Considerations for legal, ethical, and effective practice in dementia research.

Dementia represents a potentially overwhelming health burden, both for the UK and worldwide. Addressing this fast-growing issue is a key priority for the government, health service and the public. Advances in care including the development of efficacious disease-modifying, and eventually curative, treatments can only be achieved through effective dementia research. Specifically, research directly involving participants with dementia is essential to further understanding. However, working with cognitively impaired participants with and without capacity to consent to research presents unique ethical and legal challenges. For clinicians and scientists on the frontline of dementia research, scenarios frequently arise that pose such challenges. A lack of guidance for a consistent approach in navigating these scenarios limits researchers' ability to proceed with confidence. This represents a threat to the rights and wishes of research participants as well as the field at large, as it may lead to studies being unnecessarily terminated or, worse, poor practice. In this article, we take a multiprofessional approach, informed by carer input, to these issues. We review the relevant ethical and legal literature relating to the conduct of non-interventional research studies in patients with dementia. This includes a thorough recap of the Mental Capacity Act (2005), which provides a legal framework in England and Wales for conducting research with participants who lack capacity to consent. We also discuss the important, but sometimes incomplete, role of research ethics committees in guiding researchers. We then present and discuss a series of case vignettes designed to highlight areas of incomplete coverage by existing governance. These vignettes describe theoretical scenarios informed by our own real-word experiences of encountering ethical issues when conducting dementia research. They include scenarios in which participants demonstrate varying degrees of understanding of the research they are involved in and ability to communicate their wishes and feelings. Building on these vignettes, we then provide a checklist for researchers to work through when presented with similar scenarios. This checklist covers the key ethical, legal and practical considerations that we have argued for. Taken together, this article can act as a guide, previously lacking in the literature, for colleagues in the field to enable much needed ethical, legal and effective research.

Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood.

An accurate diagnosis of neurodegenerative disease and traumatic brain injury is important for prognostication and treatment. Neurofilament light and glial fibrillary acidic protein (GFAP) are leading biomarkers for neurodegeneration and glial activation that are detectable in blood. Yet, current recommendations require rapid centrifugation and ultra-low temperature storage post-venepuncture. Here, we investigated if these markers can be accurately measured in finger-prick blood using dried plasma spot cards. Fifty patients (46 with dementia; 4 with traumatic brain injury) and 19 healthy volunteers underwent finger-prick and venous sampling using dried plasma spot cards and aligned plasma sampling. Neurofilament light and GFAP were quantified using a Single molecule array assay and correlations between plasma and dried plasma spot cards assessed. Biomarker concentrations in plasma and finger-prick dried plasma spot samples were significantly positively correlated (neurofilament light ρ = 0.57; GFAP ρ = 0.58, P < 0.001). Finger-prick neurofilament light and GFAP were significantly elevated after acute traumatic brain injury with non-significant group-level increases in dementia (91% having Alzheimer's disease dementia). In conclusion, we present preliminary evidence that quantifying GFAP and neurofilament light using finger-prick blood collection is viable, with samples stored at room temperature using dried plasma spot cards. This has potential to expand and promote equitable testing access, including in settings where trained personnel are unavailable to perform venepuncture.

Cost-Effectiveness of an Intensive Upper Limb Rehabilitation Therapy for Children With Unilateral Cerebral Palsy: An Economic Evaluation of a Randomized Controlled Trial.

Background: Unilateral cerebral palsy is a major cause of childhood disability and a substantial economic burden. Intensive group-based therapy, consisting of hybrid constraint-induced movement and bimanual therapies, has been shown to be effective in improving specific quality-of-life domains in children with this disability. Our objective in this study was to assess if this intervention was cost-effective compared with standard care. Methods: An open-label, parallel, randomized controlled trial with an embedded economic evaluation of the intervention was conducted. A total of 47 children were randomized to either the intervention group (n = 27) or the standard care (n = 20) group. The effectiveness of the intervention was assessed using the Cerebral Palsy Quality of Life (Child) questionnaire across several domains. Nonparametric bootstrapping was used to quantify uncertainty intervals (UIs) for incremental cost-effectiveness ratios. Results: The incremental cost-effectiveness ratios for the intervention were 273(95107 to 945)forPainandImpactofDisability,1071 (95% UI: -5718to4606) for Family Health and 1732(956448 to 8775)forAccesstoServices.Forthe4remainingdomains,theinterventionwasdominatedbystandardcare.Atawillingness-to-paythresholdof1000, only for the Pain and Impact of Disability domain was the intervention likely to have a probability of being cost-effective exceeding 0.75. Conclusions: Other than the Pain and Impact of Disability domain, there was insufficient evidence demonstrating the intervention to be cost-effective over a 13-week time horizon.

