Are cash incentives always king? A randomized controlled trial evaluating hedonic versus cash incentives (TEH-C).

Introduction: Physical inactivity is a risk factor for obesity and non-communicable diseases. Despite myriad health and non-health benefits resulting from physical activity (PA), most individuals do not meet PA recommendations. Providing an incentive for meeting activity goals may increase activity levels. Classical economists argue that cash is the best incentive. Behavioral economists have posited that hedonic (pleasurable) incentives (e.g., massages, restaurant meals) may be superior to cash when incentives are offered over multiple time periods. To date, no studies have directly compared the effectiveness of cash versus hedonic incentives in promoting PA across multiple time periods. Methods: We conducted a two-arm, parallel, 4-month randomized controlled trial with healthy adults in Singapore where participants were randomized to either cash or hedonic incentives. Participants could earn up to SGD50 (≈USD37) in cash or hedonic incentives each month they met the study's step target of 10,000 steps daily on at least 20/25 days out of the first 28 days of a month. The primary objective was to compare the mean proportion of months that participants met the step target between the two arms. Results: By month 4, participants in the cash (N = 154) and hedonic incentive (N = 156) arms increased their mean daily steps by 870 (p < 0.001) and 1,000 steps (p < 0.001), respectively. The mean proportion of months the step target was achieved was 90.53 and 88.34 for participants in the cash and hedonic incentive arms respectively, but differences across arms were small and not statistically significant for this or any outcome assessed. Conclusion: Our findings suggest that both cash and hedonic incentives are effective at promoting physical activity but that neither strategy is clearly superior.Clinical trial registration: ClinicalTrials.gov, NCT04618757 registered on November 6, 2020.

Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Investigating 5-Level EQ-5D (EQ-5D-5L) Values Based on Preferences of Patients With Heart Disease.

OBJECTIVES: Several studies have shown that patients with heart disease value hypothetical health states differently from the general population. We aimed to investigate the health preferences of patients with heart disease and develop a value set for the 5-level EQ-5D (EQ-5D-5L) based on these patient preferences. METHODS: Patients with confirmed heart disease were recruited from 2 hospitals in Singapore. A total of 86 EQ-5D-5L health states (10 per patient) were valued using a composite time trade-off method according to the international valuation protocol for EQ-5D-5L; 20-parameter linear models and 8-parameter cross-attribute level effects models with and without an N45 term (indicating whether any health state dimension at level 4 or 5 existed) were estimated. Each model included patient-specific random intercepts. Model performance was evaluated for out-of-sample and in-sample predictive accuracy in terms of root mean square error. The discriminative ability of the utility values was assessed using heart disease-related functional classes. RESULTS: A total of 576 patients were included in the analysis. The preferred model, with the lowest out-of-sample root mean square error, was a 20-parameter linear model including N45. Predicted utility values ranged from -0.727 for the worst state to 1 for full health; the value for the second-best state was 0.981. Utility values demonstrated good discriminative ability in differentiating among patients of varied functional classes. CONCLUSIONS: An EQ-5D-5L value set representing the preferences of patients with heart disease was developed. The value set could be used for patient-centric economic evaluation and health-related quality of life assessment for patients with heart disease.

Budget impact and cost-effectiveness analyses of the COBRA-BPS multicomponent hypertension management programme in rural communities in Bangladesh, Pakistan, and Sri Lanka.

BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. METHODS: In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. FINDINGS: Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh, $10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were $0·63 for Bangladesh, $0·29 for Pakistan, and $1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh, $2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. INTERPRETATION: The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. FUNDING: The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust.

A Community-Based Intervention for Managing Hypertension in Rural South Asia.

