 1.09-1.47, P = 0.002, I2 = 97%) and higher effective rates of antimalarial treatments (RR = 2.72, 95% CI = 1.90-3.88, P < 0.00001, I2 = 96%) compared to standard care. Home malaria management combined with intermittent preventive treatment showed a significantly lower incidence risk of malaria than home management intervention that exclusively provided treatment to individuals with febrile illness suggestive of malaria. The risks for adverse events were found to be similar for home management intervention using different antimalarial drugs. Cost-effectiveness findings depicted that home malaria management merited special preferential scale-up. CONCLUSIONS: Home management of malaria intervention was associated with significant reductions in malaria mortality and all-cause mortality. The intervention could help decrease health and economic burden attributable to malaria. Further clinical studies are warranted to enable more meaningful interpretations with regard to wide-scale implementation of the intervention, settings of differing transmission intensity, and new antimalarial drugs.

SARS-CoV-2 neutralizing antibody bebtelovimab - a systematic scoping review and meta-analysis.

Introduction: The COVID-19 pandemic is a major global public health crisis. More than 2 years into the pandemic, effective therapeutic options remain limited due to rapid viral evolution. Stemming from the emergence of multiple variants, several monoclonal antibodies are no longer suitable for clinical use. This scoping review aimed to summarize the preclinical and clinical evidence for bebtelovimab in treating newly emerging SARS-CoV-2 variants. Methods: We systematically searched five electronic databases (PubMed, CENTRAL, Embase, Global Health, and PsycINFO) from date of inception to September 30, 2022, for studies reporting on the effect of bebtelovimab in SARS-CoV-2 infection, using a combination of search terms around -bebtelovimab‖, -LY-CoV1404‖, -LY3853113‖, and -coronavirus infection‖. All citations were screened independently by two researchers. Data were extracted and thematically analyzed based on study design by adhering to the stipulated scoping review approaches. Results: Thirty-nine studies were included, thirty-four non-clinical studies were narratively synthesized, and five clinical studies were meta-analyzed. The non-clinical studies revealed bebtelovimab not only potently neutralized wide-type SARS-CoV-2 and existing variants of concern such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but also retained appreciable activity against Omicron lineages, including BA.2.75, BA.4, BA.4.6, and BA.5. Unlike other monoclonal antibodies, bebtelovimab was able to bind to epitope of the SARS-CoV-2 S protein by exploiting loop mobility or by minimizing side-chain interactions. Pooled analysis from clinical studies depicted that the rates of hospitalization, ICU admission, and death were similar between bebtelovimab and other COVID-19 therapies. Bebtelovimab was associated with a low incidence of treatment-emergent adverse events. Conclusion: Preclinical evidence suggests bebtelovimab be a potential treatment for COVID-19 amidst viral evolution. Bebtelovimab has comparable efficacy to other COVID-19 therapies without evident safety concerns.

Better health through better housing - Current impact and future prospects of randomized trials.

Safe and stable housing in integrated neighborhoods with access to basic amenities and social elements is indispensable for good health. Recent randomized controlled trials have demonstrated that improvements in the built environment have positive impacts on malaria, fall injuries, and gun violence outcomes. There are several challenges associated with performing studies that assess house improvement as an intervention for advancing human health and well-being, including ethical issues, lack of blinding, spillover effects, and differential behavior. Future research is warranted to evaluate the clinical benefits and cost-effectiveness of prototype houses or energy-efficient prefabricated modular homes by employing more holistic strategies, such as integration of data analytics, peer support, and whole health coaching, addition of social contextual perspectives on mobile technology-supported community-based interventions, and combination of digital technology-informed community-engaged citizen science and participatory action programs with multisector partnerships. Gleaning stronger evidence from clinical trials and model-based economic analyses that ascertain the effects of multiple intersecting factors on individuals and communities would illuminate effective policy making options in healthy housing and guide successful implementation of sustainable public health policies. Straightforward and cost-effective pathways should therefore be created based on highest-quality scientific data to lead the scaling up of novel housing interventions and capacity building for health-in-all-policies to support population health equity, thereby ensuring that everyone has access to housing and the chance to live a healthy and productive life.

Association Between Cytomegalovirus Infection and Tuberculosis Disease: A Systematic Review and Meta-Analysis of Epidemiological Studies.