Implementation of a Mentoring Program for Mentee-Mentor Satisfaction: A Longitudinal Pilot Study.

Introduction: Mentoring is a unique educational workplace relationship that can support both the mentee and mentor's skill, knowledge, social, and emotional needs. The primary aim of this longitudinal pilot study was to implement a formal mentoring program to assess its effect on mentee and mentor satisfaction. Methods: Data was collected from two hospitals in New South Wales, Australia in late 2018 and early 2019. Junior doctors (mentees) and senior medical staff (mentors) were asked to complete pre-, mid-, and oost-program surveys, with questions relevant to mentee-mentor satisfaction, interactions, and participation. Mixed-effects ordinal logistic regression models were used to assess the program effect on mentee-mentor satisfaction, while Fishers' exact test was used to evaluate mentee-mentor interactions and participation. Results: Although there was evidence of upwards trends in the proportion of mentees and mentors who reported their satisfaction in the program as excellent and rated their work satisfaction as being very influenced by the program, both trends were statistically non-significant. While our study was likely underpowered, high participation rates provide promising evidence of the program's acceptability and feasibility. Conclusion: Though not reaching statistical significance, study results suggest that the implementation of a mentoring program has the potential to increase satisfaction levels among its participants, be they mentees or mentors. It is recommended that future studies recruit larger samples thereby having sufficient statistical power. Furthermore, causality should be explored in more detail through a multi-site randomized controlled trial design.

Population incidence and associated mortality of urinary tract infection in people living with dementia.

OBJECTIVES: Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. METHODS: Data were extracted for n = 2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. RESULTS: UTIs in dementia (HR=2.18, 95 %CI [1.88-2.53], p < .0) and diabetes (1.21[1.01-1.45], p = .035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p < .0) compared to matched individuals with neither dementia nor diabetes. 5.4 % of untreated PLWD died within 60 days of GP diagnosis-increasing to 5.9 % in PLWD with diabetes. CONCLUSIONS: Incidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.

Scabies prevalence after ivermectin-based mass drug administration for lymphatic filariasis, Samoa 2018-2019.

BACKGROUND: Scabies is a common skin infestation caused by the Sarcoptes scabei mite. Ivermectin, one of three drugs used in mass drug administration (MDA) for lymphatic filariasis, is also effective for treating scabies. Ivermectin-based MDA was first conducted in Samoa in August 2018, with ivermectin being offered to those aged ≥5 years. Here, we report scabies prevalence in Samoa after MDA. METHODS: We conducted household surveys 1.5-3.5 months (Survey 1) and 6-8 months (Survey 2) after the 2018 MDA in 35 primary sampling units. We conducted clinical examination for scabies-like rash and used International Alliance for the Control of Scabies classification criteria. We estimated scabies prevalence by age, gender and region. Multivariable logistic regression was used to assess factors associated with prevalence. RESULTS: We surveyed 2868 people (499 households) and 2796 people (544 households) aged 0-75 years in Surveys 1 and 2, respectively. Scabies prevalence increased from 2.4% (95% CI 2.1-2.7%) to 4.4% (95% CI 4.0-4.9%) between surveys. Scabies was associated with younger age (0-4 years: aOR 3.5 [2.9-4.2]; 5-15 years: aOR 1.6 [1.4-1.8] compared to ≥16 years), female gender (aOR 1.2 [95% CI 1.1-1.4]; region (aOR range from 1.4 [1.1-1.7] to 2.5 [2.1-3.1] between regions), large households (aOR 2.6 [2.0-3.4] households ≥13), and not taking MDA in 2018 (aOR 1.3 [95% CI 1.1-1.6]). CONCLUSIONS: We found moderate prevalence of scabies in two population-representative surveys conducted within 8 months of the 2018 MDA for lymphatic filariasis. Prevalence appeared to increase between the surveys, and ongoing surveillance is recommended, particularly in young children.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Background: Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. Methods: This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients' performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). Findings: The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r = 0.86, p < 0.001 and r = 0.81, p = 0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555) = 3.99; p < 0.001). Interpretation: Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. Funding: This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH (II-LB-0715-20006).

