GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: a living benefit-harm modelling study.

Background: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. This study aimed at evaluating the benefit-harm balance of initiating GLP-1 RAs versus placebo for weight loss in people living with overweight and obesity but without diabetes. Methods: We performed benefit-harm balance modelling, which will be updated as new evidence emerges. We searched for randomised controlled trials (RCTs) in PubMed, controlled trials registry, drug approval and regulatory documents, and outcome preference weights as of April 10, 2024. We synthesize data using pairwise meta-analysis to estimate the effect of GLP-1 RAs to inform the benefit-harm balance modelling. We predicted the absolute effects of the positive and negative outcomes over 1 and 2 years of treatment using exponential models. We applied preference weights to the outcomes, ranging from 0 for least concerning to 1.0 for most concerning. We then calculated whether the benefit of achieving 5% and 10% weight loss outweighed the harms on a common scale. The analyses accounted for the statistical uncertainties of treatment effects, preference weights, and outcome risks. Findings: We included 8 RCTs involving 8847 participants. The pooled average age was 46.7 years, with the majority being women (74%) and people living with obesity (96%). Of 1000 persons treated with GLP-1 RAs for 2 years, 375 (95% confidence interval 352 to 399) achieved a 10% weight loss, and 318 (296 to 339) achieved a 5% weight loss compared to those treated with placebo. Several harm outcomes were more frequent in the GLP-1 RA group, including 41 abdominal pain events per 1000 persons over 2 years (19 to 69), cholelithiasis (8, 1 to 21), constipation (118, 78 to 164), diarrhoea (100, 42 to 173), alopecia (57, 10 to 176), hypoglycaemia (17, 1 to 68), injection site reactions (4, -3 to 19), and vomiting (110, 80 to 145) among others. Achieving a 10% weight loss with GLP-1 RA therapy outweighed the cumulative harms, with a net benefit probability of 0.97 at year 1 and 0.91 at year 2. The absolute net benefit was equivalent to 104 (100 to 112) per 1000 persons achieving a 10% weight loss over 2 years without experiencing any worrisome harm. A 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively. However, these benefits were sensitive to preference weights, suggesting that even a 5% weight loss could be net beneficial for individuals with less concern about harm outcomes. The net benefit for a 10% weight loss was highest for semaglutide, followed by liraglutide and tirzepatide, with 2-year probabilities of 0.96, 0.72, and 0.60, respectively. Interpretation: The benefit of GLP-1 RAs exceeded the harms for weight loss in the first 2 years of treatment, yet the net benefit was dependent on individual' treatment goals (10% or 5% weight loss) and willingness to accept harms in pursuit of weight loss. This implies that treatment decisions have to be personalized to individuals to optimize benefits and reduce harms and overuse of treatments. Due to varying evidence, especially regarding harm outcomes across studies, it is necessary to continuously update and monitor the benefit-harm balance of GLP-1 RAs. Funding: SNSF and LOOP Zurich.

Benefit-Harm Analysis for Informed Decision Making on Participating in Colorectal Cancer Screening: A Modeling Study.

OBJECTIVES: To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons. METHODS: The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle. RESULTS: CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years. CONCLUSIONS: Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation.

Older adult preferences regarding benefits and harms of statin and aspirin therapy for cardiovascular primary prevention.

Objective: Personalizing preventive therapies for atherosclerotic cardiovascular disease (ASCVD) is particularly important for older adults, as they tend to have multiple chronic conditions, increased risk for medication adverse effects, and may have heterogenous preferences when weighing health outcomes. However, little is known about outcome preferences related to ASCVD preventive therapies in older adults. Methods: In May 2021, using an established online panel, KnowledgePanel, we surveyed older US adults aged 65-84 years without history of ASCVD on outcome preferences related to statin therapy (benefit outcomes to be reduced by the therapy: heart attack, stroke; adverse effects: diabetes, abnormal liver test, muscle pain) or aspirin therapy (benefit outcomes: heart attack, stroke; adverse effects: brain bleed, bowel bleed, stomach ulcer). We used standardized best-worst scores (range of -1 for "least worrisome" to +1 for "most worrisome") and conditional logistic regression to examine the relative importance of the outcomes. Results: In this study, 607 ASCVD-free participants (median age 74, 46% male, 81% White) were included; 304 and 303 completed the statin and aspirin versions of the survey, respectively. For statin-related outcomes, stroke and heart attack were most worrisome (score 0.55; 95% CI 0.51, 0.60) and (0.53; 0.48, 0.58), followed by potential harms of diabetes (-0.07; -0.10, -0.03), abnormal liver test (-0.25; -0.29, -0.20), and muscle pain (-0.77; -0.82, -0.73). For aspirin-related outcomes, stroke and heart attack were similarly most worrisome (0.48; 0.43, 0.52) and (0.43; 0.38, 0.48), followed by brain bleed (0.30; 0.25, 0.34), bowel bleed (-0.31; -0.33, -0.28), and stomach ulcer (-0.90; -0.92, -0.87). Conditional logistic regression and subgroup analyses by age, sex, and race yielded similar results. Conclusions: Older adults generally consider outcomes related to benefits of ASCVD primary preventive therapies-stroke and heart attack-more important than their adverse effects. Integrating patient preferences with risk assessment is an important next step for personalizing ASCVD preventive therapies for older adults.