BACKGROUND: Tuberculosis is one of the leading causes of mortality worldwide from an infectious disease. This review aimed to investigate the association between prior cytomegalovirus infection and tuberculosis disease. METHODS: Six bibliographic databases were searched from their respective inception to 31 December 2021. Data were pooled using random-effects meta-analysis. RESULTS: Of 5476 identified articles, 15 satisfied the inclusion criteria with a total sample size of 38 618 patients. Pooled findings showed that individuals with cytomegalovirus infection had a higher risk of tuberculosis disease compared to those not infected with cytomegalovirus (odds ratio [OR], 3.20; 95% confidence interval [CI], 2.18-4.70). Age was the only covariate that exerted a significant effect on the result of the association. Meta-analysis of risk estimates reported in individual studies showed a marked and significant correlation of cytomegalovirus infection with active tuberculosis (adjusted hazard ratio, 2.92; 95% CI, 1.34-4.51; adjusted OR, 1.14; 95% CI, .71-1.57). A clear dose-response relation was inferred between the levels of cytomegalovirus antibodies and the risks of tuberculosis events (OR for high levels of cytomegalovirus antibodies, 4.07; OR for medium levels of cytomegalovirus antibodies, 3.58). CONCLUSIONS: The results suggest an elevated risk of tuberculosis disease among individuals with a prior cytomegalovirus infection.

The coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 in Malaysia.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists' readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges. OBJECTIVE: This study aims to examine community pharmacists' views on their work environment, policies and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic. SETTING: An online survey of pharmacists practising in community pharmacy setting in Malaysia. METHOD: A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilising a snowball sampling method. MAIN OUTCOME MEASURE: Community pharmacists' perceptions on safety, resilience, organisational support, and pharmaceutical services offered during COVID-19 pandemic. RESULTS: A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitisers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services. CONCLUSION: The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.

N-Acetylcysteine as Adjuvant Therapy for COVID-19 - A Perspective on the Current State of the Evidence.

The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.

Home environmental interventions for prevention of respiratory tract infections: a systematic review and meta-analysis.

OBJECTIVES: Poor housing conditions have been associated with increased risks of respiratory infections. This review aims to determine whether modifying the physical environment of the home has benefits in reducing respiratory infections. CONTENT: We performed a systematic review and meta-analysis of the effectiveness of home environmental interventions for preventing respiratory tract infections. Ten electronic databases were searched to identify randomized controlled trials published from inception to July 31, 2020. Random-effects meta-analyses were used to assess the study outcomes. Our search identified 14 eligible studies across 12 countries, which comprised 87,428 households in total. The type of interventions on home environment included kitchen appliance and design, water supply and sanitation, house insulation, and home heating. Meta-analysis indicated a potential benefit of home environmental interventions in preventing overall respiratory tract infections (Absolute RR=0.89, 95% CI=0.78-1.01, p=0.07; Pooled adjusted RR=0.72, 95% CI=0.63-0.84, p<0.0001). Subgroup analyses depicted that home environmental interventions had no significant impact on lower respiratory tract infections, pneumonia, and severe pneumonia. A protective effect against respiratory infections was observed in high income country setting (RR=0.82, 95% CI=0.78-0.87, p<0.00001). SUMMARY AND OUTLOOK: Home environmental interventions have the potential to reduce morbidity of respiratory tract infections. The lack of significant impact from stand-alone housing interventions suggests that multicomponent interventions should be implemented in tandem with high-quality health systems.

Randomized trials of housing interventions to prevent malaria and Aedes-transmitted diseases: A systematic review and meta-analysis.

BACKGROUND: Mosquito-borne diseases remain a significant public health problem in tropical regions. Housing improvements such as screening of doors and windows may be effective in reducing disease transmission, but the impact remains unclear. OBJECTIVES: To examine whether housing interventions were effective in reducing mosquito densities in homes and the impact on the incidence of mosquito-borne diseases. METHODS: In this systematic review and meta-analysis, we searched 16 online databases, including NIH PubMed, CINAHL Complete, LILACS, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials for randomized trials published from database inception to June 30, 2020. The primary outcome was the incidence of any mosquito-borne diseases. Secondary outcomes encompassed entomological indicators of the disease transmission. I2 values were used to explore heterogeneity between studies. A random-effects meta-analysis was used to assess the primary and secondary outcomes, with sub-group analyses for type of interventions on home environment, study settings (rural, urban, or mixed), and overall house type (traditional or modern housing). RESULTS: The literature search yielded 4,869 articles. After screening, 18 studies were included in the qualitative review, of which nine were included in the meta-analysis. The studies enrolled 7,200 households in Africa and South America, reporting on malaria or dengue only. The type of home environmental interventions included modification to ceilings and ribbons to close eaves, screening doors and windows with nets, insecticide-treated wall linings in homes, nettings over gables and eaves openings, mosquito trapping systems, metal-roofed houses with mosquito screening, gable windows and closed eaves, and prototype houses using southeast Asian designs. Pooled analysis depicted a lower risk of mosquito-borne diseases in the housing intervention group (OR = 0.68; 95% CI = 0.48 to 0.95; P = 0.03). Subgroup analysis depicted housing intervention reduced the risk of malaria in all settings (OR = 0.63; 95% CI = 0.39 to 1.01; P = 0.05). In urban environment, housing intervention was found to decrease the risk of both malaria and dengue infections (OR = 0.52; 95% CI = 0.27 to 0.99; P = 0.05).Meta-analysis of pooled odds ratio showed a significant benefit of improved housing in reducing indoor vector densities of both Aedes and Anopheles (OR = 0.35; 95% CI = 0.23 to 0.54; P<0.001). CONCLUSIONS: Housing intervention could reduce transmission of malaria and dengue among people living in the homes. Future research should evaluate the protective effect of specific house features and housing improvements associated with urban development.