Remote Monitoring of Physiology in People Living With Dementia: An Observational Cohort Study.

BACKGROUND: Internet of Things (IoT) technology enables physiological measurements to be recorded at home from people living with dementia and monitored remotely. However, measurements from people with dementia in this context have not been previously studied. We report on the distribution of physiological measurements from 82 people with dementia over approximately 2 years. OBJECTIVE: Our objective was to characterize the physiology of people with dementia when measured in the context of their own homes. We also wanted to explore the possible use of an alerts-based system for detecting health deterioration and discuss the potential applications and limitations of this kind of system. METHODS: We performed a longitudinal community-based cohort study of people with dementia using "Minder," our IoT remote monitoring platform. All people with dementia received a blood pressure machine for systolic and diastolic blood pressure, a pulse oximeter measuring oxygen saturation and heart rate, body weight scales, and a thermometer, and were asked to use each device once a day at any time. Timings, distributions, and abnormalities in measurements were examined, including the rate of significant abnormalities ("alerts") defined by various standardized criteria. We used our own study criteria for alerts and compared them with the National Early Warning Score 2 criteria. RESULTS: A total of 82 people with dementia, with a mean age of 80.4 (SD 7.8) years, recorded 147,203 measurements over 958,000 participant-hours. The median percentage of days when any participant took any measurements (ie, any device) was 56.2% (IQR 33.2%-83.7%, range 2.3%-100%). Reassuringly, engagement of people with dementia with the system did not wane with time, reflected in there being no change in the weekly number of measurements with respect to time (1-sample t-test on slopes of linear fit, P=.45). A total of 45% of people with dementia met criteria for hypertension. People with dementia with α-synuclein-related dementia had lower systolic blood pressure; 30% had clinically significant weight loss. Depending on the criteria used, 3.03%-9.46% of measurements generated alerts, at 0.066-0.233 per day per person with dementia. We also report 4 case studies, highlighting the potential benefits and challenges of remote physiological monitoring in people with dementia. These include case studies of people with dementia developing acute infections and one of a person with dementia developing symptomatic bradycardia while taking donepezil. CONCLUSIONS: We present findings from a study of the physiology of people with dementia recorded remotely on a large scale. People with dementia and their carers showed acceptable compliance throughout, supporting the feasibility of the system. Our findings inform the development of technologies, care pathways, and policies for IoT-based remote monitoring. We show how IoT-based monitoring could improve the management of acute and chronic comorbidities in this clinically vulnerable group. Future randomized trials are required to establish if a system like this has measurable long-term benefits on health and quality of life outcomes.

Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis.

BACKGROUND: Dysfunction of the locus coeruleus-noradrenergic system occurs early in Alzheimer's disease, contributing to cognitive and neuropsychiatric symptoms in some patients. This system offers a potential therapeutic target, although noradrenergic treatments are not currently used in clinical practice. OBJECTIVE: To assess the efficacy of drugs with principally noradrenergic action in improving cognitive and neuropsychiatric symptoms in Alzheimer's disease. METHODS: The MEDLINE, Embase and ClinicalTrials.gov databases were searched from 1980 to December 2021. We generated pooled estimates using random effects meta-analyses. RESULTS: We included 19 randomised controlled trials (1811 patients), of which six were judged as 'good' quality, seven as 'fair' and six 'poor'. Meta-analysis of 10 of these studies (1300 patients) showed a significant small positive effect of noradrenergic drugs on global cognition, measured using the Mini-Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale (standardised mean difference (SMD): 0.14, 95% CI: 0.03 to 0.25, p=0.01; I2=0%). No significant effect was seen on measures of attention (SMD: 0.01, 95% CI: -0.17 to 0.19, p=0.91; I2=0). The apathy meta-analysis included eight trials (425 patients) and detected a large positive effect of noradrenergic drugs (SMD: 0.45, 95% CI: 0.16 to 0.73, p=0.002; I2=58%). This positive effect was still present following removal of outliers to account for heterogeneity across studies. DISCUSSION: Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer's disease for general cognition and apathy. However, several factors should be considered before designing future clinical trials. These include targeting of appropriate patient subgroups and understanding the dose effects of individual drugs and their interactions with other treatments to minimise risks and maximise therapeutic effects. PROSPERO REGISTERATION NUMBER: CRD42021277500.

