A systematic review and meta-analysis of the association between e-cigarette use among non-tobacco users and initiating smoking of combustible cigarettes.

INTRODUCTION: The rapid increase in e-cigarette use over the past decade has triggered an important public health question on the potential association between e-cigarette use and combustible cigarette smoking. Following AMSTAR 2 and PRISMA guidelines, this evidence synthesis sought to identify and characterize any associations between e-cigarette use among individuals not smoking cigarettes and initiation of cigarette smoking. METHODS: The protocol was registered on September 24, 2018 (PROSPERO 2018 CRD42018108540). Three databases were queried from January 01, 2007 to April 26, 2023. Search results were screened using the PICOS review method. RESULTS: Among 55 included studies (40 "good" and 15 "fair"; evidence grade: "high") that adjusted for gender, age, and race/ethnicity between groups, generally, there was a significant association between non-regular e-cigarette use and initiation of cigarette smoking, further supported by the meta-analytic results (AOR 3.71; 95% CI 2.86-4.81). However, smoking initiation was most often measured as ever/current cigarette smoking. Two studies (quality: 2 "good") evaluated progression to regular cigarette smoking among individuals with regular use of e-cigarettes, and generally found no significant associations. One study ("good") evaluated smoking initiation among individuals with regular use of e-cigarettes, finding an increasing probability of ever smoking cigarettes with increased e-cigarette use. Twelve studies (10 "good" and two "fair") examining progression to regular smoking among individuals with non-regular use of e-cigarettes reported inconsistent findings. CONCLUSIONS: Numerous methodological flaws in the body of literature limit the generalizability of these results to all individuals who are not smoking cigarettes with few studies measuring established/regular use/smoking of e-cigarettes and cigarettes. Further, studies did not control adequately for specific confounding variables representing common liabilities between e-cigarette use and cigarette smoking, nor did they account for sufficient follow-up durations. Collectively, these flaws limit the generalizability of findings to the question of an association between e-cigarette use and cigarette smoking initiation.

A Systematic Review Investigating Associations Between E-Cigarette Use Among Former Cigarette Smokers and Relapse to Smoking Cigarettes.

As e-cigarette use has steadily increased over the recent years, the public health interest in the potential implications of e-cigarette use on cigarette smoking has grown in parallel. With strict adherence to PRISMA guidelines, this systematic review examined the potential associations between e-cigarette use and relapse to cigarette smoking among former cigarette smokers. The protocol was registered on November 06, 2018 (PROSPERO 2018 CRD42018115674). Literature searches were executed from January 01, 2007 to August 20, 2022 and search results were screened according to the PICOS review method. One RCT and 10 adjusted studies examined relapse to cigarette smoking (evidence grade "moderate") among regular e-cigarette users, reporting mixed and inconsistent findings according to varying definitions of e-cigarette use and relapse. Findings were similarly inconsistent among the 8 adjusted studies examining relapse to cigarette smoking among non-regular e-cigarette users. The inconsistency in findings among studies evaluating regular measures of e-cigarette use, combined with the numerous methodological flaws in the overall body of literature, limit the generalizability of results associated with a causal association between e-cigarette use and relapse to cigarette smoking. Based on findings from this review, more robust studies are required to determine whether a causal association exists between e-cigarette use and relapse to cigarette smoking. Future studies should apply consistent measures of regular e-cigarette use to examine causality with future use patterns, and sufficiently account for known or suspected confounding variables to support inform determinations related to e-cigarette use and cigarette smoking behaviors.

Study title: A systematic review of RCTs to examine the risk of adverse cardiovascular events with nicotine use.