Attitudes towards deprescribing among multi-ethnic community-dwelling older patients and caregivers in Malaysia: a cross-sectional questionnaire study. A Comment.

Understanding older adult and caregiver attitudes towards deprescribing will contribute to medication optimization in clinical practice. The objectives of this study were to explore quantitatively the attitudes and beliefs of older adults and caregivers towards deprescribing and identify participant characteristics that were associated with willingness to have a medication deprescribed. This study was conducted in a government-led primary care health clinic and three private community pharmacies in Malaysia with older adults and caregivers of older adults. The revised patients' attitudes towards deprescribing (rPATD) questionnaire was administered. The rPATD questionnaire had four factors in both older adults' and caregivers' versions of the questionnaire (with four to five questions retained in each factor) alongside two global questions that were not included in any of the scoring factors. Our revised statement of main findings now states that most of older adult (n = 340, 67.7%) and caregiver (n = 34, 65.4%) participants agreed or strongly agreed that they would be willing to stop one or more of their or their care recipient's medications if their or their care recipient's doctor said it was possible to do so.

Prevalence of potentially inappropriate medications among geriatric residents in nursing care homes in Malaysia: a cross-sectional study.

Background Polypharmacy has been associated with an increased risk of morbidity and mortality among older adults especially those living in nursing homes. Explicit criteria to evaluate the appropriateness of medications have recently been updated. Objective To estimate and compare the prevalence of potentially inappropriate medications (PIMs) among older adults in nursing homes using screening tool for older people's prescription (STOPP-2) and the 2015 Beers criteria. Setting Nursing care homes in the Klang Valley, Malaysia. Method A cross-sectional survey of medications used among residents living in nursing homes was performed. The 2015 Beers criteria and STOPP-2 criteria were used to evaluate the use of PIMs among this population. These PIMs were subsequently classified using the Pharmaceutical Network Europe classification (PCNE). Main outcome measure Number of PIMs among residents using both criteria. Results A total of 155 residents were recruited into the study. The prevalence of PIMs was 9.7% using the STOPP-2 criteria, 17.6% using the 2015 Beers criteria and 21.3% when both tools were used in combination. The PCNE criteria identified a total of 198 drug related issues, with an average of 1.27 issue per resident. Factors associated with higher risk of having PIM include multiple medication use and history of psychiatric disorder. Conclusion The 2015 Beers criteria was able to identify more PIM's compared to STOPP-2 criteria. The findings also support the expansion of pharmacists' services in nursing homes in Malaysia.

Attitudes towards deprescribing among multi-ethnic community-dwelling older patients and caregivers in Malaysia: a cross-sectional questionnaire study.