BACKGROUND: The burden of hypertension is escalating, and control rates are poor in low- and middle-income countries. Cardiovascular mortality is high in rural areas. METHODS: We conducted a cluster-randomized, controlled trial in rural districts in Bangladesh, Pakistan, and Sri Lanka. A total of 30 communities were randomly assigned to either a multicomponent intervention (intervention group) or usual care (control group). The intervention involved home visits by trained government community health workers for blood-pressure monitoring and counseling, training of physicians, and care coordination in the public sector. A total of 2645 adults with hypertension were enrolled. The primary outcome was reduction in systolic blood pressure at 24 months. Follow-up at 24 months was completed for more than 90% of the participants. RESULTS: At baseline, the mean systolic blood pressure was 146.7 mm Hg in the intervention group and 144.7 mm Hg in the control group. At 24 months, the mean systolic blood pressure fell by 9.0 mm Hg in the intervention group and by 3.9 mm Hg in the control group; the mean reduction was 5.2 mm Hg greater with the intervention (95% confidence interval [CI], 3.2 to 7.1; P<0.001). The mean reduction in diastolic blood pressure was 2.8 mm Hg greater in the intervention group than in the control group (95% CI, 1.7 to 3.9). Blood-pressure control (<140/90 mm Hg) was achieved in 53.2% of the participants in the intervention group, as compared with 43.7% of those in the control group (relative risk, 1.22; 95% CI, 1.10 to 1.35). All-cause mortality was 2.9% in the intervention group and 4.3% in the control group. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, a multicomponent intervention that was centered on proactive home visits by trained government community health workers who were linked with existing public health care infrastructure led to a greater reduction in blood pressure than usual care among adults with hypertension. (Funded by the Joint Global Health Trials scheme; COBRA-BPS ClinicalTrials.gov number, NCT02657746.).

A vision 'bolt-on' increases the responsiveness of EQ-5D: preliminary evidence from a study of cataract surgery.

OBJECTIVES: (1) To evaluate the effect of adding a vision dimension ('bolt-on') to the 5-level EQ-5D (EQ-5D-5L) and 3-level EQ-5D (EQ-5D-3L) on their responsiveness, and (2) to compare the responsiveness of a vision 'bolt-on' EQ-5D-3L (EQ-5D-3L + V) with SF-6D and Health Utilities Index Mark 3 (HUI3) to the benefit of cataract surgery. METHODS: Sixty-three patients were assessed before and after their cataract surgery using the EQ-5D-3L, EQ-5D-5L, SF-6D, HUI3, as well as a 3-level and a 5-level vision dimension. Preference-based indices were calculated using available value sets for EQ-5D-3L, EQ-5D-3L + V, EQ-5D-5L, SF-6D, and HUI3, and non-preference-based indices were calculated using the sum-score method for EQ-5D-5L and EQ-5D-5L + V (vision bolt-on EQ-5D-5L). Responsiveness was assessed using the standardized response mean (SRM) and F-statistic. RESULTS: Among preference-based indices, mean changes from pre to post-surgery in EQ-5D-3L + V and EQ-5D-3L indices were 0.031 and 0.018, respectively. The mean changes for EQ-5D-5L, SF-6D and HUI3 indices were 0.020, 0.012 and 0.105, respectively. The SRM (F-statistic) for EQ-5D-3L + V and EQ-5D-3L indices were 0.458 (13.2) and 0.098 (0.6), respectively. The responsiveness of EQ-5D-3L + V was better than EQ-5D-5L, SF-6D; the responsiveness of HUI3 was better than all other measures. Using non-preference-based indices, mean change for EQ-5D-5L + V and EQ-5D-5L were 0.067 and 0.017, respectively. The corresponding SRM (F-statistic) were 0.709 (31.7) and 0.295 (5.4). CONCLUSIONS: Preliminary evidence from our study suggests that a vision 'bolt-on' may increase the responsiveness of EQ-5D-3L and EQ-5D-5L to change in health outcomes experienced by patients undergoing cataract surgery. In absence of the preference-based vision bolt-on EQ-5D-5L index, HUI3 was the most responsive measure.

