Alzheimer's disease multiple intervention trial (ADMIT): study protocol for a randomized controlled clinical trial

ABSTRACT: BACKGROUND: Given the current lack of disease-modifying therapies, it is important to explore new models of longitudinal care for older adults with dementia that focus on improving quality of life and delaying functional decline. In a previous clinical trial, we demonstrated that collaborative care for Alzheimer's disease reduces patients' neuropsychiatric symptoms as well as caregiver stress. However, these improvements in quality of life were not associated with delays in subjects' functional decline. Trial design Parallel randomized controlled clinical trial with 1:1 allocation. Participants A total of 180 community-dwelling patients aged [greater than or equal to]45 years who are diagnosed with possible or probable Alzheimer's disease; subjects must also have a caregiver willing to participate in the study and be willing to accept home visits. Subjects and their caregivers are enrolled from the primary care and geriatric medicine practices of an urban public health system serving Indianapolis, Indiana, USA. Interventions All patients receive best practices primary care including collaborative care by a dementia care manager over two years; this best practices primary care program represents the local adaptation and implementation of our prior collaborative care intervention in the urban public health system. Intervention patients also receive in-home occupational therapy delivered in twenty-four sessions over two years in addition to best practices primary care. The focus of the occupational therapy intervention is delaying functional decline and helping both subjects and caregivers adapt to functional impairments. The in-home sessions are tailored to the specific needs and goals of each patient-caregiver dyad; these needs are expected to change over the course of the study.Objective To determine whether best practices primary care plus home-based occupational therapy delays functional decline among patients with Alzheimer's disease compared to subjects treated in the control group. Outcomes The primary outcome is the Alzheimer's Disease Cooperative Studies Group Activities of Daily Living Scale; secondary outcome measures are two performance-based measures including the Short Physical Performance Battery and Short Portable Sarcopenia Measure. Outcome assessments for both the caregiver-reported scale and subjects' physical performance scales are completed in the subject's home. Randomization Eligible patient-care giver dyads will be stratified by clinic type and block randomized with a computer developed randomization scheme using a 1:1 allocation ratio. Blinding Single blinded. Research assistants completing the outcome assessments were blinded to the subjects' treatment group. Trial status Ongoing ClinicalTrial.Gov identifier NCT01314950; date of completed registration 10 March 2011; date first patient randomized 9 March 2011.     

A diversity of beta diversities: straightening up a concept gone awry. Part 2. Quantifying beta diversity and related phenomena

The present two-part review aims to put the different phenomena that have been called beta diversity over the years into a common conceptual framework and to explain what each of them measures. The first part (Tuomisto 2010) discussed basic definitions of beta diversity. Each arises from a different way of combining a definition of diversity with a definition of its alpha component and with a mathematical relationship between the alpha and gamma components. This second part assumes that an appropriate basic definition of a beta component (which may or may not be true beta diversity) has been chosen, and the focus here will be on how to quantify it for a given dataset. About twenty different approaches have been used for this purpose. It turns out that only two of these approaches accurately quantify the selected beta component: one does so for the entire dataset, and the other for two sampling units at a time. The other approaches actually quantify other phenomena, such as mean species turnover between sampling units, compositional gradient length (with or without reference to an external gradient), distinctness of a focal sampling unit, rate of species accumulation with increasing sampling effort, rate of compositional turnover along an external gradient, or the rate of decay in compositional similarity with increasing geographical distance. Although most of these phenomena can be expressed as a function of a beta component of diversity, they do not equal a beta component of diversity. Many of these derived variables are not even numerically correlated with the beta component on which they are based, which needs to be taken into account when interpreting the results. The effects of sampling decisions when results are extrapolated beyond the available data will also be discussed.     

Research of the Holiday kind: Tabulating Ingestion of Mocha Solution (TIMS): a longitudinal prospective cohort study

The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption.     

The experiences of pregnant women in an interventional clinical trial: Research In Pregnancy Ethics (RIPE) study

There is increasing global pressure to ensure that pregnant women are responsibly and safely included in clinical research in order to improve the evidence base that underpins healthcare delivery during pregnancy. One supposed barrier to inclusion is the assumption that pregnant women will be reluctant to participate in research. There is however very little empirical research investigating the views of pregnant women. Their perspective on the benefits, burdens and risks of research is a crucial component to ensuring effective recruitment. The Research In Pregnancy Ethics (RIPE) study set out to ascertain the views of pregnant women about research participation using an inductive thematic analysis. We conducted semi‐structured interviews with 20 women who had participated in a double‐blind randomised placebo controlled trial in Wellington (New Zealand) while pregnant. Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes. Key motivations for participating were altruism, playing a valuable civic role and the importance of research. The main perceived burdens related to inconvenience and time commitment. For some women, possible randomization to the placebo arm was regarded as a burden or disadvantage.     