Associations between cigarette smoking and increased risk of cardiovascular disease are well established. However, it is unclear whether the association is mediated by exposure to nicotine and/or to other constituents in cigarette smoke. The objective of this systematic review and meta-analysis of randomized control trials (RCTs) was to identify any potential associations between exposure to nicotine and the risk of clinically diagnosed adverse cardiovascular events in adult current users and nonusers of tobacco products. Among 1,996 results, 42 studies, comparing nicotine and non-nicotine groups, were included and were both qualitatively and quantitatively synthesized across the outcomes of arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The majority of studies evaluating nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death reported no events that occurred in either the nicotine or non-nicotine control groups. Among the studies that reported events, rates of adverse events were similarly low between both groups. Consistent with findings from previous systematic reviews and meta-analyses, pooled data showed that rates for arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were not significantly different between nicotine and non-nicotine groups. The overall quality of the body of evidence for each of the four outcomes of interest was graded as "moderate," limited only by the imprecision of results. The findings of this systematic review and meta-analysis indicate that, with moderate certainty, there are no significant associations between the use of nicotine and the risk of clinically diagnosed adverse cardiovascular events-specifically, arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer.

Background: The association between cigarette smoking and the increased risk of many cancers is well established. Conversely, epidemiological studies of smokeless tobacco demonstrate decreased risk, or no elevated risk, of certain cancers versus smoking. However, it is unclear what role, if any, nicotine plays in these associations. The objective of this systematic review was to synthesize the available evidence from preclinical studies that examined the potential association between nicotine and the initiation and/or progression of cancer. Methods: MEDLINE, Embase, PsychInfo, and Cochrane Database of Systematic Reviews were searched for articles published from inception until February 13, 2022. Studies were eligible for inclusion if they evaluated animal cancer or tumor models, compared nicotine and non-nicotine groups, and evaluated measures of cancer initiation or progression. Results: Among 1,137 identified articles, 61 were included in qualitative synthesis. Twelve studies reported data on tumor initiation, and 54 studies reported data on tumor progression. The majority of the tumor initiation studies did not identify an association between nicotine exposure and an increased risk of spontaneous tumor initiation. Results of tumor progression studies were inconsistent and varied across the reported measures, cancer type being evaluated, and animal cancer model used. Overall, the quality of reporting was poor, with many studies not demonstrating a high level of internal and/or external validity. Conclusions: In conclusion, although animal models have provided invaluable data for human health risk assessments of chemical exposures, the heterogeneity across the studies included in this systematic review make the interpretation and generalizability of the results difficult.

Estimating the EQ-5D-5L value set for the Philippines.

BACKGROUND: The Philippines has recommended the use of Quality-Adjusted Life Years (QALYs) in government health technology assessments (HTA). We aimed to develop a value set for the EQ-5D-5L based on health preferences of the healthy general adult population in the Philippines. METHODS: Healthy, literate adults were recruited from the Philippine general population with quota targets based on age, sex, administrative region, type of residence, education, income, and ethnolinguistic groups. Each participant's preference was elicited by completing Composite Time Trade-Off (C-TTO) and Discrete Choice Experiment (DCE) tasks. Tasks were computer-assisted using the EuroQol Valuation Technology 2.0. To estimate the value set, we explored 20- and 8-parameter models that either use c-TTO-only data or both c-TTO and DCE (also called hybrid models). Final model choice was guided by principles of monotonicity, out-of-sample likelihood, model fit, and parsimony. RESULTS: We recruited 1000 respondents with demographic characteristics that approximate the general population such as 49.6% Female, 82% Roman Catholic, 40% in urban areas, and 55% finished high school. None of the 20-parameter models demonstrated monotonicity (logical worsening of coefficients with increasing severity). From the 8-parameter models, the homoscedastic TTO-only model exhibited the best fit. From this model, mobility and pain/ discomfort had the highest effect on utilities. CONCLUSION: The selected model for representing the Philippine general population preferences for EQ-5D-5L health states was an 8-parameter homoscedastic TTO-only model. This value set is recommended for use in QALY calculations in support of HTA-informed coverage decisions in the Philippines.

A cross-sectional study on the determinants of health-related quality of life in the Philippines using the EQ-5D-5L.

PURPOSE: The purpose of this study was to identify the determinants of Filipinos' health-related quality of life (HRQoL). METHODS: Data were collected from 1000 Filipinos across the nation who reported that they did not have known active disease or disability. HRQoL was measured through EuroQoL's (EQ) 5-level tool (EQ-5D-5L) and the EQ Visual Analog Scale (EQ-VAS). Both were implemented via the EQ Valuation Technology software. HRQoL was regressed on socioeconomic characteristics (age, sex, marital status, educational attainment, employment, poverty status, and availability of savings), social support factors (religion, religious attendance, and caregiving status), community- or societal-level factors (type and major island group of residence), and disease status. RESULTS: Majority of respondents reported that they did not have any problems across all EQ-5D-5L dimensions, namely mobility, self-care, usual activity, pain or discomfort, and anxiety or depression. Pain or discomfort had the highest rate of respondents reporting slight to extreme problems followed by anxiety or depression. Having savings was positively associated with HRQoL, while religious attendance, caregiver status, living in an urban area, living in Visayas or Mindanao, and having a diagnosed disease were negatively associated with HRQoL. CONCLUSION: This current study confirms that HRQoL varied across socioeconomic statuses and communities in the Philippines.

Guidelines in Low and Middle Income Countries Paper 3: Appraisal of Philippine Clinical Practice Guidelines using Appraisal of Guidelines for Research and Evaluation II: improvement needed for rigor, applicability, and editorial independence.

BACKGROUND AND OBJECTIVE: High-quality clinical practice guidelines (CPGs) are needed to guide practitioners, policy makers, and other stakeholders to provide optimal health care. This study aims to appraise the CPGs developed in the Philippines using the AGREE II instrument. METHODS: Ninety-one CPGs were appraised independently by two health-care professionals. CPGs were considered acceptable if they garnered an overall mean score of at least 75.0% for all 6 domains and a domain score of at least 75.0% for rigor of development. A mean score of <75.0% on either of the criteria implied that the CPG needed revision. RESULTS: Overall mean scores of the CPGs ranged from 8.4% to 79.2%, with a mean of 43.9% (standard deviation = 13.4%). In general, CPGs scored better for the domains of clarity of presentation, scope and purpose, and stakeholder involvement. Lowest scores were obtained for the domains of rigor of development, applicability, and editorial independence. Only 1 (1.1%) CPG qualified as acceptable. CONCLUSION: AGREE II is a practical and useful guide in appraising the quality of CPGs. Strengthening technical capacity in various medical fields is essential to improve the quality of CPGs. Rigor of development, applicability issues, and editorial independence should be emphasized in CPG capacity-building activities.

Appraisal of the methodological quality of clinical practice guidelines in the Philippines.

PURPOSE: The Republic of the Philippines has recently enacted the Universal Health Care Law, which mandates the Philippines Department of Health (DOH) to operationalize evidence-based clinical practice guideline (CPG) development. As a baseline to the foregoing task, the aim of this study was to appraise the methodological quality of CPGs previously developed and currently being disseminated in the Philippines. A multimethod search for CPGs was implemented. CPGs were independently evaluated using a modified version of the Knowledge Management Plus CPG appraisal tool. FINDINGS: Eighty-seven CPGs were included in the appraisal. Majority implemented processes to ensure validity, ie, consideration for patient groups, management options, benefits, and harms (99%), and indicated strength of their recommendations (89%). Seventy-seven CPGs (89%) evaluated the evidence for local applicability. Of the 87 CPGs, 20 CPGs (23%) considered equity in the development process. The development process differed among CPGs with varying degrees of utilization of GRADE methodology (52%), disclosure of funding sources (72%), and engagement of technical support external to the development body (3%). Mean duration of CPG development was 1 year (SD 5.9 months), and mean interval between updates was 6 years and 1 month (SD 37.8 months). CONCLUSION: Although most of the CPGs fulfilled essential criteria for quality recommendations (validity and applicability), equity considerations were limited. Furthermore, only half used the GRADE approach and development and dissemination practices differed substantially between CPGs. Thus, it is recommended that a standard CPG development process be made available by the DOH to be utilized by CPG developers in the Philippines.