TRIal to slow the Progression Of Diabetes (TRIPOD): study protocol for a randomized controlled trial using wireless technology and incentives.

BACKGROUND: The outcomes for those with type 2 diabetes mellitus (T2DM) in Singapore are poor. In this TRIal to slow the Progression Of Diabetes (TRIPOD), we will evaluate the effectiveness and cost-effectiveness of a comprehensive diabetes management package (DMP), with or without a financial incentives program, M-POWER Rewards, in efforts to improve HbA1c levels for individuals with T2DM. METHODS/DESIGN: TRIPOD is a randomized, open-label, controlled, multi-center, superiority trial with three parallel arms: (1) usual care only, (2) usual care with DMP, and (3) usual care with DMP plus M-POWER Rewards. A total of 339 adults with sub-optimally controlled T2DM (self-reported HbA1c 7.5-11.0%) will be block randomized according to a 1:1:1 allocation ratio to the three arms. The primary outcome is mean change in HbA1c level at Month 12 from baseline. Secondary outcomes include mean change in HbA1c level at Months 6, 18, and 24; mean changes at Months 6, 12, 18, and 24 in weight, blood pressure, and self-reported physical activity, weight monitoring, blood glucose monitoring, medication adherence, diabetes self-management, sleep quality, work productivity and daily activity impairment, and health utility index; and proportion of participants initiating insulin treatment by Months 6, 12, 18, and 24. Incremental cost-effectiveness ratios will be computed based on costs per improvement in HbA1c at Month 12 and converted to cost per quality-adjusted life year gained. DISCUSSION: The TRIPOD study will present insights about the long-term cost-effectiveness and financial viability of the interventions and the potential for integrating within usual care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03800680. Registered on 11 January 2019.

Validity and Utility of the Center for Epidemiological Studies Depression Scale for Detecting Depression in Family Caregivers of Persons with Dementia.

BACKGROUND/AIMS: The psychometric properties of Center for Epidemiological Studies Depression Scale (CES-D) have never been substantively investigated in caregivers of persons with dementia (PwD). We evaluated the validity and reliability of CES-D for detecting caregiver depression in dementia, and assessed whether CES-D could provide added utility beyond Zarit Burden Interview (ZBI). METHOD: Family caregivers of community-dwelling PwD (n = 394) completed self-administered questionnaires containing CES-D. Factorial validity was evaluated with confirmatory factor analysis; convergent and discriminant validity with Pearson's correlation coefficient; known-group validity by comparing across key variables; and internal consistency reliability with Cronbach's α. Cohen's κ was used to compare the agreement between those with depression (CES-D ≥16) and those with high caregiver burden (ZBI >60). RESULTS: CES-D demonstrated convergent, discriminant and known-group validity, consistent with a priori hypotheses. The original four-factor model of CES-D produced the best model-fit indices. Internal consistency reliability was good for the CES-D total scale (α = 0.92), but lower for the Positive affect and Interpersonal problems subscales (α = 0.70-0.74). Forty-five percent of the caregivers had depression as identified by CES-D (95% CI 40-50%), but most of them were not identified by high ZBI scores (κ = 0.16). CONCLUSIONS: CES-D is a valid and reliable scale for detecting caregiver depression in dementia. It has added utility, beyond that of a caregiver burden scale, in identifying a subgroup of caregivers with depression but not burden. However, two subscales (Positive affect and Interpersonal problems) may require caution in interpretation among non-Caucasian caregivers.

EQ-5D-5L is More Responsive than EQ-5D-3L to Treatment Benefit of Cataract Surgery.