Perceived Importance of the Benefits and Harms of Colorectal Cancer Screening: A Best-Worst Scaling Study.

OBJECTIVES: To elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. METHODS: In a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. RESULTS: Of 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. CONCLUSION: Dutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

Epidemiology of pre-cancerous cervical lesion and risk factors among adult women in Tigray, Ethiopia.

BACKGROUND: Cervical cancer is a preventable disease if treated early, but remains the second leading cause of cancer-related mortality among women in low and middle-income countries. Data on epidemiology and risk factors in these settings are scarce. This study aimed to assess the prevalence of pre-cancerous cervical lesions and risk factors in Tigray region, Ethiopia. METHODS: A community-based, cross-sectional study was used and 900 participants were 30 recruited using multistage sampling and finally data from 883 were collected using an interviewer administered questionnaire and screening with visual inspection with ascetic acid. Data were collected using an interviewer administered questionnaire and screening with visual inspection with acetic acid from March 2016 to June 2017. Multinomial logistic regression analysis was conducted to estimate predictors. RESULTS: Seventy-nine (8.95%) women were positive for pre-cancer lesion and 35 (3.96%) were suspicious for cervical cancer. We used relative risk ratio (rrr) to estimate the strength of association. Divorced or widowed women had 2.5 and 4.7 times more risk of being positive and suspicious respectively, compared to single women (rrr = 2.5, 95% CI [1.13, 5.52]); (rrr = 4.69, 95% CI [1.00, 21.84]). The risk of having a suspicious result was 68% lower for women with primary education compared to those with no formal education (rrr = 0.32, 95% CI [1.00, 21.84]). History of sexually transmitted infection was associated with positive pre cancer lesion (rrr = 1.91, 95% CI [1.11, 3.27]) whereas, being farmer (rrr = 4.83, 95% CI [1.44, 16.13]), merchant (rrr = 4.85, 95% CI [1.52, 15.46]), bleeding between periods (rrr = 3.26, 95% CI [1.32, 8.04]) and pelvic or back pain (rrr = 2.79, 95% CI [1.18, 6.58]) were associated with suspicious for cancer. CONCLUSION: About 8.9% and 3.96% of the women were positive for pre-cancerous cervical lesion and suspicious for cancer, respectively. The prevalence of pre-cancerous cervical lesion is high as compared to other regional prevalence in the country. Marital status, education, sexually transmitted infection, bleeding, and pelvic pain were risk factors of pre-cancerous cervical lesion'. This finding implies that the sexual exposure, having no permanent husband and being not educated attributes to the high prevalence of pre-cancerous cervical lesion and may aggravate the transmission of HPV."

Survival modelling and cost-effectiveness analysis of treatments for newly diagnosed metastatic hormone-sensitive prostate cancer.

BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC) treatment, survival benefits have been shown by adding docetaxel or recent androgen receptor axis-targeted therapies (ARATs) abiraterone, apalutamide, or enzalutamide to androgen deprivation therapy (ADT). However, the optimal treatment strategy in terms of costs and effects is unclear, not least due to high ARAT costs. METHODS: To assess treatment cost-effectiveness, we developed a Markov cohort model with health states of progression-free disease, progressive disease and death for men with newly diagnosed mHSPC, with a 30-year time horizon. Survival data, adverse events and utilities were informed by randomized controlled trial results, our meta-analysis of re-created individual patient survival data, and publicly available sources of unit costs. We applied a Swiss healthcare payer perspective and discounted costs and effects by 3%. RESULTS: We found a significant overall survival benefit for ADT+abiraterone versus ADT+docetaxel. The corresponding incremental cost-effectiveness ratio (ICER) was predicted to be EUR 39,814 per quality-adjusted life-year (QALY) gained. ADT+apalutamide and ADT+enzalutamide incurred higher costs and lower QALYs compared to ADT+abiraterone. For all ARATs, drug costs constituted the most substantial cost component. Results were stable except for a large univariable reduction in the pre-progression utility under ADT+abiraterone and very large variations in drug prices. CONCLUSIONS: Our model projected ADT+abiraterone to be cost-effective compared to ADT+docetaxel at a willingness-to-pay threshold of EUR 70,400/QALY (CHF 100,000 applying purchasing power parities). Given lower estimated QALYs for ADT+apalutamide and ADT+enzalutamide compared to ADT+abiraterone, the former only became cost-effective (the preferred) treatment option(s) at substantial 75-80% (80-90%) price reductions.

Treatments for Metastatic Hormone-sensitive Prostate Cancer: Systematic Review, Network Meta-analysis, and Benefit-harm assessment.

CONTEXT: Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear. OBJECTIVE: To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments. EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate. EVIDENCE SYNTHESIS: Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial. CONCLUSIONS: Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies. PATIENT SUMMARY: We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.

Early mobilisation and rehabilitation in Swiss intensive care units: a cross-sectional survey.

BACKGROUND: Patients in intensive care units (ICUs) are at high risk of developing physical, functional, cognitive, and mental impairments. Early mobilisation aims to improve patient outcomes and is increasingly considered the standard of care. This survey aimed to investigate the characteristics, current use and variations of early mobilisation and rehabilitation in Swiss ICUs. METHODS: We conducted a cross-sectional survey among all ICU lead physicians, who provided data on their institutional characteristics, early mobilisation and rehabilitation practices, and their perceptions of the use and variation of early rehabilitation practices in Switzerland. RESULTS: The survey response rate was 44% (37/84). Among ICUs caring for adults (34/37), 26 were in the German-speaking region, five in the French-speaking region, and three in the Italian-speaking region. All ICUs regularly involved physiotherapy in the rehabilitation process and 50% reported having a specialised physiotherapy team. All ICUs reported performing early mobilisation, starting within the first 7 days after ICU admission. About half reported the use of a rehabilitation (45%) or early mobilisation protocol (50%). Regular, structured, interdisciplinary rounds or meetings of the ICU care team to discuss rehabilitation measures and goals for patients were stated to be held by 53%. The respondents stated that 82% of their patients received early mobilisation measures during their ICU stay. Most frequently provided mobilisation measures included passive range of motion (97%), passive chair position in bed (97%), active range of motion muscle activation and training (88%), active side to side turning (91%), sitting on the edge of the bed (94%), transfer from bed to a chair (97%), and ambulation (94%). The proportion of ICUs providing a specific early mobilisation measure, the proportion of patients receiving it, and the time dedicated to it varied across language regions, hospital types, ICU types, and ICU sizes. Almost one third of the ICU lead physicians considered early rehabilitation to be underused in their own ICU and about half considered it to be underused in Switzerland more generally. ICU lead physicians stressed lack of personnel, financial resources, and time as key causes for underuse. Moreover, they highlighted the importance of early and systematic or protocol-based rehabilitation and interprofessional approaches that are adaptive to the patients' rehabilitation needs and potential. CONCLUSION: This survey suggests that almost all ICUs in Switzerland practice some form of early mobilisation with the aim of early rehabilitation. However, the described approaches, as well as the reported use of early mobilisation measures were heterogenous across Swiss ICUs.

Personalising add-on treatment with inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a benefit-harm modelling study.

BACKGROUND: Since the benefit-harm balance of adding inhaled corticosteroids to long-acting ß2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles. METHODS: Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care. FINDINGS: Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54-83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40-91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per µL, patients with a BEC of 150 cells per µL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32-95% in those aged 40-79 years and 41-93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per µL or more at 52-86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%. INTERPRETATION: The net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids. FUNDING: None.

Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients. METHODS: We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach. RESULTS: We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9-20.8) and PCS (MD 3.4; 95% CI 0.01-6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38-1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI - 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63-1.27), SF-36 PFS (MD 8.1; 95% CI - 15.3 to 31.4) or PCS (MD - 2.4; 95% CI - 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low. CONCLUSION: The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization. STUDY REGISTRATION: PROSPERO (CRD42019122555).

Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study.

BACKGROUND: We previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation. METHODS: For each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters. RESULTS: The 5th and 95th percentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19-24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5th and 95th percentiles of 14-16% for ages 40-44 years and 17-21% for ages 70-74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25-36% 10-year CVD risks. CONCLUSIONS: This extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.

Outcome preferences of older people with multiple chronic conditions and hypertension: a cross-sectional survey using best-worst scaling.

BACKGROUND: Older people with hypertension and multiple chronic conditions (MCC) receive complex treatments and face challenging trade-offs. Patients' preferences for different health outcomes can impact multiple treatment decisions. Since evidence about outcome preferences is especially scarce among people with MCC our aim was to elicit preferences of people with MCC for outcomes related to hypertension, and to determine how these outcomes should be weighed when benefits and harms are assessed for patient-centered clinical practice guidelines and health economic assessments. METHODS: We sent a best-worst scaling preference survey to a random sample identified from a primary care network of Kaiser Permanente (Colorado, USA). The sample included individuals age 60 or greater with hypertension and at least two other chronic conditions. We assessed average ranking of patient-important outcomes using conditional logit regression (stroke, heart attack, heart failure, dialysis, cognitive impairment, chronic kidney disease, acute kidney injury, fainting, injurious falls, low blood pressure with dizziness, treatment burden) and studied variation across individuals. RESULTS: Of 450 invited participants, 217 (48%) completed the survey, and we excluded 10 respondents who had more than two missing choices, resulting in a final sample of 207 respondents. Participants ranked stroke as the most worrisome outcome and treatment burden as the least worrisome outcome (conditional logit parameters: 3.19 (standard error 0.09) for stroke, 0 for treatment burden). None of the outcomes were always chosen as the most or least worrisome by more than 25% of respondents, indicating that all outcomes were somewhat worrisome to respondents. Predefined subgroup analyses according to age, self-reported life-expectancy, degree of comorbidity, number of medications and antihypertensive treatment did not reveal meaningful differences. CONCLUSIONS: Although some outcomes were more worrisome to patients than others, our results indicate that none of the outcomes should be disregarded for clinical practice guidelines and health economic assessments.

Net benefit of statins for primary prevention of cardiovascular disease in people 75 years or older: a benefit-harm balance modeling study.

BACKGROUND: We determined the risk thresholds above which statin use would be more likely to provide a net benefit for people over the age of 75 years without history of cardiovascular disease (CVD). METHODS: An exponential model was used to estimate the differences in expected benefit and harms in people treated with statins over a 10-year horizon versus not treated. The analysis was repeated 100,000 times to consider the statistical uncertainty and produce a distribution of the benefit-harm balance index from which we determined the 10-year CVD risk threshold where benefits outweighed the harms. We considered treatment estimates from trials and observational studies, baseline risks, patient preferences, and competing risks of non-CVD death, and statistical uncertainty. RESULTS: Based on average preferences, statins were more likely to provide a net benefit at a 10-year CVD risk of 24% and 25% for men aged 75-79 years and 80-84 years, respectively, and 21% for women in both age groups. However, these thresholds varied significantly depending on differences in individual patient preferences for the statin-related outcomes, with interquartile ranges of 21-33% and 23-36% for men aged 75-79 years and 80-84 years, respectively, as well as 20-32% and 21-32% for women aged 75-79 years and 80-84 years, respectively. CONCLUSIONS: Statins would more likely provide a net benefit for primary prevention in older people taking the average preferences if their CVD risk is well above 20%. However, the thresholds could be much higher or lower depending on preferences of individual patients, which suggests more emphasis should be placed on individual-based decision-making, instead of recommending statins for everyone based on a single or a small number of thresholds.

Utilization of modern contraceptives and predictors among women in Shimelba refugee camp, Northern Ethiopia.