Corrigendum to Ng MS, Malacova E, Hurst C, David MC, Johnson DW, Mallett AJ. "Clinical Outcomes of People With Fabry Disease - ANZDATA Registry Study." Kidney Int Rep. 2021;6:2481-2485.

[This corrects the article DOI: 10.1016/j.ekir.2021.06.013.].

Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: Reducing 'number needed to test' by targeting older age groups, hotspots, and household members of infected persons.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission.

Ezetimibe: Use, costs, and adverse events in Australia.

AIM: To analyze the subsidized use and reported adverse events of ezetimibe, used to lower cholesterol, in Australia over the 11 years following its inclusion on the Pharmaceutical Benefits Scheme (PBS) in 2004. METHODS: Pharmacoepidemiological analysis of dispensed prescriptions from Medicare Australia. Adverse event data were obtained from the Therapeutic Goods Administration. Use was measured by the defined daily dose (DDD) per 1000 population per day for each calendar year. Adverse events were counted by organ class system. RESULTS: Total ezetimibe use rose to 8.46 DDD/1000 population/d in the 11 years to 2015. Ezetimibe as a sole active ingredient was the most commonly dispensed formulation followed by the two combination products containing ezetimibe and 40 mg or 80 mg simvastatin. The average yearly increase in utilization was 19% with a 24% annual increase in costs to government (2006-2015) to $169.0 million in 2015. There were substantial differences in ezetimibe use between states, with no relationship to deaths from ischaemic heart disease (IHD) in each jurisdiction. The major reported adverse events were musculoskeletal and connective tissue disorders and gastrointestinal disorders. CONCLUSIONS: Ezetimibe use has increased rapidly in Australia since receiving public subsidy. Although the indications for subsidy are very restricted, there appears to have been widespread use, not explained by differential geographical IHD death rates. Latest guidelines still question the value of ezetimibe, so further discussion about whether the public spending on this medication for any potential improvement in population health outcomes is justified.

Risk assessment of student performance in the International Foundations of Medicine Clinical Science Examination by the use of statistical modeling.

PURPOSE: The primary aim of this study was to assess the predictive validity of cumulative grade point average (GPA) for performance in the International Foundations of Medicine (IFOM) Clinical Science Examination (CSE). A secondary aim was to develop a strategy for identifying students at risk of performing poorly in the IFOM CSE as determined by the National Board of Medical Examiners' International Standard of Competence. METHODS: Final year medical students from an Australian university medical school took the IFOM CSE as a formative assessment. Measures included overall IFOM CSE score as the dependent variable, cumulative GPA as the predictor, and the factors age, gender, year of enrollment, international or domestic status of student, and language spoken at home as covariates. Multivariable linear regression was used to measure predictor and covariate effects. Optimal thresholds of risk assessment were based on receiver-operating characteristic (ROC) curves. RESULTS: Cumulative GPA (nonstandardized regression coefficient [B]: 81.83; 95% confidence interval [CI]: 68.13 to 95.53) and international status (B: -37.40; 95% CI: -57.85 to -16.96) from 427 students were found to be statistically associated with increased IFOM CSE performance. Cumulative GPAs of 5.30 (area under ROC [AROC]: 0.77; 95% CI: 0.72 to 0.82) and 4.90 (AROC: 0.72; 95% CI: 0.66 to 0.78) were identified as being thresholds of significant risk for domestic and international students, respectively. CONCLUSION: Using cumulative GPA as a predictor of IFOM CSE performance and accommodating for differences in international status, it is possible to identify students who are at risk of failing to satisfy the National Board of Medical Examiners' International Standard of Competence.

