Information nudges for influenza vaccination: Evidence from a large-scale cluster-randomized controlled trial in Finland

BackgroundVaccination is the most effective means of preventing the spread of infectious diseases. Despite the proven benefits of vaccination, vaccine hesitancy keeps many people from getting vaccinated.Methods and findingsWe conducted a large-scale cluster randomized controlled trial in Finland to test the effectiveness of centralized written reminders (distributed via mail) on influenza vaccination coverage. The study included the entire older adult population (aged 65 years and above) in 2 culturally and geographically distinct regions with historically low (31.8%, n = 7,398, mean age 75.5 years) and high (57.7%, n = 40,727, mean age 74.0 years) influenza vaccination coverage. The study population was randomized into 3 treatments: (i) no reminder (only in the region with low vaccination coverage); (ii) an individual-benefits reminder, informing recipients about the individual benefits of vaccination; and (iii) an individual- and social-benefits reminder, informing recipients about the additional social benefits of vaccination in the form of herd immunity. There was no control treatment group in the region with high vaccination coverage as general reminders had been sent in previous years. The primary endpoint was a record of influenza vaccination in the Finnish National Vaccination Register during a 5-month follow-up period (from October 18, 2018 to March 18, 2019). Vaccination coverage after the intervention in the region with historically low coverage was 41.8% in the individual-benefits treatment, 38.9% in the individual- and social-benefits treatment and 34.0% in the control treatment group. Vaccination coverage after the intervention in the region with historically high coverage was 59.0% in the individual-benefits treatment and 59.2% in the individual- and social-benefits treatment. The effect of receiving any type of reminder letter in comparison to control treatment group (no reminder) was 6.4 percentage points (95% CI: 3.6 to 9.1, p < 0.001). The effect of reminders was particularly large among individuals with no prior influenza vaccination (8.8 pp, 95% CI: 6.5 to 11.1, p < 0.001). There was a substantial positive effect (5.3 pp, 95% CI: 2.8 to 7.8, p < 0.001) among the most consistently unvaccinated individuals who had not received any type of vaccine during the 9 years prior to the study. There was no difference in influenza vaccination coverage between the individual-benefit reminder and the individual- and social-benefit reminder (region with low vaccination coverage: 2.9 pp, 95% CI: −0.4 to 6.1, p = 0.087, region with high vaccination coverage: 0.2 pp, 95% CI: −1.0 to 1.3, p = 0.724). Study limitations included potential contamination between the treatments due to information spillovers and the lack of control treatment group in the region with high vaccination coverage.ConclusionsIn this study, we found that sending reminders was an effective and scalable intervention strategy to increase vaccination coverage in an older adult population with low vaccination coverage. Communicating the social benefits of vaccinations, in addition to individual benefits, did not enhance vaccination coverage. The effectiveness of letter reminders about the benefits of vaccination to improve influenza vaccination coverage may depend on the prior vaccination history of the population.Trial registrationAEA RCT registry AEARCTR-0003520 and ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03748160","term_id":"NCT03748160"}}NCT03748160

Lauri Sääksvuori and co-workers study the benefits of reminders in an influenza vaccination program in Finland.     

Risk factors for ocular infection with Chlamydia trachomatis in children 6 months following mass treatment in Tanzania

Background

Trachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass treatment with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the infectious reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in children post-mass treatment.

Methodology

All children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and household characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection detected by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic regression model was used, accounting for household clustering of children for analysis.

Principal Findings

Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40–4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25–0.80). The age group 2–4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household.

Conclusions

While one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is not sufficient to eliminate infection. Findings that young children (ages 2–4 years) and households with increasing numbers of infected and untreated children have a positive association with infection at 6 months suggest that such households could be targeted for more intensive follow up.     