BACKGROUND: It is not clear whether 5-level EQ-5D (EQ-5D-5L) utilities based on recently developed value sets are more responsive than 3-level EQ-5D (EQ-5D-3L) utilities. OBJECTIVES: The study aims were to compare (1) the responsiveness of EQ-5D-5L and EQ-5D-3L utilities and (2) the responsiveness of these utilities with the Short Form-6 Dimension (SF-6D) and Health Utilities Index Mark 3 (HUI3) utilities to the treatment benefit of cataract surgery. METHODS: A total of 148 patients were interviewed before and after their cataract surgery using EQ-5D-3L, EQ-5D-5L, SF-6D, and HUI3. Responsiveness was assessed for all measures using the mean change (post-treatment-pre-treatment), standardized effect size (SES), standardized response mean (SRM), and F-statistic. RESULTS: Using the Singapore value sets, mean change for EQ-5D-3L and EQ-5D-5L utilities was 0.016 and 0.028, SES was 0.097 and 0.199; SRM was 0.091 and 0.196; and F-statistic was 1.2 and 5.7, respectively. Similar trends were observed using the UK/England EQ-5D value sets, although the magnitude was slightly smaller. The mean change, SES, SRM and F-statistics for SF-6D (UK value set) were 0.020, 0.234, 0.249, and 9.2, respectively. The values of mean change, SES, SRM and F-statistics for HUI3 (Canada value set) were 0.080, 0.472, 0.474, and 33.3, respectively. CONCLUSIONS: The EQ-5D-5L utilities tend to be more responsive than the EQ-5D-3L utilities to treatment benefits of cataract surgery. The HUI3 utilities are more responsive than both the EQ-5D-5L and SF-6D, and SF-6D utilities may be slightly more responsive than the EQ-5D-5L for assessing patients undergoing cataract surgery.

Valuation of EQ-5D-5L health states: a comparison of seven Asian populations.

Objectives: To compare the time trade-off (TTO) utility values of EQ-5D-5L health states elicited from different general populations in Asia. Methods: We analyzed the TTO data from seven Asian EQ-5D-5L valuation studies in which utility values of 86 EQ-5D-5L health states were elicited from general population samples. An eight-parameter multiplicative regression model including five dimension parameters (mobility [MO], self-care, usual activities [UA], pain/discomfort, anxiety/depression) and three level parameters (level 2 [L2], level 3 [L3], and level 4 [L4]) was used to model the data from each of the populations. The model coefficients were compared to understand how the valuations of EQ-5D-5L health states differ. Results: For dimension parameters, Korea and Indonesia generally had the highest and lowest values among the populations, respectively; UA and MO commonly had the highest and lowest values among the parameters, respectively. For level parameters, Singapore and Korea generally had the highest and lowest values, respectively; L2 showed less variance compared to L3 and L4. Koreans, Indonesians, and Singaporeans appeared to have different health preferences compared with other populations. Conclusion: Utility values of EQ-5D-5L health states differ among Asian populations, suggesting that each health system should establish and use its own value set.

Sample size determination for EQ-5D-5L value set studies.

PURPOSE: The EuroQol 5-Dimension (EQ-5D) is a widely used health status instrument for cost-utility analysis of healthcare interventions. Recently, its 5-Level version (EQ-5D-5L) and a protocol for conducting valuation of its health states were developed. We propose four approaches for estimating the sample size for EQ-5D-5L valuation according to the standardized procedures of the protocol. METHODS: The first approach is for estimating mean health state utility values with a desired precision level using a regression model. The second approach, empirical in nature, determines a sample size based on mean absolute error in predicting health state values using a large-scale reference study. The last two approaches are for assessing the significance of regression coefficients of health state descriptors and to estimate the regression coefficients with a desired precision for predicting health state utility values. RESULTS: Using data from a Singaporean study, we estimated parameters that are useful for sample size determination, including the design effect. Each of the approaches was illustrated with examples and pragmatic recommendations were provided. CONCLUSIONS: Capitalizing on the EQ-5D-5L valuation protocol, we proposed four sample size estimation approaches which can help to decide an appropriate sample size for a value set study.

Multicomponent intervention versus usual care for management of hypertension in rural Bangladesh, Pakistan and Sri Lanka: study protocol for a cluster randomized controlled trial.