A diversity of beta diversities: straightening up a concept gone awry. Part 1. Defining beta diversity as a function of alpha and gamma diversity

The term beta diversity has been used to refer to a wide variety of phenomena. Although all of these encompass some kind of compositional heterogeneity between places, many are not related to each other in any predictable way. The present two‐part review aims to put the different phenomena that have been called a beta component of diversity into a common conceptual framework, and to explain what each of them measures. In this first part, the focus is on defining beta diversity. This involves deciding what diversity is and how the observed total or gamma diversity (γ) is partitioned into alpha (α) and beta (β) components. Several different definitions of “beta diversity” that result from these decisions have been used in the ecological literature. True beta diversity is obtained when the total effective number of species in a dataset (true gamma diversityγ) is multiplicatively partitioned into the effective number of species per compositionally distinct virtual sampling unit (true alpha diversityα_d) and the effective number of such compositional units (β_Md=γ/α_d). All true diversities quantify the effective number of types of entities. Because the other variants of “beta diversity” that have been used by ecologists quantify other phenomena, an alternative nomenclature is proposed here for the seven most popular beta components: regional‐to‐local diversity ratio, two‐way diversity ratio, absolute effective species turnover (=regional diversity excess), Whittaker's effective species turnover, proportional effective species turnover, regional entropy excess and regional variance excess. In the second part of the review, the focus will be on how to quantify these phenomena in practice. This involves deciding how the sampling units that contribute to total diversity are selected, and whether the entity that is quantified is all of “beta diversity”, a specific part of “beta diversity”, the rate of change in “beta diversity” in relation to a given external factor, or something else.     

A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial.

OBJECTIVE: To compare aspirin with anticoagulation with regard to risk of cardiac death and reinfarction in patients who received anistreplase thrombolysis for myocardial infarction. DESIGN: A multicentre unblinded randomised clinical trial. SETTING: 38 hospitals in six countries. SUBJECTS: 1036 patients who had been treated with anistreplase for myocardial infarction were randomly assigned to either aspirin (150 mg daily) or anticoagulation (intravenous heparin followed by warfarin or other oral anticoagulant). The trial was stopped earlier than originally intended because of the slowing rate of recruitment. MAIN OUTCOME MEASURE: Cardiac death or recurrent myocardial infarction at 30 days. RESULTS: After 30 days cardiac death or reinfarction, occurred in 11.0% (57/517) of the patients treated with anticoagulation and 11.2% (58/519) of the patients treated with aspirin (odds ratio 1.02, 95% confidence interval 0.69 to 1.50, P = 0.92). Corresponding findings at three months were 13.2% (68/517) and 12.1% (63/519) (0.91, 0.63 to 1.32, P = 0.67). Patients receiving anticoagulation were more likely than patients receiving aspirin to have had severe bleeding or a stroke by three months (3.9% v 1.7% (0.44, 0.20 to 0.97, P = 0.04)). CONCLUSION: No evidence of a difference in the incidence of cardiac events was found between the two treatment groups, though the trial is too small to claim treatment equivalence confidently. A higher incidence of severe bleeding events and strokes was detected in the group receiving anticoagulation, suggesting that aspirin may be the drug of choice for most patients in this context.     

A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials

Background

There is a large treatment gap with few community services for people with schizophrenia in low income countries largely due to the shortage of specialist mental healthcare human resources. Community based rehabilitation (CBR), involving lay health workers, has been shown to be feasible, acceptable and more effective than routine care for people with schizophrenia in observational studies. The aim of this study is to evaluate whether a lay health worker led, Collaborative Community Based Care (CCBC) intervention, combined with usual Facility Based Care (FBC), is superior to FBC alone in improving outcomes for people with schizophrenia and their caregivers in India.