Background Deprescribing describes a process of medication regimen optimization with the aim to reduce adverse events and improve quality of life. There is limited research on perceptions of older adults, defined as those 60 years of age and older, about their willingness to cease a medication in developing countries. Objective To ascertain patients' attitudes, beliefs, perceptions, and experiences regarding the number of medications they were taking and their opinions regarding deprescribing. Setting A primary care health clinic and three community pharmacies in Malaysia. Method A multicenter cross-sectional study was conducted by administering the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire to older adults aged 60 years and over or caregivers attending a health clinic and three community pharmacies in Malaysia. Descriptive results were reported for participants' characteristics and questionnaire responses. Analysis of correlation between participant characteristics and their responses was performed using Spearman's correlation. Main outcome measure Patients' and caregivers' attitudes and beliefs towards reducing medications and characteristics of patients such as age, gender, education level, number of medication taken and number of medical center managing the patient. Results 650 participants were approached and the response rate was 85.2%. A total of 554 participants completed the questionnaire (502 older adults and 52 caregivers). Older adults in the study were taking a median of three medications and/or supplements compared to four in caregiver recipients. 88.1% of older adults were satisfied with their current medication regimen and 67.7% would like to try stopping or reducing the dose of their medicines when their doctor recommended. 82.7% of caregivers were satisfied with their care recipient's current medications and 65.4% were willing to stop taking or reduce the number of drugs taken by their care recipient's upon doctor's recommendation. Older adults (p = 0.003) and those with lower education level (p < 0.001) were more willing to have their medications deprescribed. Other demographic characteristics such as gender, number of medication taken or number of doctors managing patient were not found to be correlated with willingness to stop a medication. Conclusion Older adults taking multiple medications for various medical conditions were largely accepting of a trial of cessation of medication.

Systematic Review of the Safety and Efficacy of Palivizumab among Infants and Young Children with Cystic Fibrosis.

BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care for infants with CF remains controversial. OBJECTIVE: To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years. METHODS: Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis. RESULTS: The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880). CONCLUSIONS: Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF.

Complementary and alternative medicine for the treatment of bronchiolitis in infants: A systematic review.

BACKGROUND: Bronchiolitis is a common cause of hospitalization among infants. The limited effectiveness of conventional medication has prompted the use of complementary and alternative medicine (CAM) as alternative or adjunctive therapy for the management of bronchiolitis. AIMS: To determine the effectiveness and safety of CAM for the treatment of bronchiolitis in infants aged less than 2 years. METHODS: A systematic electronic search was performed in Medline, Embase, CINAHL, AMED, and Cochrane Central Register of Controlled Trials (CENTRAL) from their respective inception to June 30, 2016 for studies evaluating CAM as an intervention to treat bronchiolitis in infants (1 month to 2 years of age). The CAM could be any form of treatment defined by the National Center for Complementary and Integrative Health (NCCIH) and was utilized either as a single agent or adjunctive therapy. The predefined primary outcome was length of hospital stay. Secondary outcomes were time to resolution of bronchiolitis symptoms, adverse events, and all other clinical outcomes reported by the included studies. RESULTS: The review identified 11 studies (8 randomized controlled trials and 3 cohort studies) examining four herbal preparations and four supplements used either as adjunctive or alternative therapy for bronchiolitis in 904 infants. Most studies were of moderate quality. Among six studies reporting on length of stay, a significant benefit was found for Chinese herbal medicine compared to ribavirin in one cohort study (n = 66) and vitamin D compared to placebo in one randomized controlled trial (n = 89). Studies of Chinese herbal medicine (4 studies, n = 365), vitamin D (1 study, n = 89), N-acetylcysteine (1 study, n = 100), and magnesium (2 studies, n = 176) showed some benefits with respect to clinical severity scores, oxygen saturation, and other symptoms, although data were sparse for any single intervention and the outcomes assessed and reported varied across studies. Only five studies reported on adverse events; no serious adverse events were reported. CONCLUSIONS: Among 11 studies examining the effect of CAM on inpatients with bronchiolitis, six reported on the review's primary outcome of length of hospital stay. In general, findings did not show a significant benefit associated with the primary outcome. Preliminary evidence indicated that Chinese herbal medicine mixtures, vitamin D, N-acetylcysteine, and magnesium might be useful in managing the symptoms of bronchiolitis. However, the evidence was not sufficient or rigorous enough to formulate recommendations for the use of any CAM. Among studies that reported adverse events, no serious harms were noted.

Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates.

AIMS: This study evaluated the therapeutic outcomes of early versus late caffeine therapy in preterm neonates. METHODS: We performed a systematic literature search in PubMed, Embase, CINAHL and CENTRAL from inception to 30 June 2016 to identify studies investigating the use of early caffeine therapy (initiated at less than 3 days of life) in preterm infants. Effect estimates were combined using random-effects meta-analysis. The primary outcomes for this study were bronchopulmonary dysplasia and mortality. RESULTS: The initial search found 4066 citations, of which 14 studies enrolling a total of 64 438 participants were included. The time of initiation of early caffeine therapy varied from the first 2 h to 3 days postnatal. Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81). In cohort studies, neonates treated early with caffeine also showed decreased risks of patent ductus arteriosus, brain injury, retinopathy of prematurity and postnatal steroid use. However, the mortality rate was increased. CONCLUSIONS: The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.