BACKGROUND: High blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension continues to be a significant public health issue with sub-optimal BP control rates. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering BP among adults with hypertension in rural communities in Bangladesh, Pakistan and Sri Lanka. METHODS/DESIGN: This study is a stratified, cluster randomized controlled trial with a qualitative component for evaluation of processes and stakeholder feedback. The MCI has five components: (1) home health education by government community health workers (CHWs), (2) BP monitoring and stepped-up referral to a trained general practitioner using a checklist, (3) training public and private providers in management of hypertension and using a checklist, (4) designating hypertension triage counter and hypertension care coordinators in government clinics and (5) a financing model to compensate for additional health services and provide subsidies to low income individuals with poorly controlled hypertension. Usual care will comprise existing services in the community without any additional training. The trial will be conducted on 2550 individuals aged ≥40 years with hypertension (with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, based on the mean of the last two of three measurements from two separate days, or on antihypertensive therapy) in 30 rural communities in Bangladesh, Pakistan and Sri Lanka. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability-adjusted life years averted will be computed. Stakeholders including policy makers, provincial- and district-level coordinators of relevant programmes, physicians, CHWs, key community leaders, hypertensive individuals and family members in the identified clusters will be interviewed. DISCUSSION: The study will provide evidence of the effectiveness and cost-effectiveness of MCI strategies for BP control compared to usual care in the rural public health infrastructure in South Asian countries. If shown to be successful, MCI may be a long-term sustainable strategy for tackling the rising rates of CVD in low resourced countries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02657746 . Registered on 14 January 2016.

Do chronic disease patients value generic health states differently from individuals with no chronic disease? A case of a multicultural Asian population.

BACKGROUND: There is conflicting evidence as to whether patients with chronic disease value hypothetical health states differently from individuals who have not experienced any long-lasting diseases. Furthermore, most studies regarding this issue have been conducted in western countries, with only one conducted in Asia. We aimed to evaluate possible systematic differences in the valuation of EuroQol Group five dimensions 3-level (EQ-5D-3L) health states by chronic disease patients and a population with no chronic disease in Singapore. METHODS: A face-to-face survey for the valuation of the 42 health states of the EQ-5D-3L using the visual analogue scale (VAS) method was conducted in Singapore. The survey also asked participants to report any chronic diseases they had. Ordinary least-square regression models were employed to assess possible differences in the valuation scores of all health states, severe health states and non-severe health states by individual chronic disease patient groups (diabetes, rheumatism, hypertension, heart diseases and lung diseases) and by a group of participants with no chronic disease. A difference of 4 to 8 points on the 100-point VAS was considered to be of practical significance. RESULTS: The analysis included 332 participants with at least one chronic disease and 651 participants with no chronic disease. After taking health state descriptors and covariates into account, mean valuation scores of the 42 health states by the heart disease group were higher by 4.6 points (p-value = 0.032) compared to the no chronic disease group. Specifically, the heart disease group valued severe health states 5.4 points higher (p-value = 0.025) than the no chronic disease group. There was no practically significant difference in the mean valuation score of non-severe health states between the heart disease group and the no chronic disease group. No practically significant differences were found in the mean valuation score of all health states, severe health states and non-severe health states between any other chronic disease group and the no chronic disease group. CONCLUSIONS: In Singapore, heart disease patients valued EQ-5D-3L severe health states differently from individuals with no chronic disease. Other chronic disease groups did not value EQ-5D-3L health states differently from the no chronic disease group.

How is the most severe health state being valued by the general population?