Concordance of ompA types in children re-infected with ocular Chlamydia trachomatis following mass azithromycin treatment for trachoma

BackgroundThe chlamydial major outer membrane protein, encoded by the ompA gene, is a primary target for chlamydial vaccine research. However, human studies of ompA-specific immunity are limited, and prior studies have been limited in differentiating re-infection from persistent infection. The purpose of this study was to assess whether children living in trachoma-endemic communities with re-infections of ocular chlamydia were more likely to be infected with a different or similar genovar.Methodology and findingsThe study included 21 communities from a trachoma-hyperendemic area of Ethiopia that had been treated with a mass azithromycin distribution for trachoma. Conjunctival swabbing was offered to all children younger than 5 years of age at baseline (i.e., pre-treatment), and then at follow-up visits 2 and 6 months later. Swabs were subjected to polymerase chain reaction (PCR) to detect C. trachomatis. A random sample of 359 PCR-positive swabs, stratified by study visit and study community, was chosen for ompA sequencing. In addition, ompA sequencing was performed on all swabs of 24 children who experienced chlamydial re-infection (i.e., positive chlamydial test before treatment, negative test 2 months following mass distribution of azithromycin, and again a positive test 6 months post-treatment). ompA sequencing was successful for 351 of 359 swabs of the random sample and 44 of 48 swabs of the re-infection sample. In the random sample, ompA types clustered within households more than would be expected by chance. Among the 21 re-infected children with complete ompA data, 14 had the same ompA type before and after treatment.ConclusionThe high frequency of ompA concordance suggests incomplete genovar-specific protective immunity and the need for multiple antigens as vaccine targets.     

Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine

Sexually transmitted Chlamydia trachomatis infections are a serious public-health problem. With more than 90 million new cases occurring annually, C. trachomatis is the most common cause of bacterial sexually transmitted disease worldwide. Recent progress in elucidating the immunobiology of Chlamydia muridarum infection of mice has helped to guide the interpretation of immunological findings in studies of human C. trachomatis infection and has led to the development of a common model of immunity. In this review, we describe our current understanding of the immune response to infection with Chlamydia spp. and how this information is improving the prospects for development of a vaccine against infection with C. trachomatis.     

Prevalence of and risk factors for trachoma in Kano state, Nigeria

Background

In northern Nigeria, trachoma is an important public health problem, but there are currently few population-based data on prevalence of disease and no formal trachoma control programs.

Methodology / Principal Findings

In Kano state, Nigeria, we conducted a population-based cross-sectional survey using multistage cluster random sampling, combining examination for clinical signs of trachoma and application of questionnaires assessing potential household-level risk factors. A total of 4491 people were examined in 40 clusters, of whom 1572 were aged 1–9 years, and 2407 (53.6%) were female. In 1–9 year-olds, the prevalence of trachomatous inflammation–follicular (TF) was 17.5% (95% CI: 15.7–19.5%). In a multivariate model, independent risk factors for active trachoma were the presence of flies on the face (OR 1.98, 95% CI 1.30–3.02); a dirty face (OR 2.45, 95% CI 1.85–3.25) and presence of animal dung within the compound of residence (OR 3.46, 95% CI 1.62–7.41). The prevalence of trachomatous trichiasis in persons aged ≥15years was 10.9% (95% CI: 9.7–12.2%). Trichiasis was significantly more common in adult females than in adult males.

Conclusion/Significance

There is an urgent need for a trachoma control program in Kano state, with emphasis given to provision of good quality trichiasis surgery. Particular effort will need to be made to identify women with trichiasis and engage them with appropriate services while also taking steps to secure azithromycin for mass treatment and ensuring personal and environmental hygiene.     

Chlamydia trachomatis: identification of susceptibility markers for ocular and sexually transmitted infection by immunogenetics

The aim of this review is to present a concise overview of all data available on the immunogenetics of Chlamydia trachomatis infections, both sexually transmitted urogenital and ocular infections. Currently, candidate gene approaches are used to identify genes related to the susceptibility to and severity of C. trachomatis infections. The main focus in the review will be on data obtained by the study of human cohorts.     

Azithromycin mass treatment for trachoma control: risk factors for non-participation of children in two treatment rounds

Background

Persistent non-participation of children in mass drug administration (MDAs) for trachoma may reduce program impact. Risk factors that identify families where participation is a problem or program characteristics that foster non-participation are poorly understood. We examined risk factors for households with at least one child who did not participate in two MDAs compared to households where all children participated in both MDAs.

Methods/Principal Findings

We conducted a case control study in 28 Tanzanian communities. Cases included all 152 households with at least one child who did not participate in the 2008 and 2009 MDAs with azithromycin. Controls consisted of a random sample of 460 households where all children participated in both MDAs. A questionnaire was asked of all families. Random-intercept logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), control for clustering, and adjust for community size. In total, 140 case households and 452 control households were included in the analyses. Compared to controls, guardians in case households had higher odds of reporting excellent health (OR 4.12 (CI 95% 1.57–10.86)), reporting a burden due to family health (OR 3.15 (95% CI 1.35–7.35)), reduced ability to rely on others for assistance (OR 1.66 (95% CI 1.01–2.75)), being in a two (versus five) days distribution program (OR 3.31 (95% CI 1.68–6.50)) and living in a community with <2 community treatment assistants (CTAs)/1000 residents (OR 2.07 (95% CI 1.04–4.12). Furthermore, case households were more likely to have more children, younger guardians, unfamiliarity with CTAs, and CTAs with more travel time to their assigned households (p-values<0.05).

Conclusions/Significance

Compared to full participation households, households with persistent non-participation had a higher burden of familial responsibility and seemed less connected in the community. Additional distribution days and lessening CTAs'' travel time to their furthest assigned households may prevent non-participation.     

Environmental risk factors for Cryptosporidium infection in an island from Western Venezuela

Few investigations have been conducted on risk factors for Cryptosporidium infection in communities from developing countries. A study was conducted to determine the prevalence and risk factors for cryptosporidiosis in San Carlos island, Venezuela. A sample of 515 subjects (mean age +/- SD: 21.4 +/- 17.8 years) was surveyed. Single fecal specimens were collected and modified Ziehl-Neelsen carbolfuchsin staining of formalin-ether concentrate stools were examined for identification of the parasite. Infections with Cryptosporidium (67 of 515, 13%) were common. Prevalence of the parasite varied among sectors of the community; 34 of 67(50.7%) cases of cryptosporidiosis clustered in two sectors with extreme poverty. Variables strongly associated with a higher risk for the infection (p < 0.01) were residing in these sectors versus the remainder, living in a hut or small residence versus a brick or larger house, using an area of backyard rather than a toilet or latrine for defecation, and having contact with soil contaminated with human feces. Crowding was also a risk (p < 0.05). Contact with human feces contaminated-soil may be an important mode of transmission and poverty a predisposing factor for the infection.     

Trachoma prevalence and associated risk factors in the gambia and Tanzania: baseline results of a cluster randomised controlled trial

Background

Blinding trachoma, caused by ocular infection with Chlamydia trachomatis, is targeted for global elimination by 2020. Knowledge of risk factors can help target control interventions.

Methodology/Principal Findings

As part of a cluster randomised controlled trial, we assessed the baseline prevalence of, and risk factors for, active trachoma and ocular C. trachomatis infection in randomly selected children aged 0–5 years from 48 Gambian and 36 Tanzanian communities. Both children''s eyes were examined according to the World Health Organization (WHO) simplified grading system, and an ocular swab was taken from each child''s right eye and processed by Amplicor polymerase chain reaction to test for the presence of C. trachomatis DNA. Prevalence of active trachoma was 6.7% (335/5033) in The Gambia and 32.3% (1008/3122) in Tanzania. The countries'' corresponding Amplicor positive prevalences were 0.8% and 21.9%. After adjustment, risk factors for follicular trachoma (TF) in both countries were ocular or nasal discharge, a low level of household head education, and being aged ≥1 year. Additional risk factors in Tanzania were flies on the child''s face, being Amplicor positive, and crowding (the number of children per household). The risk factors for being Amplicor positive in Tanzania were similar to those for TF, with the exclusion of flies and crowding. In The Gambia, only ocular discharge was associated with being Amplicor positive.

