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Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent.

Studies often combine several events, for example, death or myocardial infarction or stroke, into a single study outcome. This is called a composite endpoint. Composite endpoints make doing trials easier by reducing the sample size or follow-up period required to demonstrate the effectiveness of an intervention. However, interpreting the results of composite endpoints can be confusing. To avoid misleading conclusions about the effectiveness of an intervention, it is important for readers of studies reporting a composite endpoint to ascertain that the clinical importance, the frequency of events, and the effect of the intervention on each component of the composite endpoint are similar. •Studies often combine several events into a single study outcome, the composite endpoint.•Using composite endpoints reduces the sample size or follow-up period required to demonstrate the effectiveness of an intervention.•To avoid misleading conclusions about the effectiveness of an intervention, it is important to ascertain that the clinical importance, the frequency of events, and the effect of the intervention on each component of the composite endpoint are similar.

Information on the magnitude and durability of humoral immunity against COVID-19 among specific populations can guide policies on vaccination, return from isolation and physical distancing measures. The study determined the durability of SARS-CoV-2 antibodies after an initial infection among Filipinos in Metro Manila, Philippines, and the extent of protection SARS-CoV-2 antibodies confer against reinfection. We conducted a cohort study to monitor the antibody levels of patients diagnosed with COVID-19. Receptor-binding domain (RBD)-specific antibodies were measured at Days 21, 90, 180, 270 and 360. Antibody levels were reported as geometric mean titers (GMT) with geometric standard deviation (GSD). Differences in GMT were tested using Friedman test and Kruskal Wallis test, with Bonferroni multiple comparisons procedure. Adjusted hazard ratios on the development of probable reinfection were estimated using Cox proportional models. There were 307 study participants included in the study, with 13 dropouts. Study participants received SARS-CoV-2 vaccines at varying times, with 278 participants (90.5%) fully vaccinated by the end of study. The GMT of the study cohort increased over time, from 19.7 U/mL (GSD 11) at Day 21; to 284.5 U/mL (GSD 9.6) at Day 90; 1,061 U/mL (GSD 5.3) at Day 180; 2,003 U/mL (GSD 6.7) at Day 270; and 8,403 U/mL (GSD 3.1) at Day 360. The increase was statistically significant from Day 21 to Day 90 (p<0.0001), Day 90 to Day 180 (p=0.0005), and Day 270 to Day 360 (p<0.0001). Participants with more severe initial infection demonstrated significantly higher antibody levels compared to those with milder infection at Day 21. Sixty-four patients had probable COVID-19 reinfection (incidence of 20.8%, 95% CI 16.4, 25.8%). The GMT of these 64 patients was 411.8 U/mL (GSD 6.9) prior to the occurrence of the probable reinfection. Majority (87.5%) were fully vaccinated. Antibody titers significantly affected the risk of developing reinfection, with adjusted hazard ratio of 0.994, 95% CI 0.992-0.996, p<0.001. Antibody levels against SARS-CoV-2 increased over a one-year follow-up. Higher antibody levels were observed among those with more severe initial infection and those vaccinated. Higher antibody levels are associated with a lower risk of probable reinfection.

ObjectivesWe aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study.MethodsWe defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1—all three drug types were available and affordable, group 2—all three drugs were available but not affordable and group 3—all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors.ResultsOf 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50).ConclusionLower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