BACKGROUND: It has been reported that valuation of health states that are close to death, such as the most severe health state, can be affected by health state valuation procedure, and their utility values are difficult to predict. We examined how the most severe health states of Short Form-6 dimension (SF-6D) and EuroQoL-5 dimension-3 level (EQ-5D-3L) were valued by the Singapore general population. METHODS: Overall, 249 SF-6D and 42 EQ-5D-3L states were valued by two separate samples from the Singapore general population using the visual analogue scale (VAS) method. Ordinary least-square regression model was employed to explain deficit in the valuation of the most severe state using the health state descriptors. RESULTS: A total of 1021 participants from the SF-6D sample and 1015 participants from the EQ-5D-3L sample were included in the analysis. We observed that 67% of the SF-6D participants and 74% of the EQ-5D-3L participants considered the most severe state worse than dead. The most severe state had mean VAS valuation scores more than 20-25 points lower than the adjacent states that are better by only one level in only one dimension. SF-6D VAS valuation score for the most severe state was 27 points and 12 points lower than expected according to the health state descriptors among the participants who considered the most severe state worse than dead and better than dead, respectively. Similar results were found for the EQ-5D-3L valuation. CONCLUSIONS: The most severe health state was valued lower than expected according to its descriptors.

Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial.

BACKGROUND: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. METHODS/DESIGN: The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. DISCUSSION: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. TRIAL REGISTRATION: Clinical trials gov NCT01723150.

Racial differences among patients undergoing laparoscopic gastric bypass surgery: a population-based trend analysis from 2002 to 2008.

BACKGROUND: Laparoscopic gastric bypass surgery (LGBS) has become the most widely used bariatric procedure due to its beneficial long-term outcomes for patients with morbid obesity. However, it is unclear whether racial differences in admission for LGBS have changed over time compared to racial differences in all other admissions. We aimed to investigate the trends and differences in the use of LGBS among white, African-American, and Hispanic patients from 2002 to 2008. METHODS: We performed a secondary analysis of data on obese adult patients operated between 2002 and 2008, using the Nationwide Inpatient Sample (NIS) database. The probability of being admitted for LGBS was estimated using logistic regression with race, year, and year by race interaction as predictors, controlling for numerous patient and hospital characteristics. RESULTS: Among 1,704,972 obese hospitalized patients captured through NIS from 2002 to 2008, 2.6 % underwent LGBS (2.8 % Whites, 1.7 % African-Americans, and 2.6 % Hispanics). In adjusted analysis, obese African-American (OR 0.48, p < 0.001) and Hispanic patients (OR 0.59, p < 0.001) were less likely to be admitted for LGBS than white patients in 2002. Race-year interactions showed that the odds of African-Americans undergoing LGBS significantly increased from 2002 to 2008 compared with Whites (annual OR 1.03, p < 0.001) while no such increase was detected for Hispanics (annual OR 1.02, p = 0.11). In 2008, African-American (OR 0.58, p < 0.001) and Hispanic patients (OR 0.65, p < 0.001) still had lower odds than white patients. CONCLUSIONS: This is the first study showing that the difference in the use of LGBS between obese African-American and white patients declined between 2002 and 2008. However, LGBS use still remained significantly lower for both African-American and Hispanic patients in 2008 compared with white patients.

A Bayesian approach for inference from a bridging study with binary outcomes.

To address concerns that ethnic differences in any clinical trial may affect the performance of a treatment, separate clinical trials may be required for different regions. If a drug is approved in one region based on a bigger clinical trial, a bridging study with smaller size may be conducted in a new region to evaluate the similarity of the earlier clinical data to the new population. This article applies a Bayesian strategy to combine a bridging study with reference studies to assess treatment effect similarity for binary endpoints. The methods have been illustrated with a numerical example using Markov-chain Monte Carlo (MCMC) techniques.

Hyperbaric oxygen therapy in necrotising soft tissue infections: a study of patients in the United States Nationwide Inpatient Sample.