The tolerability of a combined hepatitis A and typhoid vaccine in children aged 2-16 years: an observational study.

BACKGROUND: Combined hepatitis A and typhoid vaccines have been widely used globally and proven to be safe, well tolerated and efficacious in adults. The combined hepatitis A and typhoid vaccine (Vivaxim) available in Australia is licenced for use from age 16 years but the monovalent components are approved for use from age 2 years. Advantages of a single injection have led to widespread 'off-label' use of Vivaxim in children. This study aimed to investigate the tolerability of Vivaxim in children aged 2-16 years. METHODS: A prospective observational study was conducted at Travel Medicine Alliance clinics across Australia. Children who required vaccination for both hepatitis A and typhoid were offered the option of receiving Vivaxim. Parents were contacted 3 days post-vaccination and asked to respond to a questionnaire on adverse events following immunization (AEFIs). Reactions to Vivaxim were compared with reported reactions to the monovalent vaccines. RESULTS: Our study included 425 children who received Vivaxim, including 189 (44.5%) who received other vaccines on the same day. No serious AEFIs were reported, and 26.8% did not experience any side effects. In children who did not receive other vaccines in the same arm as Vivaxim (n = 325), most common local reactions were sore arm (70.5%), redness (16.0%) and swelling (11.1%). Reports of local AEFIs in our subjects was significantly more common than those reported for the individual monovalent vaccines. In children who did not receive other vaccines on the same day (n = 236), the most common systemic reactions were tiredness/lethargy/malaise (5.9%), headache (4.2%), fever (3.4%) and sore muscles and joints (3.4%). Fever was more common in children aged <6 years. Less than 5% of children reported missing school, sport or other regular activities. CONCLUSIONS: Vivaxim was well tolerated in children aged 2-16 years. Parents should be advised about AEFIs to Vivaxim so that they can make informed decisions about vaccination options.

High-Volume Surgeons Deliver Larger Surgical Margins in Oral Cavity Cancer.

PURPOSE: In oral cavity cancer surgery there are many factors that contribute to the surgical margin; thus, the factors determining patient outcomes are still not completely understood. The aim of this study was to determine which variable or variables had the greatest influence on increasing the size of the surgical margin. MATERIALS AND METHODS: A retrospective cohort study was conducted at the Royal Brisbane and Women's Hospital of patients who underwent resective surgery for a primary oral cavity cancer from January 1, 2008 through December 31, 2012. The primary outcome variable was the surgical margin, defined as the closest distance between the surgical edge and invasive cancer. A heterogeneous set of predictor variables was identified as potentially affecting the primary outcome variable: demographic, 5 surgical, and 7 histologic variables. The data then underwent statistical analysis using univariable linear regression, and variables that were found to have a statistical association were retained in a non-interaction multivariable model. RESULTS: This study included 250 patients. The results showed that high-volume surgeons delivered larger surgical margins than low-volume surgeons. The single most important variable associated with larger surgical margins was who performed the resective operation. The following variables also were associated with smaller surgical margins: retromolar trigone location, non-squamous cell carcinomas, perineural invasion, and a lip-split mandibulectomy surgical approach. CONCLUSION: There was a strong association between high-volume surgeons and larger surgical margins, supporting the rationalization of oral cavity cancer management in high-volume centers and by high-volume surgeons.

Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.

Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living <100m from a major river (OR 1.41), pigs in the community (OR 1.54), high cattle density in the district (OR 1.04 per head/sqkm), and high maximum rainfall in the wettest month (OR 1.003 per mm). Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.

A systematic review and meta-analysis of management options for adults who respond poorly to hepatitis B vaccination.

An estimated 5-10% of adults do not seroconvert after a three-dose primary course of hepatitis B vaccines, and are considered non-responders. Many approaches have been used to induce immunity in healthy adult non-responders, but few studies have compared their relative effectiveness. We conducted a systematic review and meta-analysis of seroconversion rates after additional doses of four approaches: 20 mcg or 40 mcg intramuscular (IM), and 5 mcg or 20 mcg intradermal (ID). The search identified 13 articles encompassing 16 studies (N=1067) that met the eligibility criteria. Seroconversion rates after additional doses of each approach were pooled and estimated. After one additional dose, the four approaches produced very similar seroconversion rates and we did not find any evidence to support the use of 40 mcg IM in healthy adults.

Meta-analysis of randomized controlled trials supports the use of incentives for inducing response to electronic health surveys.

OBJECTIVES: The objective of this meta-analysis was to assess incentive effectiveness on response to electronic health surveys. STUDY DESIGN AND SETTING: A systematic literature search of PubMed, Web of Science, CINAHL, EMBASE, and the Cochrane Library was performed from 1970 to March 2013. Two authors independently selected the trials, assessed methodological quality, and extracted data. Original authors were contacted for the missing information. RESULTS: The search strategy yielded nine trials (including 29,463 participants in total) that met eligibility criteria. For each of the incentive strategies examined, a random-effects model was used because of significant heterogeneity, and results were summarized as pooled odds ratios (ORs). Compared with no incentive, the offer of an incentive was seen to have a beneficial effect on response (OR, 1.48; 95% CI: 1.29, 1.71). Specifically, the odds of response were more than doubled when a monetary incentive was used (OR, 2.43; 95% CI: 1.60, 3.69) and increased when nonmonetary incentives were used (OR, 1.33; 95% CI: 1.17, 1.51). CONCLUSION: These findings indicate that health researchers using electronic surveys can improve the quality of their research by offering incentives to potential participants.

Assessing bias in a prospective study of diabetes that implemented substitution sampling as a recruitment strategy.

OBJECTIVE: Strategies such as reminders are frequently used to maximize baseline recruitment and for this reason are collectively termed "usual practice." The objective of this study was to investigate substitution sampling as an alternative recruitment strategy. STUDY DESIGN AND SETTINGS: Data are from the Living with Diabetes Study, which is a prospective cohort study providing a comprehensive examination of health care utilization. Baseline information was collected for 3,197 of 11,470 eligible individuals between November 2008 and October 2009. Follow-up occurred 12 months after recruitment, with outcome of interest being emergency department attendance. Biases resulting from the two recruitment programs were investigated through the comparison of adjusted logistic regression coefficients and absolute relative biases (ARBs). RESULTS: Corresponding estimates resulting from both programs were similar except for age (75+ years). This effect was significant (ß: -0.59; 95% confidence interval [CI]: -1.04, -0.13) under substitution sampling, but not under "usual practice" (ß: -0.36; 95% CI: -0.78, 0.07). Analysis using the ARB metric reinforced similarity, with the Wilcoxon signed-rank test failing to detect significant difference between programs (median difference: -1.01; 95% CI: -5.88, 2.02). CONCLUSION: Substitution sampling deserves consideration as a recruitment option alongside "usual practice," as concerns about additional bias may be unwarranted.

Risk of attrition in a longitudinal study of skin cancer: logistic and survival models can give different results.

OBJECTIVES: Longitudinal studies are a major tool for public health research, but their value can be undermined by attrition. Identification of factors associated with attrition through modeling depends on the efficient use of data and is conditional on modeling assumptions being met. The primary aim of this study was to compare the performance of four models in analyzing attrition risk. STUDY DESIGN AND SETTING: Data from participants who were lost to follow-up from The Nambour Skin Cancer Study between 1992 and 2000 were analyzed using logistic and survival models, for all-cause and nondeath attritions. RESULTS: During follow-up, 321 (19.8%) of 1,621 participants were lost to follow-up; 70 (4.3%) because of death and 251 (15.5%) for other reasons. Using survival models showed skin cancer diagnosis to be associated with increased all-cause attrition (hazard ratio: 2.3; 95% confidence interval [95% CI]: 1.5, 3.4) and nondeath attrition (subhazard ratio: 1.9; 95% CI: 1.0, 3.3). Using logistic regression resulted in inverse associations being observed for both all-cause attrition (odds ratio [OR]: 0.7; 95% CI: 0.5, 1.1) and nondeath attrition (OR: 0.5; 95% CI: 0.3, 1.0). CONCLUSION: These results demonstrate the relative inadequacy of a logistic as opposed to a survival approach when analyzing attrition risk in the presence of time-varying covariates and multiple timepoints.