Women living in refugee camps, in addition to the common hardships, such as drought, and famine, are also prone to another peculiar problem: an unintended pregnancy. The impact of unintended pregnancy is so severe that the rate of women who die or suffer an injury while giving birth in crisis settings is almost double the world average death rate. Thus, this study was aimed to investigate the utilization of modern contraceptive and associated factors among women in the reproductive age group in Shimelba refugee camp, Northern Ethiopia. A community-based cross-sectional study was employed and 329 study subjects were selected using simple random sampling technique with a face-to-face interview. The prevalence of using modern contraceptive was 47.7% and the study showed that being older [AOR = 0.017, 95%CI: 0.001, 0.467], being single [AOR = 0.17, 95%CI:0.031,0.914], being unemployed [AOR = 0.21, 95% CI:0.001,0.392], having no partner support [AOR = 0.006, 95% CI:0.001,0.044], and inconvenient service site AOR = 0.089,95% CI:0.013, 0.595] were factors that contributed to women not using modern contraceptive methods. Receipt of counseling on family planning utilization was more likely to helps women to use it [AOR = 3.37, 95% CI: 1.1095, 10.236]. Our study concluded that the current prevalence rate of contraceptive use is fairly good. However, much effort has to be made to improve this result. The situations in refugee can exacerbate the existing barriers to the use of contraceptives. Given its grave consequence on the livelihood of women, the contraceptive issue should be given due emphasis using several techniques including education to expand the awareness on modern contraceptive so as to augment access to family planning.

Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.

The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations. METHODS: We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes. RESULTS: In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile. CONCLUSIONS: All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A Modeling Study.

Background: Many guidelines use expected risk for cardiovascular disease (CVD) during the next 10 years as a basis for recommendations on use of statins for primary prevention of CVD. However, how harms were considered and weighed against benefits is often unclear. Objective: To identify the expected risk above which statins provide net benefit. Design: Quantitative benefit-harm balance modeling study. Data Sources: Network meta-analysis of primary prevention trials, a preference survey, and selected observational studies. Target Population: Persons aged 40 to 75 years with no history of CVD. Time Horizon: 10 years. Perspective: Clinicians and guideline developers. Intervention: Low- or moderate-dose statin versus no statin. Outcome Measures: The 10-year risk for CVD at which statins provide at least a 60% probability of net benefit, with baseline risk, frequencies of and preferences for statin benefits and harms, and competing risk for non-CVD death taken into account. Results of Base-Case Analysis: Younger men had net benefit at a lower 10-year risk for CVD than older men (14% for ages 40 to 44 years vs. 21% for ages 70 to 75 years). In women, the risk required for net benefit was higher (17% for ages 40 to 44 years vs. 22% for ages 70 to 75 years). Atorvastatin and rosuvastatin provided net benefit at lower 10-year risks than simvastatin and pravastatin. Results of Sensitivity Analysis: Most alternative assumptions led to similar findings. Limitation: Age-specific data for some harms were not available. Conclusion: Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risk at which net benefit occurs varies considerably by age, sex, and statin type. Primary Funding Source: Swiss Government Excellence Scholarship Office, Béatrice Ederer-Weber Foundation, and North-South Cooperation at the University of Zurich.

Should statin guidelines consider patient preferences? Eliciting preferences of benefit and harm outcomes of statins for primary prevention of cardiovascular disease in the sub-Saharan African and European contexts.

BACKGROUND: Patient preferences are key parameters to evaluate benefit-harm balance of statins for primary prevention but they are not readily available to guideline developers and decision makers. Our study aimed to elicit patient preferences for benefit and harm outcomes related to use of statins for primary cardiovascular disease prevention and to examine how the preferences differ across economically and socio-culturally different environments. METHODS: We conducted preference-eliciting surveys using best-worst scaling designed with a balanced incomplete-block design (BIBD) on 13 statins-related outcomes on 220 people in Ethiopia and Switzerland. The participants made tradeoff decisions and selected the most and least worrisome outcomes concurrently from each scenario generated using the BIBD. The design yielded 34,320 implied paired-comparisons and 2860 paired-responses as unit of analysis for eliciting the preferences that were analyzed using a conditional-logit model on a relative scale and surface under the cumulative ranking curve from multivariate random-effects meta-analysis model on a scale of 0 to 1. RESULTS: There was high internal consistency of responses and minimal amount of measurement error in both surveys. Severe stroke was the most worrisome outcome with a ceiling preference of 1 (on 0 to 1 scale) followed by severe myocardial infarction, 0.913 (95% CI, 0.889-0.943), and cancer, 0.846 (0.829-0.855); while treatment discontinuation, 0.090 (0.023-0.123), and nausea/headache, 0.060 (0.034-0.094) were the least worrisome outcomes. Preferences were similar between Ethiopia and Switzerland with overlapping uncertainty intervals and concordance correlation of 0.97 (0.90-0.99). CONCLUSIONS: Our study provides much needed empirical evidence on preferences that help clinical guidelines consider for weighing the benefit and harm outcomes when recommending for or against statins for primary prevention of cardiovascular disease. The preferences are consistent across the disparate settings; however, we recommend inclusion of more countries in future studies to ensure the generalizability of the preferences to all environments.