Ethical Challenges in Medical Community Internships: Perspectives from Medical Interns in the Philippines.

The Philippine community internship program, originally created to supplement the country's thinning health workforce while providing training to student doctors, poses a legal and ethical challenge for medical interns. Inherent characteristics of the program-such as financial disparities and burdens, the lack of supervision by senior doctors, the competence of student doctors, and short rotation times-can predispose interns to cause harm to the patients and communities they serve. As currently designed, the internship program has the capacity to leave interns unsupervised, at risk of legal ramifications, constantly questioning the correctness of their interventions, and perpetually straddling conflicting role virtues. By failing to ensure that the community internship program has appropriate safeguards in place, the government not only jeopardizes the welfare of interns but also threatens the quality and continuity of care that patients and communities receive, potentially violating their right to the highest attainable standard of health. One medical school recently started a novel internship program that could address the issues mentioned.

Incidence, risk factors, and outcomes of unplanned extubation in adult patients in a resource-limited teaching hospital in the Philippines: a cohort study. / Incidência, fatores de risco e desfechos da extubação não planejada em pacientes adultos em um hospital de ensino com recursos limitados nas Filipinas: um estudo de coorte.

OBJECTIVE: We aimed to determine the incidence, risk factors, and outcomes of unplanned extubation among adult patients. METHODS: We conducted a prospective cohort study of adult intubated patients admitted to the charity wards of a government tertiary teaching hospital in the Philippines. Patients managed in both intensive care and nonintensive care settings were included. Patients were followed-up until discharge or until seven days postextubation. RESULTS: The outcomes of the 191 included patients were planned extubation (35%), unplanned extubation (19%), death (39%), and discharge against advice (7%). Competing risk regression showed that male sex (Crude OR: 2.25, 95%CI: 1.10 - 4.63) and age (Crude OR 0.976, 95%CI: 0.957 - 0.996) were significant baseline factors. The night shift (Crude OR: 24.6, 95%CI: 2.87 - 211) was also consistently associated with more unplanned extubations. Among postextubation outcomes, reintubation (unplanned extubation: 61.1% versus planned extubation: 25.4%), acute respiratory failure (unplanned extubation: 38.9% versus planned extubation: 17.5%), and cardiovascular events (unplanned extubation: 8.33% versus planned extubation: 1.49%) occurred significantly more often among the unplanned extubation patients. Admission in an intensive care unit was not associated with a lower risk of unplanned extubation (Crude OR 1.15, 95%CI: 0.594 - 2.21). CONCLUSION: Many intubated patients had unplanned extubation. Patients admitted in nonintensive care unit settings did not have significantly higher odds of unplanned extubation.

OBJETIVO: Determinar a incidência, os fatores de risco e os desfechos da extubação não planejada em pacientes adultos. MÉTODOS: Conduzimos estudo prospectivo de coorte de pacientes adultos intubados admitidos em ala de atendimento gratuito em um hospital governamental terciário de ensino nas Filipinas. Incluíram-se tanto pacientes em cuidados de terapia intensiva quanto fora dela. Os pacientes foram seguidos até a alta ou até o sétimo dia após a extubação. RESULTADOS: Os desfechos dos 191 pacientes incluídos foram: extubação planejada (35%), extubação não planejada (19%), óbito (39%) e alta a pedido (7%). A regressão de riscos competitivos demonstrou que o sexo masculino (OR bruta de 2,25; IC95% 1,10 - 4,63) e a idade (OR bruta: 0,976; IC95%: 0,957 - 0,996) foram fatores basais significantes. O turno da noite (OR bruta: 24,6; IC95%: 2,87 - 211) também teve associação consistente com maior ocorrência de extubação não planejada. Dentre os desfechos após a extubação, ocorreram significantemente mais, entre os pacientes com extubação não planejada, reintubação (extubação não planejada, com 61,1%, versus extubação planejada, com 25,4%), insuficiência respiratória aguda (extubação não planejada, com 38,9%, versus extubação planejada, com 17,5%) e eventos cardiovasculares (extubação não planejada, com 8,33%, versus extubação planejada, com 1,49%). A admissão à unidade de terapia intensiva não se associou com risco menor de extubação não planejada (OR bruta de 1,15; IC95% 0,594 - 2,21). CONCLUSÃO: Muitos pacientes intubados tiveram extubação não planejada. Os pacientes admitidos em outras unidades, que não a de terapia intensiva, não tiveram tendências mais elevadas de extubação não planejada.