Methods/Design

This trial is a multi-site, parallel group randomised controlled trial design in India. The trial will be conducted concurrently at three sites in India where persons with schizophrenia will be screened for eligibility and recruited after providing informed consent. Trial participants will be randomly allocated in a 2:1 ratio to the CCBC+FBC and FBC arms respectively using an allocation sequence pre-prepared through the use of permuted blocks, stratified within site. The structured CCBC intervention will be delivered by trained lay community health workers (CHWs) working together with the treating Psychiatrist. We aim to recruit 282 persons with schizophrenia. The primary outcomes are reduction in severity of symptoms of schizophrenia and disability at 12 months. The study will be conducted according to good ethical practice, data analysis and reporting guidelines.

Discussion

If the additional CCBC intervention delivered by front line CHWs is demonstrated to be effective and cost-effective in comparison to usually available care, this intervention can be scaled up to expand coverage and improve outcomes for persons with schizophrenia and their caregivers in low income countries.

Trial registration

The trial is registered with the International Society for the Registration of Clinical Trials and the allocated unique ID number is ISRCTN 56877013.     

Transfer of manualized CBT for social phobia into clinical practice (SOPHO-PRAX): a study protocol for a cluster-randomized controlled trial

ABSTRACT: BACKGROUND: Cognitive-behavioral therapy (CBT) is generally known to be efficacious in the treatment of social phobia when applied in RCT's, namely when the treatment manual is based on the Clark-Wells approach. However, little is known about the efficacy of manualized treatments in routine clinical practice (Phase IV of psychotherapy research). The present study (SOPHO-PRAX) is a continuation of a large multi-centre randomized clinical trial (SOPHO-NET) and analyses the extent to which additional training practitioners in manualized procedures enhances treatment effect. METHODS: N = 36 private practitioners will be included in three treatment centres and randomly designated to either training in manualized CBT or no specific training. The treatment effects of the therapies conducted by both groups of therapists will be compared. A total of 162 patients (N = 116 completers; N = 58 per condition) will be enrolled. Liebowitz Social Anxiety Scale (LSAS) will serve as primary outcome measure. Remission from social phobia is defined as LSAS total [less than or equal to] 30 points. Data will be collected at treatment begin, after 8, 15, and 25 sessions (50 mins. each), at treatment completion, as well at 6 and 12 months post-treatment. DISCUSSION: The present CBT trial combines elements of randomized-controlled trials and naturalistic studies in an innovative way. It will directly inform about the incremental effects of procedures established in a controlled trial into clinical practice. Study results are relevant to health care decisions and policy. They may serve to improve quality of treatment, and shorten the timeframe between the development and widespread dissemination of effective methods, thereby reducing health cost expenditures. The results of this study will not only inform about the degree to which the new methods lead to an improvement of treatment course and outcome, but also about whether the effects of routine psychotherapeutic treatment are comparable to those of the controlled, strictly manualized treatments of the SOPHO-NET study. Trial Registration: ClinicalTrials.gov identifier: NCT01388231. This study was funded by the German Federal Ministry of Education and Research (SOPHO-NET: BMBF 01GV0607; SOPHO-PRAX: BMBF 01GV1001).     

A contribution to the study of acute schistosomiasis (an experimental trial)

In an attempt to establish an experimental model of acute schistosomiasis, sequential histological changes were investigated in the skin, lung, liver and spleen of mice infected with 30 or 100 cercariae of Schistosoma mansoni according to four sets of experiments: single infection, repeated infections, unisexual infection and infection in mice born from infected mothers. Animals were killed every other day from exposure up to 50 days after infection. Only mild, isolated, focal inflammatory changes were found before the appearance of mature eggs in the liver, even when repeated infections were made. Severe changes of reactive hepatitis and splenitis appeared suddenly when the first mature eggs were deposited, around the 37th to 42nd day after infection. The mature eggs induced lytic and coagulative necrosis of hepatocytes around them which was soon followed by dense infiltration of eosinophils. So, mature egg-induced lesions appeared as the major factors in the pathogenesis of acute schistosomiasis in mice. Mice born from infected mothers were apparently able to rapidly modulate the egg-lesions, forming early fibrotic granulomas. The murine model of acute schistosomiasis appeared adequate for the study of pathology and pathogenesis of acute schistosomiasis.     