Quality of routine health data collected by health workers using smartphone at primary health care in Ethiopia.

BACKGROUND: Mobile phone based applications are considered by many as potentially useful for addressing challenges and improving the quality of data collection in developing countries. Yet very little evidence is available supporting or refuting the potential and widely perceived benefits on the use of electronic forms on smartphones for routine patient data collection by health workers at primary health care facilities. METHODS: A facility based cross sectional study using a structured paper checklist was prepared to assess the completeness and accuracy of 408 electronic records completed and submitted to a central database server using electronic forms on smartphones by 25 health workers. The 408 electronic records were selected randomly out of a total of 1772 maternal health records submitted by the health workers to the central database over a period of six months. Descriptive frequencies and percentages of data completeness and error rates were calculated. RESULTS: When compared to paper records, the use of electronic forms significantly improved data completeness by 209 (8%) entries. Of a total 2622 entries checked for completeness, 2602 (99.2%) electronic record entries were complete, while 2393 (91.3%) paper record entries were complete. A very small percentage of error rates, which was easily identifiable, occurred in both electronic and paper forms although the error rate in the electronic records was more than double that of paper records (2.8% vs. 1.1%). More than half of entry errors in the electronic records related to entering a text value. CONCLUSIONS: With minimal training, supervision, and no incentives, health care workers were able to use electronic forms for patient assessment and routine data collection appropriately and accurately with a very small error rate. Minimising the number of questions requiring text responses in electronic forms would be helpful in minimizing data errors.

Determinants of repeated abortion among women of reproductive age attending health facilities in Northern Ethiopia: a case-control study.

BACKGROUND: Every year, an estimated 19-20 million unsafe abortions take place, almost all in developing countries, leading to 68,000 deaths and millions more injured many permanently. Many women throughout the world, experience more than one abortion in their lifetimes. Repeat abortion is an indicator of the larger problem of unintended pregnancy. This study aimed to identify determinants of repeat abortion in Tigray Region, Ethiopia. METHODS: Unmatched case-control study was conducted in hospitals in Tigray Region, northern Ethiopia, from November 2014 to June 2015. The sample included 105 cases and 204 controls, recruited from among women seeking abortion care at public hospitals. Clients having two or more abortions ("repeat abortion") were taken as cases and those who had a total of one abortion were taken as controls ("single abortion"). Cases were selected consecutive based on proportional to size allocation while systematic sampling was employed for controls. Data were analyzed using SPSS version 20.0. Binary and multiple variable logistic regression analyses were calculated with 95% CI. RESULTS: Mean age of cases was 24 years (±6.85) and 22 years (±6.25) for controls. 79.0% of cases had their sexual debut in less than 18 years of age compared to 57% of controls. 42.2% of controls and 23.8% of cases cited rape as the reason for having an abortion. Study participants who did not understand their fertility cycle and when they were most likely to conceive after menstruation (adjusted odds ratio [AOR] = 2.0, 95% confidence interval [CI]: 1.1-3.7), having a previous abortion using medication (AOR = 3.3, CI: 1.83, 6.11), having multiple sexual partners in the preceding 12 months (AOR = 4.4, CI: 2.39,8.45), perceiving that the abortion procedure is not painful (AOR = 2.3, CI: 1.31,4.26), initiating sexual intercourse before the age of 18 years (AOR = 2.7, CI: 1.49, 5.23) and disclosure to a third-party about terminating the pregnancy (AOR = 2.1, CI: 1.2,3.83) were independent predictors of repeat abortion. CONCLUSION: This study identified several factors correlated with women having repeat abortions. It may be helpful for the Government of Ethiopia to encourage women to delay sexual debut and decrease their number of sexual partners, including by promoting discussion within families about sexuality, to decrease the occurrence of repeated abortion.