Conclusions/Significance

These results indicate that although the prevalence of active trachoma and Amplicor positives were very different between the two countries, the risk factors for active trachoma were similar but those for being Amplicor positive were different. The lack of an association between being Amplicor positive and TF in The Gambia highlights the poor correlation between the presence of trachoma clinical signs and evidence of C. trachomatis infection in this setting. Only ocular discharge was associated with evidence of C. trachomatis DNA in The Gambia, suggesting that at this low endemicity, this may be the most important risk factor.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00792922","term_id":"NCT00792922"}}NCT00792922     

The cluster-randomized Quality Initiative in Rectal Cancer trial: evaluating a quality-improvement strategy in surgery

Background

Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of cancer. We tested whether a quality-improvement strategy to change surgical practice would improve these outcomes.

Methods

Sixteen hospitals were cluster-randomized to the intervention (Quality Initiative in Rectal Cancer strategy) or control (normal practice) arm. Consecutive patients with primary rectal cancer were accrued from May 2002 to December 2004. Surgeons at hospitals in the intervention arm could voluntarily participate by attending workshops, using opinion leaders, inviting a study team surgeon to demonstrate optimal techniques of total mesorectal excision, completing postoperative questionnaires, and receiving audits and feedback. Main outcome measures were hospital rates of permanent colostomy and local recurrence of cancer.

Results

A total of 56 surgeons (n = 558 patients) participated in the intervention arm and 49 surgeons (n = 457 patients) in the control arm. The median follow-up of patients was 3.6 years. In the intervention arm, 70% of surgeons participated in workshops, 70% in intraoperative demonstrations and 71% in postoperative questionnaires. Surgeons who had an intraoperative demonstration provided care to 86% of the patients in the intervention arm. The rates of permanent colostomy were 39% in the intervention arm and 41% in the control arm (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.63–1.48). The rates of local recurrence were 7% in the intervention arm and 6% in the control arm (OR 1.06, 95% CI 0.68–1.64).

Interpretation

Despite good participation by surgeons, the resource-intense quality-improvement strategy did not reduce hospital rates of permanent colostomy or local recurrence compared with usual practice. (ClinicalTrials.gov trial register no. {"type":"clinical-trial","attrs":{"text":"NCT00182130","term_id":"NCT00182130"}}NCT00182130.)Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of the cancer. Local recurrence is especially feared, because it is usually inoperable and patients can suffer a slow, painful death.¹ The use of total mesorectal excision, which involves dissection of the lymph node-bearing portion of the rectum,² has resulted in improved outcomes, with local recurrence rates as low as 1%–5% and rates of permanent colostomy of 10%–15%.^3–6 Population-based rates of local recurrence are unavailable for any North American jurisdiction, although a Canadian hospital series found that rates varied from 10% to 45% based on the practice volume and training of surgeons.⁷ A surgical report on health regions in the province of Ontario (population 13 million) found that rates of permanent colostomy varied from 31% to 41%.⁸ This geographic variation in outcomes, together with rates of inferior outcomes as compared to outcomes specific to total mesorectal excision, suggest that gaps exist in the quality of rectal surgery provided to patients with rectal cancer.Quality-improvement strategies for encouraging physicians to change practice include continuing medical education, the use of opinion leaders, and audit and feedback.^9–11 As well, improvement may be enhanced by using a participatory and supportive approach that focuses on the system and not on individual practitioners.^12,13 The small number of studies that have evaluated changes in surgeons’ practices often have targeted process measures, such as preoperative ordering of antibiotics, rather than patient outcomes, such as recurrence of cancer.^14,15We tested whether use of a surgeon-directed quality-improvement strategy would improve hospital rates of permanent colostomy and local recurrence of cancer among patients undergoing surgery for rectal cancer. We used the Quality Initiative in Rectal Cancer (QIRC) strategy, which integrates quality-improvement interventions and principles to encourage surgeons to provide optimal total mesorectal excision to patients with rectal cancer.¹⁶     

Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n = 419) and control (n = 914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and egg count ratio (ECR) to compare the prevalence of STH eggs and arithmetic and geometric mean egg counts for STH eggs per gram of soil in the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. In the control arm, the arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR = 0.98 (95% CI: 0.91, 1.05)) or mean egg counts (ECR = 0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces.Trial Registration:{"type":"clinical-trial","attrs":{"text":"NCT01590095","term_id":"NCT01590095"}}NCT01590095.     

Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial

Background

It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities.

Methods and Findings

In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1–10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%–13.3%) at month 12, significantly lower than the treated group (p<0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%–4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year.

Conclusions

This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization''s trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.

Trial registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00322972","term_id":"NCT00322972"}}NCT00322972 Please see later in the article for the Editors'' Summary     

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

ABSTRACT: BACKGROUND: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. METHODS: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). DISCUSSION: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment.     

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background

Delirium occurs frequently in elderly hospitalised patients and is associated with higher mortality, increased length of hospital stay, functional decline, and admission to long-term care. Healthcare professionals frequently do not recognise delirium, indicating that education can play an important role in improving delirium care for hospitalised elderly. Previous studies have indicated that e-learning can provide an effective way of educating healthcare professionals and improving quality of care, though results are inconsistent.

Methods and design

This stepped wedge cluster randomised trial will assess the effects of a complementary delirium e-learning course on the implementation of quality improvement initiative, which aims to enhance the recognition and management of delirium in elderly patients. The trial will be conducted in 18 Dutch hospitals and last 11 months. Measurements will be taken in all participating wards using monthly record reviews, in order to monitor delivered care. These measurements will include the percentage of elderly patients who were screened for the risk of developing delirium, use of the Delirium Observation Screening scale, use of nursing or medical interventions, and the percentage of elderly patients who were diagnosed with delirium. Data regarding the e-learning course will be gathered as well. These data will include user characteristics, information regarding use of the course, delirium knowledge before and after using the course, and the attitude and intentions of nurses concerning delirium care.

Setting

The study will be conducted in internal medicine and surgical wards of eighteen hospitals that are at the beginning stages of implementing the Frail Elderly Project in the Netherlands.

Discussion

Better recognition of elderly patients at risk for delirium and subsequent care is expected from the introduction of an e-learning course for nurses that is complementary to an existing quality improvement project. This trial has the potential to demonstrate that e-learning can be a vital part of the implementation process, especially for quality improvement projects aimed at complex health issues such as delirium. The study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.

Trial registration

Netherlands Trial Register (NTR): NTR2885     

Improving stroke prevention therapy for patients with atrial fibrillation in primary care: protocol for a pragmatic,cluster-randomized trial

Background

The prevalence of atrial fibrillation (AF) is growing as the population ages, and at least 15% of ischemic strokes are attributed to AF. However, many high-risk AF patients are not offered guideline-recommended stroke prevention therapy due to a variety of system, provider, and patient-level barriers.

Methods

We will conduct a pragmatic, cluster-randomized controlled trial randomizing primary care clinics to test a “toolkit” of quality improvement interventions in primary care. In keeping with the recommendations of the chronic care model to simultaneously activate patients and facilitate proactive care by providers, the toolkit includes provider-focused strategies (education, audit and feedback, electronic decision support, and reminders) plus patient-directed strategies (educational letters and reminders). The trial will include two feedback cycles at baseline and approximately 6 months and a final data collection at approximately 12 months. The study will be powered to show a difference of 10% in the primary outcome of proportion of patients receiving guideline-recommended stroke prevention therapy. Analysis will follow the intention-to-treat principle and will be blind to treatment allocation. Unit of analysis will be the patient; models will use generalized estimating equations to account for clustering at the clinical level.