(Cost)-effectiveness of a multi-component intervention for adults with epilepsy: study protocol of a Dutch randomized controlled trial (ZMILE study)

Background

In patients with epilepsy, poor adherence to anti-epileptic drugs has been shown to be the most important cause of poorly controlled epilepsy. Furthermore, it has been noted that the quality of life among patients with epilepsy can be improved by counseling and treatments aimed at increasing their self-efficacy and concordance, thus stimulating self-management skills. However, there is a need for evidence on the effectiveness of such programs, especially within epilepsy care. Therefore, we have developed a multi-component intervention (MCI) which combines a self-management/education program with e-Health interventions. Accordingly, the overall objective of this study is to assess the (cost)-effectiveness and feasibility of the MCI, aiming to improve self-efficacy and concordance in patients with epilepsy.

Methods

A RCT in two parallel groups will be conducted to compare the MCI with a control condition in epilepsy patients. One hundred eligible epilepsy patients will be recruited and allocated to either the intervention or control group. The intervention group will receive the MCI consisting of a self-management/education program of six meetings, including e-Health interventions, and will be followed for 12 months. The control group will receive care as usual and will be followed for 6 months, after which patients will be offered the possibility of participating in the MCI. The study will consist of three parts: 1) a clinical effectiveness study, 2) a cost-effectiveness study, and 3) process evaluation. The primary outcome will be self-efficacy. Secondary outcomes include adherence, side effects, change in seizure severity & frequency, improved quality of life, proactive coping, and societal costs. Outcome assessments will be done using questionnaires at baseline and after 3, 6, 9, and 12 months (last two applicable only for intervention group).

Discussion

In times of budget constraints, MCI could be a valuable addition to the current healthcare provision for epilepsy, as it is expected that higher concordance and self-efficacy will result in reduced use of healthcare resources and an increased QOL. Accordingly, this study is aimed helping patients to be their own provider of health care, shifting epilepsy management from professionals to self-care by patients equipped with appropriate skills and tools.

Trial registration number

NTR4484.

     

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. METHODS: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.orControl group: Standard GP care, with referral to secondary care as required, but no access to ICCD.Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.Trial registration[ClinicalTrials.gov: Identifier NCT00945204].     

Going going gone: the loss of a reef building gastropod (Mollusca: Caenogastropoda: Vermetidae) in the southeast Mediterranean Sea

A new harvestman species, Rilaena artvinensis sp. n. (Opiliones: Phalangiidae), is described and illustrated based on males collected in north-eastern Anatolia, Turkey. The new species is similar to R. buresi (?ilhavý, 1965 ?ilhavý, V. (1965): Die Weberknechte der Unterordnung Eupnoi aus Bulgarien; zugleich eine Revision europäischer Gattungen der Unterfamilien Oligolophinae und Phalangiinae (Arachnoidea, Opilionidea). Acta Entomologica Bohemoslovaca, 62, 369–406. [Google Scholar]) and R. lenkoranica Snegovaya, 2007 Snegovaya, N. Y. (2007): Two new harvestman species from Lenkoran, Azerbaijan (Arachnida: Opiliones: Phalangiidae). Bulletin of the British Arachnological Society, 14, 88–92. [Google Scholar]. The differences between these species are elaborated.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:A53452BB-A85D-4BE8-8A6B-D0FC3421AFE3     

The Chronic CARe for diAbeTes study (CARAT): a cluster randomized controlled trial

Background

Diabetes is a major challenge for the health care system and especially for the primary care provider. The Chronic Care Model represents an evidence-based framework for the care for chronically ill. An increasing number of studies showed that implementing elements of the Chronic Care Model improves patient relevant outcomes and process parameters. However, most of these findings have been performed in settings different from the Swiss health care system which is dominated by single handed practices.

Methods/Design

CARAT is a cluster randomized controlled trial with general practitioners as the unit of randomization (trial registration: ISRCTN05947538). The study challenges the hypothesis that implementing several elements of the Chronic Care Model via a specially trained practice nurse improves the HbA1c level of diabetes type II patients significantly after one year (primary outcome). Furthermore, we assume that the intervention increases the proportion of patients who achieve the recommended targets regarding blood pressure (<130/80), HbA1c (=<6.5%) and low-density lipoprotein-cholesterol (<2.6 mmol/l), increases patients' quality of life (SF-36) and several evidence-based quality indicators for diabetes care. These improvements in care will be experienced by the patients (PACIC-5A) as well as by the practice team (ACIC). According to the power calculation, 28 general practitioners will be randomized either to the intervention group or to the control group. Each general practitioner will include 12 patients suffering from diabetes type II. In the intervention group the general practitioner as well as the practice nurse will be trained to perform care for diabetes patients according to the Chronic Care Model in teamwork. In the control group no intervention will be applied at all and patients will be treated as usual. Measurements (pre-data-collection) will take place in months II-IV, starting in February 2010. Follow-up data will be collected after 1 year.