In a meta-analysis, a question always arises. Is it worthwhile to combine estimates from studies of different populations using various formulations of an intervention, evaluating outcomes measured differently? Sometimes even study designs differ. Differences are expected in a meta-analysis. These may be negligible, and a pooled estimate of effect can guide the clinical decision. However, when the differences are large, this estimate may mislead. Effect estimates from study to study differ because of real differences (between-study variability) and because of chance (within-study variability). To combine estimates when there is heterogeneity (between-study differences are large) may not be sensible. Two complementary methods may be used to detect heterogeneity: visual inspection of the forest plot and calculating numerical measures of heterogeneity (I2 and Q). Visual inspection can show effects that are different from the rest. A large I2 (proportion of overall variability attributed to between-study variation) or a small P-value associated with Q may suggest heterogeneity. Large P-values, however, do not mean the absence of heterogeneity. It is more informative to report the confidence interval of the I2. If there is no heterogeneity, a pooled estimate of the true effect may be generated using only within-study variation (fixed-effect model). If there is substantial heterogeneity, reasons should be sought. Subgroup analysis or meta-regression using study-level characteristics may be done. Although more involved and potentially challenging, individual-level data (Individual Participant Data, IPD) may also be used. In the case of unexplained heterogeneity, both within- and between-study variation should be used to generate a pooled estimate (random-effects model). This estimate does not estimate a single true effect but estimates the average of a range of effects of the intervention on populations represented by the studies. If precise enough (narrow confidence interval), this estimate, together with the prediction interval (a measure of uncertainty in the effect one might see in a particular context), can guide clinical and policy decisions. •While differences are expected in a meta-analysis, these may be negligible, and a pooled estimate can guide the clinical decision. However, when the differences are large, this estimate may mislead.•The danger of reporting pooled estimates is that readers may overlook the overall picture—some studies having bigger effects than the other studies, some effects with different directions (harm) from the benefit shown by most studies. A careful inspection of the forest plot can help detect these differences; we refer to as heterogeneity.•Visual inspection should be used together with measures of heterogeneity–I2 and Q. High values of I2 and small P-values associated with Q may suggest heterogeneity. But large P-values do not mean the absence of heterogeneity. It is more informative to report the confidence interval of I2.•If heterogeneity is detected, an explanation must be sought, and analysis using study-level characteristics (subgroup analysis or meta-regression) may be done. Although intensive, analysis using individual-level data (Individual Participant Data) may also be done.•In case of unexplained heterogeneity, a pooled estimate using the random-effects model may be used. This estimate no longer estimates a single unknown effect but the average of the effects of the intervention in the populations represented by the studies. If precise enough (narrow confidence interval), this estimate, together with the prediction interval (a measure of uncertainty in the effect one might see in a particular context), can guide clinical and policy decisions.

Background Traditional, complementary and alternative medicine (TCAM) is used to treat a broad range of conditions. In low- and middle-income countries (LMICs), TCAM use is particularly common among those with low socio-economic status. To better understand the patterns and impact of TCAM use on the management of non-communicable diseases in these populations, this study examines the prevalence and characteristics of TCAM use for hypertension, its determinants, and its association with hypertension management outcomes and wellbeing among low-income adults in two Southeast Asian countries at different levels of economic and health system development, Malaysia and the Philippines. Methods We analysed cross-sectional data from 946 randomly selected adults diagnosed with hypertension from low-income rural and urban communities in Malaysia ( n  = 495) and the Philippines ( n  = 451). We compared the prevalence, characteristics and household expenditure on TCAM use between countries and used multi-level, mixed-effects regression to estimate associations between TCAM use and its determinants, and five hypertension management outcomes and wellbeing. Results The prevalence of TCAM use to manage hypertension was higher in the Philippines than in Malaysia (18.8% vs 8.8%, p  < 0.001). Biologically-based modalities, e.g. herbal remedies, were the most common type of TCAM used in both countries, mainly as a complement, rather than an alternative to conventional treatment. Households allocated around 10% of health spending to TCAM in both countries. Belief that TCAM is effective for hypertension was a positive predictor of TCAM use, while belief in conventional medicine was a negative predictor. TCAM use was not strongly associated with current use of medications for hypertension, self-reported medication adherence, blood pressure level and control, or wellbeing in either country. Conclusions A small, but significant, proportion of individuals living in low-income communities in Malaysia and the Philippines use TCAM to manage their hypertension, despite a general lack of evidence on efficacy and safety of commonly used TCAM modalities. Recognising that their patients may be using TCAM to manage hypertension will enable health care providers to deliver safer, more patient-centred care.