Incidência, fatores de risco e desfechos da extubação não planejada em pacientes adultos em um hospital de ensino com recursos limitados nas Filipinas: um estudo de coorte / Incidence, risk factors, and outcomes of unplanned extubation in adult patients in a resource-limited teaching hospital in the Philippines: a cohort study

RESUMO Objetivo: Determinar a incidência, os fatores de risco e os desfechos da extubação não planejada em pacientes adultos. Métodos: Conduzimos estudo prospectivo de coorte de pacientes adultos intubados admitidos em ala de atendimento gratuito em um hospital governamental terciário de ensino nas Filipinas. Incluíram-se tanto pacientes em cuidados de terapia intensiva quanto fora dela. Os pacientes foram seguidos até a alta ou até o sétimo dia após a extubação. Resultados: Os desfechos dos 191 pacientes incluídos foram: extubação planejada (35%), extubação não planejada (19%), óbito (39%) e alta a pedido (7%). A regressão de riscos competitivos demonstrou que o sexo masculino (OR bruta de 2,25; IC95% 1,10 - 4,63) e a idade (OR bruta: 0,976; IC95%: 0,957 - 0,996) foram fatores basais significantes. O turno da noite (OR bruta: 24,6; IC95%: 2,87 - 211) também teve associação consistente com maior ocorrência de extubação não planejada. Dentre os desfechos após a extubação, ocorreram significantemente mais, entre os pacientes com extubação não planejada, reintubação (extubação não planejada, com 61,1%, versus extubação planejada, com 25,4%), insuficiência respiratória aguda (extubação não planejada, com 38,9%, versus extubação planejada, com 17,5%) e eventos cardiovasculares (extubação não planejada, com 8,33%, versus extubação planejada, com 1,49%). A admissão à unidade de terapia intensiva não se associou com risco menor de extubação não planejada (OR bruta de 1,15; IC95% 0,594 - 2,21). Conclusão: Muitos pacientes intubados tiveram extubação não planejada. Os pacientes admitidos em outras unidades, que não a de terapia intensiva, não tiveram tendências mais elevadas de extubação não planejada.

ABSTRACT Objective: We aimed to determine the incidence, risk factors, and outcomes of unplanned extubation among adult patients. Methods: We conducted a prospective cohort study of adult intubated patients admitted to the charity wards of a government tertiary teaching hospital in the Philippines. Patients managed in both intensive care and nonintensive care settings were included. Patients were followed-up until discharge or until seven days postextubation. Results: The outcomes of the 191 included patients were planned extubation (35%), unplanned extubation (19%), death (39%), and discharge against advice (7%). Competing risk regression showed that male sex (Crude OR: 2.25, 95%CI: 1.10 - 4.63) and age (Crude OR 0.976, 95%CI: 0.957 - 0.996) were significant baseline factors. The night shift (Crude OR: 24.6, 95%CI: 2.87 - 211) was also consistently associated with more unplanned extubations. Among postextubation outcomes, reintubation (unplanned extubation: 61.1% versus planned extubation: 25.4%), acute respiratory failure (unplanned extubation: 38.9% versus planned extubation: 17.5%), and cardiovascular events (unplanned extubation: 8.33% versus planned extubation: 1.49%) occurred significantly more often among the unplanned extubation patients. Admission in an intensive care unit was not associated with a lower risk of unplanned extubation (Crude OR 1.15, 95%CI: 0.594 - 2.21). Conclusion: Many intubated patients had unplanned extubation. Patients admitted in nonintensive care unit settings did not have significantly higher odds of unplanned extubation.