Discussion

Stroke prevention therapy using anticoagulation in patients with AF is known to reduce strokes by two thirds or more in clinical trials, but most studies indicate under-use of this treatment in real-world practice. If the toolkit successfully improves care for patients with AF, stakeholders will be engaged to facilitate broader application to maximize the potential to improve patient outcomes. The intervention toolkit tested in this project could also provide a model to improve quality of care for other chronic cardiovascular conditions managed in primary care.

Trial registration

ClinicalTrials.gov (NCT01927445). Registered August 14, 2014 at https://clinicaltrials.gov/.

     

Serology,infection, and clinical trachoma as tools in prevalence surveys for re-emergence of trachoma in a formerly hyperendemic district

BackgroundTo eliminate trachoma as a public health problem, countries must achieve a district-level prevalence of trachomatous inflammation—follicular (TF) <5% in children ages 1–9 years. Re-emergence of TF could trigger additional rounds of mass drug/antibiotic administration (MDA), so accurate tools for use in surveys assessing trachoma prevalence are essential.Methodology & principal findingsWe surveyed 2401 children ages 1–9 years from 50 villages in Kongwa, Tanzania, 2 years post-MDA and 1.5 years after an impact survey found TF <5% in the same villages. Our survey included multiple tools: clinical determination of TF, Cepheid testing for Chlamydia trachomatis infection, and testing for anti-pgp3 antibodies via multiplex bead array. Photographs of the upper tarsal conjunctiva were taken in a subset of children to corroborate the field grades.Overall TF prevalence in 1–9 year olds was 7.1% (95% CI: 5.6%-8.9%), which decreased with age (p = <0.0001). TF prevalence by village was heterogeneous, with 19 villages having TF <5% and 16 villages having TF >10%. There was a strong correlation between field and photo grading of TF (kappa = 0.69; 95% CI: 0.60–0.78) and between TF and infection, with 21.5% of TF-positive children also testing positive for infection, as compared to only 1.6% of TF-negative children (p = 0.0010). Overall seroprevalence was 18.2% (95% CI: 14.8%-22.1%), which increased with age (p = <0.0001). Notably, 1–2 year olds, who were born after the cessation of MDA and theoretically should not have had exposure to C. trachomatis in the absence of transmission, had an average seroprevalence of 6.7%.Conclusions & significanceField TF prevalence, supported by photographic review and infection data, suggested re-emergence of trachoma in Kongwa. Moreover, seropositivity in the children born after cessation of MDA indicated exposure to C. trachomatis despite a previous survey finding of TF <5%. Examining seropositivity in specific age groups expected to have limited exposure to C. trachomatis can be used to detect re-emergence.     

Individual and occupational risk factors for knee osteoarthritis: results of a case-control study in Germany

Introduction

A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The distinction between work-related and other factors is crucial in assessing the risk and in deriving preventive measures in occupational health.

Methods

In a case-control study, patients with and without symptomatic knee osteoarthritis (OA) were questioned by means of a standardised questionnaire complemented by a semi-standardised interview. Controls were matched and assigned to the cases by gender and age. Conditional logistic regression was used in analysing data.

Results

In total, 739 cases and 571 controls were included in the study. In women and men, several individual and occupational predictors for knee OA could be described: obesity (odds ratio (OR) up to 17.65 in women and up to 12.56 in men); kneeling/squatting (women, OR 2.52 (>8,934 hours/life); men, 2.16 (574 to 12,244 hours/life), 2.47 (>12,244 hours/life)); genetic predisposition (women, OR 2.17; men, OR 2.37); and sports with a risk of unapparent trauma (women, OR 2.47 (≥1,440 hours/life); men, 2.58 (≥3,232 hours/life)). In women, malalignment of the knee (OR 11.54), pain in the knee already in childhood (OR 2.08), and the daily lifting and carrying of loads (≥1,088 tons/life, OR 2.13) were related to an increased OR; sitting and smoking led to a reduced OR.