BackgroundThe Philippine Primary Care Studies implemented interventions that aimed to improve primary care services in selected urban, rural and remote communities. This study aims to describe trends in patient satisfaction in years 2 and 3 after implementation of primary care interventions.MethodsThis study is a serial cross-sectional study that assessed patient satisfaction under the domains of healthcare availability, service efficiency, technical competency, environment, location, health communication, handling and general perception in three primary care sites. Patient satisfaction was obtained via a 16-item questionnaire at baseline, and at 2 and 3 years after implementation. Pairwise testing was conducted to compare significant changes across sites over the time points.ResultsThere were 200 respondents per time point for each of the three sites. Despite the cessation of funding, system changes allowed significant improvements in patient satisfaction at the urban site. The improvements were noted in 12 out of 16 items in year 3 compared with baseline. These items belonged to the domains of healthcare availability, service efficiency, technical competency, health communication, handling and general perception. At the rural site, patient satisfaction decreased in 4 out of 16 items by year 3. These items belonged to the domains of handling and general perception. At the remote site, a significant decline in patient satisfaction was noted in 8 out of 16 items by year 3. These items belonged to the domains of healthcare availability, service efficiency, environment, location and health communication.DiscussionPatient satisfaction increased in the urban site and declined in the rural and remote site 3 years after implementation of a primary care system, when funding ended. This suggests that patient satisfaction in the urban centre was related more to the system improvements rather than fund augmentation.In contrast, it was more difficult to improve patient satisfaction in the rural and remote sites for two reasons. First, baseline satisfaction was much higher in these areas. This was probably because patients did not have alternative options for care and were therefore more appreciative. Second, cessation of financial aid led to an inability to sustain the system changes that were implemented on initiation. Their brief experience with primary care enhancements may have added perspective on pre-existing deficiencies they previously did not notice.ConclusionsModest financing and systemic improvements in primary care can lead to a significant increase in patient satisfaction. If funding is not sustained, however, patient satisfaction may decline significantly, especially in remote and underserved areas.

Introduction: This study determined the clinic prevalence and compared the quality of care of allergic diseases in urban, rural, and remote primary care sites. Methods: This was a retrospective review of electronic health records of all adult patients who consulted in the 3 sites from May 2019 to April 2022. Data of adult patients with allergic diseases was extracted from the 3 EHR systems operating across the participating sites using standardized Structured Query Language queries across the 3 systems. We computed the prevalence of allergic diseases among adults who consulted in primary care health facilities by dividing the number of patients diagnosed to have an allergic disease over the total number of adult patients who consulted within the 3-year study period. We compared the quality of care of patients across the 3 sites based on clinical practice guidelines using Chi-square test, Fisher’s exact test, or 1-way analysis of variance, as appropriate. Results: The prevalence of allergic disease among adults who consulted in primary care health facilities was 1.3% for the urban site, 2.2% for the rural site, and 2.1% for the remote site. The most common allergic disease was asthma (59.0%). First-line medications based on recommendations in clinical practice guidelines were prescribed more often in the urban site, including inhaled corticosteroids with long-acting beta-agonists for asthma patients (P < .001) and topical corticosteroids for atopic dermatitis (P < .001). In contrast, there was more frequent prescription of medications that were not recommended in clinical practice guidelines in the rural and remote sites. Conclusion: Health inequity was observed in this study, with results demonstrating that the rural and remote sites had greater allergic disease prevalence, greater underutilization of first-line medications, and more frequent overutilization of non-essential medications.

IntroductionUnderstanding explanatory models is important for hypertension, a leading risk factor for cardiovascular disease and stroke. This article aims to determine what adult patients with hypertension in the Philippines attribute their condition to, how these views might be explained and what the implications are for hypertension management.MethodsThis is a qualitative study drawing on 71 semistructured interviews (40 initial and 31 follow-up) and four focus group discussions with patients diagnosed with hypertension. The setting was urban and rural low-income communities in the Philippines.ResultsFour prominent perceived causes were identified—genetics, heat, stress and diet—for what patients refer to as ‘high blood’. We propose a ‘folk physiology’ that rests on local understandings of blood and blood flow, draws from broader cultural notions of illness causation and accounts for a dynamic, non-chronic view of hypertension that in turn informs the health behaviours of those affected.ConclusionsBy understanding that hypertension is frequently seen not as a chronic constant condition but rather as an episodic one triggered by external influences, although in those genetically predisposed to it, it may be possible to address patient’s beliefs and thus adherence to treatment.