PURPOSE: Necrotising soft tissue infection (NSTI) is a deadly disease associated with a significant risk of mortality and long-term disability from limb and tissue loss. The aim of this study was to determine the effect of hyperbaric oxygen (HBO(2)) therapy on mortality, complication rate, discharge status/location, hospital length of stay and inflation-adjusted hospitalisation cost in patients with NSTI. METHODS: This was a retrospective study of 45,913 patients in the Nationwide Inpatient Sample (NIS) from 1988 to 2009. RESULTS: A total of 405 patients received HBO(2) therapy. The patients with NSTI who received HBO(2) therapy had a lower mortality (4.5 vs. 9.4 %, p = 0.001). After adjusting for predictors and confounders, patients who received HBO(2) therapy had a statistically significantly lower risk of dying (odds ratio (OR) 0.49, 95 % confidence interval (CI) 0.29-0.83), higher hospitalisation cost (US$52,205 vs. US$45,464, p = 0.02) and longer length of stay (LOS) (14.3 days vs. 10.7 days, p < 0.001). CONCLUSIONS: This retrospective analysis of HBO(2) therapy in NSTI showed that despite the higher hospitalisation cost and longer length of stay, the statistically significant reduction in mortality supports the use of HBO(2) therapy in NSTI.

Do insurance and race represent independent predictors of undergoing total shoulder arthroplasty? A secondary data analysis of 3529 patients.

HYPOTHESIS: Race and insurance status are independent predictors of the choice between total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) of the shoulder joint. BACKGROUND: Current literature shows that ethnic and socioeconomic status may influence access to health care. However, no study has demonstrated whether insurance status and race are independent predictors that patients with glenohumeral osteoarthritis will undergo TSA. MATERIALS AND METHODS: Patients with primary International Classification of Diseases, 9th revision, Clinical Modification, procedure codes for TSA and HA were selected from the 1988 to 2007 United States Nationwide Inpatient Sample. Primary predictors were race (Caucasian, African American, Hispanic, other) and insurance status (private, Medicare, Medicaid, other). Multiple logistic regressions were used to determine whether insurance status and race were associated with the choice of procedure for patients presenting with glenohumeral osteoarthritis. RESULTS: The study included data for 3529 patients, of whom 2369 underwent TSA (67.1%) and the remaining 1160 (32.9%) underwent HA. Of patients treated using TSA, 29% were privately insured, 63.2% had Medicare, and 2.5% had Medicaid (P < .001), and 62.1% were Caucasian, 2.5% were African American, 2.46% were Hispanic, and 30.9% had other ethnicities (P < .001). DISCUSSION: Multiple logistic regression analysis found that privately insured patients and Medicare patients did not show statistically different odds of having TSA compared with patients within the Medicaid (reference category) or "other payment" categories, after adjustment for a variety of potential confounders. Caucasian patients also did not show statistically different chances of undergoing TSA compared with African Americans. CONCLUSIONS: We were unable to support statistical evidence that race and insurance status are independent factors associated with the choice of the surgical procedure in patients with glenohumeral osteoarthritis.

Height gain during early childhood is an important predictor of schooling and mathematics ability outcomes.

AIM: To examine the association between height gain at different stages of early childhood and schooling and cognitive outcomes in 12-year-old Malawian children. METHODS: A prospective cohort study looking at the growth and development of 325 rural Malawian children. Main outcome measures were highest school grade completed, number of times repeating grades and percentage of correctly answered mathematical questions at 12 years of age. Height-for-age at 1 month and conditional height gain for 6, 18 and 60 months were used as predictors. Ordinal logistic and linear regression analyses were used to estimate the association and adjust for confounder. RESULTS: The conditional height gain during 18-60 months was positively associated with mathematics test results (p=0.003) and negatively associated with number of times repeating grades (p=0.011). It was not significantly associated with highest grade completed (p=0.194) if those who never attended school were included as having completed zero grade, but was positively (p=0.049) associated with this outcome among those who ever attended school. CONCLUSION: Height gain during the 18-60 months period of age was related to schooling and mathematics ability at age 12 years. The importance of promoting catch-up growth after the period when stunting is common should receive attention.