Conclusions

The results support a dose-response relationship between kneeling/squatting and symptomatic knee OA in men and, for the first time, in women. The results concerning general and occupational predictors for knee OA reflect the findings from the literature quite well. Yet occupational risks such as jumping or climbing stairs/ladders, as discussed in the literature, did not correlate with symptomatic knee OA in the present study. With regards to occupational health, prevention measures should focus on the reduction of kneeling activities and the lifting and carrying of loads as well as general risk factors, most notably the reduction of obesity. More intervention studies of the effectiveness of tools and working methods for reducing knee straining activities are needed.     

Risk factors for pre-treatment mortality among HIV-infected children in rural Zambia: a cohort study

Background

Many HIV-infected children in sub-Saharan Africa enter care at a late stage of disease. As preparation of the child and family for antiretroviral therapy (ART) can take several clinic visits, some children die prior to ART initiation. This study was undertaken to determine mortality rates and clinical predictors of mortality during the period prior to ART initiation.

Methods

A prospective cohort study of HIV-infected treatment-naïve children was conducted between September 2007 and September 2010 at the HIV clinic at Macha Hospital in rural Southern Province, Zambia. HIV-infected children younger than 16 years of age who were treatment-naïve at study enrollment were eligible for analysis. Mortality rates prior to ART initiation were calculated and risk factors for mortality were evaluated.

Results

351 children were included in the study, of whom 210 (59.8%) were eligible for ART at study enrollment. Among children ineligible for ART at enrollment, 6 children died (mortality rate: 0.33; 95% CI:0.15, 0.74). Among children eligible at enrollment, 21 children died before initiation of ART and their mortality rate (2.73 per 100 person-years; 95% CI:1.78, 4.18) was significantly higher than among children ineligible for ART (incidence rate ratio: 8.20; 95% CI:3.20, 24.83). In both groups, mortality was highest in the first three months of follow-up. Factors associated with mortality included younger age, anemia and lower weight-for-age z-score at study enrollment.

Conclusions

These results underscore the need to increase efforts to identify HIV-infected children at an earlier age and stage of disease progression so they can enroll in HIV care and treatment programs prior to becoming eligible for ART and these deaths can be prevented.     

Prevalence of trachoma in unity state, South Sudan: results from a large-scale population-based survey and potential implications for further surveys

Background

Large parts of South Sudan are thought to be trachoma-endemic but baseline data are limited. This study aimed to estimate prevalence for planning trachoma interventions in Unity State, to identify risk factors and to investigate the effect of different sampling approaches on study conclusions.

Methods and Findings

The survey area was defined as one domain of eight counties in Unity State. Across the area, 40 clusters (villages) were randomly selected proportional to the county population size in a population-based prevalence survey. The simplified grading scheme was used to classify clinical signs of trachoma. The unadjusted prevalence of trachoma inflammation-follicular (TF) in children aged 1–9 years was 70.5% (95% CI: 68.6–72.3). After adjusting for age, sex, county and clustering of cases at household and village level the prevalence was 71.0% (95% CI: 69.9–72.1). The prevalence of trachomatous trichiasis (TT) in adults was 15.1% (95% CI: 13.4–17.0) and 13.5% (95% CI: 12.0–15.1) before and after adjustment, respectively. We estimate that 700,000 people (the entire population of Unity State) require antibiotic treatment and approximately 54,178 people require TT surgery. Risk factor analyses confirmed child-level associations with TF and highlighted that older adults living in poverty are at higher risk of TT. Conditional simulations, testing the alternatives of sampling 20 or 60 villages over the same area, indicated that sampling of only 20 villages would have provided an acceptable level of precision for state-level prevalence estimation to inform intervention decisions in this hyperendemic setting.

Conclusion

Trachoma poses an enormous burden on the population of Unity State. Comprehensive control is urgently required to avoid preventable blindness and should be initiated across the state now. In other parts of South Sudan suspected to be highly trachoma endemic, counties should be combined into larger survey areas to generate the baseline data required to initiate interventions.