Discussion

This study challenges the hypothesis that the Chronic Care Model can be easily implemented by a practice nurse focused approach. If our results will confirm this hypothesis the suggestion arises whether this approach should be implemented in other chronic diseases and multimorbid patients and how to redesign care in Switzerland.

     

Use of enrofloxacin in the treatment of canine brucellosis in a dog kennel (clinical trial)

To date, no totally effective antibiotic for the eradication of canine brucellosis has been found. The purpose of this study was to evaluate the efficacy of enrofloxacin in a kennel infected with Brucella canis. Twelve dogs, 2 males and 10 females (including 1 in estrus, 3 pregnant, and 6 in anestrus) infected with B. canis were given 5 mg/kg of enrofloxacin orally every 12 h for 30 days. Females received additional courses of enrofloxacin during the estral and luteal phases of the subsequent cycles (0-2 cycles). They were repeatedly mated by infected males. A serological follow-up was carried out for 38 months. The clinical, serological and bacteriological findings were recorded. In a trial carried out 14 months after the beginning of this study, all dogs were negative on the Rapid Slide Agglutination Test (RSAT). No abortions were observed. All mated female dogs conceived and gave birth to healthy puppies. Cultures of postpartum vaginal discharges (lochia) were negative for B. canis. Similar to other treatments, although enrofloxacin was not completely efficacious in treating canine brucellosis, it maintained fertility and avoided the recurrence of abortions, transmission of the disease to the puppies and dissemination of microorganisms during parturition. We inferred that enrofloxacin could be used as an alternative drug for the treatment of canine brucellosis.     

More Active Mums in Stirling (MAMMiS): a physical activity intervention for postnatal women. Study protocol for a randomised controlled trial

ABSTRACT: BACKGROUND: Many postnatal women are insufficiently physically active in the year after childbirth and could benefit from interventions to increase activity levels. However, there is limited information about the efficacy, feasibility and acceptability of motivational and behavioural interventions to promoting postnatal physical activity in the UK. METHODS: The MAMMiS study is a randomised controlled trial, conducted within a large National Health Service (NHS) region in Scotland. 76 postnatal women will be recruited to test the impact of two physical activity consultations and a 10-week group pram-walking programme on physical activity behaviour change. The intervention uses evidence-based motivational and behavioural techniques and will be systematically evaluated using objective measures (accelerometers) at 3-months, with a maintenance measure taken at 6-months follow-up. Secondary health and well-being measures and psychological mediators of physical activity change are included. DISCUSSION: The MAMMiS study will provide a test of a theoretical and evidence-based physical activity behaviour change intervention for postnatal women and provide information to inform future intervention development and testing within this population.     

More characters or more taxa for a robust phylogeny--case study from the coffee family (Rubiaceae)

Using different data sets mainly from the plant family Rubiaceae, but in parts also from the Apocynaceae, Asteraceae, Lardizabalaceae, Saxifragaceae, and Solanaceae, we have investigated the effect of number of characters, number of taxa, and kind of data on bootstrap values within phylogenetic trees. The percentage of supported nodes within a tree is positively correlated with the number of characters, and negatively correlated with the number of taxa. The morphological analyses are based on few characters and weakly supported trees are expected. The percentage of supported nodes is also dependent on the kind of data analyzed. In analyses of Rubiaceae based on the same number of characters, RFLP data give trees with higher percentage of supported nodes than rbcL and morphological data. We also discuss the support values for particular nodes at the familial and subfamilial levels. Two new data sets of ndhF and rbcL sequences of Rubiaceae are analyzed and together with earlier studies of the family we can conclude that the monophyly of the Rubiaceae is supported and within the family there are three well supported, but not easily characterized, large subfamilies, Rubioideae, Cinchonoideae s.s. and Ixoroideae s.l. There are also a few genera (Luculia and Coptosapelta) unclassified to subfamily.     

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

Background  

Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention.