Design and conduct of a pragmatic randomized controlled trial to enhance smoking-cessation outcomes with exercise: The Fit2Quit study

Background: Most smokers want to stop smoking and many try to quit. However abstinence rates are low and most smokers do not manage to abstain for even a week. Relapse to smoking can be related to the occurrence of tobacco withdrawal symptoms (e.g., sleep disturbance, irritability, and craving) and weight gain. If regular exercise mitigates these effects it could have potential as an aid to smoking cessation. The aim of the Fit2Quit study is to determine the effects of a home and community-based exercise intervention on smoking abstinence at six months when used as an adjunct to usual care (telephone smoking-cessation counseling and nicotine replacement therapy; NRT). Methods/design: A prospective parallel two-arm randomized controlled trial. Participants (n = 1400, 700 per arm) will be randomized to a structured home and community-based exercise program plus usual care (behavioral counseling and NRT) or to usual-care alone. It is targeted that at least 25% of the sample will be of Mori ethnicity (New Zealand indigenous). Outcomes to be measured using intention-to-treat analysis include: seven-day point prevalence of smoking abstinence verified by salivary cotinine (primary outcome); 6 months continuous abstinence; body mass index (BMI); cardio-respiratory fitness; physical activity levels; and cost effectiveness. Discussion: The Fit2Quit study is an example of a large, pragmatic randomized controlled trial in a community setting. Specific components of the exercise intervention are outlined in detail. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000637246.

Antioxidant treatments for schizophrenia

Background: There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. Objectives: To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. Search methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria: We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. Data collection and analysis: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. Main results: The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. Authors' conclusions: Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.

Global cancer surgery : delivering safe, affordable, and timely cancer surgery

Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US $6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.

Does a combination of virtual reality, neuromodulation and neuroimaging provide a comprehensive platform for neurorehabilitation? - A narrative review of the literature

In the last decade, virtual reality (VR) training has been used extensively in video games and military training to provide a sense of realism and environmental interaction to its users. More recently, VR training has been explored as a possible adjunct therapy for people with motor and mental health dysfunctions. The concept underlying VR therapy as a treatment for motor and cognitive dysfunction is to improve neuroplasticity of the brain by engaging users in multisensory training. In this review, we discuss the theoretical framework underlying the use of VR as a therapeutic intervention for neurorehabilitation and provide evidence for its use in treating motor and mental disorders such as cerebral palsy, Parkinson’s disease, stroke, schizophrenia, anxiety disorders, and other related clinical areas. While this review provides some insights into the efficacy of VR in clinical rehabilitation and its complimentary use with neuroimaging (e.g., fNIRS and EEG) and neuromodulation (e.g., tDCS and rTMS), more research is needed to understand how different clinical conditions are affected by VR therapies (e.g., stimulus presentation, interactivity, control and types of VR). Future studies should consider large, longitudinal randomized controlled trials to determine the true potential of VR therapies in various clinical populations.

Clinical supervision training across contexts.

BACKGROUND: Clinicians require specific skills to teach or supervise students in the workplace; however, there are barriers to accessing faculty member development, such as time, cost and suitability. The Clinical Supervision Support Across Contexts (ClinSSAC) programme was designed to provide accessible interprofessional educator training to clinical supervisors across a wide range of clinical settings. CONTEXT: In Australia there are increasing numbers of health care students, creating pressure on existing placements. Students are now increasingly learning in community settings, where clinicians have traditionally had less access to faculty member development. INNOVATION: An interprofessional team collaborated in the development and implementation of ClinSSAC. A total of 978 clinicians participated in a face-to-face, interactive, introductory module to clinical supervision; 672 people accessed the equivalent online core module, with 23 per cent completing all activities. Additional profession-and discipline-specific modules were also developed. IMPLICATIONS: Formal project evaluation found that most participants rated the workshops as helpful or very helpful for their roles as clinical supervisors. Interdisciplinary learning from the workshops was reported to enable cross-discipline supervision. Large participant numbers and favourable ratings indicate a continuing need for basic training in education. Key factors to workshop success included expert facilitators, the interprofessional context and interactive model. The online modules were an important adjunct, and provided context-specific resources, but the low online completion rate suggests protected face-to-face time for faculty member development is still required. Programmes such as ClinSSAC have the capacity to promote interprofessional education and practice. There are barriers to accessing faculty member development, such as time, cost and suitability.

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms

BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ.

METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes.

DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine.

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

Development and evaluation of a computer-based, self-management tool for people recently diagnosed with type 2 diabetes

Aim. The purpose of this study was to develop and evaluate a computer-based, dietary, and physical activity self-management program for people recently diagnosed with type 2 diabetes. Methods. The computer-based program was developed in conjunction with the target group and evaluated in a 12-week randomised controlled trial (RCT). Participants were randomised to the intervention (computer-program) or control group (usual care). Primary outcomes were diabetes knowledge and goal setting (ADKnowl questionnaire, Diabetes Obstacles Questionnaire (DOQ)) measured at baseline and week 12. User feedback on the program was obtained via a questionnaire and focus groups. Results. Seventy participants completed the 12-week RCT (32 intervention, 38 control, mean age 59 (SD) years). After completion there was a significant between-group difference in the "knowledge and beliefs scale" of the DOQ. Two-thirds of the intervention group rated the program as either good or very good, 92% would recommend the program to others, and 96% agreed that the information within the program was clear and easy to understand. Conclusions. The computer-program resulted in a small but statistically significant improvement in diet-related knowledge and user satisfaction was high. With some further development, this computer-based educational tool may be a useful adjunct to diabetes self-management. This trial is registered with clinicaltrials.gov NCT number NCT00877851.

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

Investigating automated chemical evolution of oil-in-water droplets

One of the main unresolved questions in science is how non-living matter became alive in a process known as abiognesis, which aims to explain how from a primordial soup scenario containing simple molecules, by following a ``bottom up'' approach, complex biomolecules emerged forming the first living system, known as a protocell. A protocell is defined by the interplay of three sub-systems which are considered requirements for life: information molecules, metabolism, and compartmentalization. This thesis investigates the role of compartmentalization during the emergence of life, and how simple membrane aggregates could evolve into entities that were able to develop ``life-like'' behaviours, and in particular how such evolution could happen without the presence of information molecules. Our ultimate objective is to create an autonomous evolvable system, and in order tp do so we will try to engineer life following a ``top-down'' approach, where an initial platform capable of evolving chemistry will be constructed, but the chemistry being dependent on the robotic adjunct, and how then this platform can be de-constructed in iterative operations until it is fully disconnected from the evolvable system, the system then being inherently autonomous. The first project of this thesis describes how the initial platform was designed and built. The platform was based on the model of a standard liquid handling robot, with the main difference with respect to other similar robots being that we used a 3D-printer in order to prototype the robot and build its main equipment, like a liquid dispensing system, tool movement mechanism, and washing procedures. The robot was able to mix different components and create populations of droplets in a Petri dish filled with aqueous phase. The Petri dish was then observed by a camera, which analysed the behaviours described by the droplets and fed this information back to the robot. Using this loop, the robot was then able to implement an evolutionary algorithm, where populations of droplets were evolved towards defined life-like behaviours. The second project of this thesis aimed to remove as many mechanical parts as possible from the robot while keeping the evolvable chemistry intact. In order to do so, we encapsulated the functionalities of the previous liquid handling robot into a single monolithic 3D-printed device. This device was able to mix different components, generate populations of droplets in an aqueous phase, and was also equipped with a camera in order to analyse the experiments. Moreover, because the full fabrication process of the devices happened in a 3D-printer, we were also able to alter its experimental arena by adding different obstacles where to evolve the droplets, enabling us to study how environmental changes can shape evolution. By doing so, we were able to embody evolutionary characteristics into our device, removing constraints from the physical platform, and taking one step forward to a possible autonomous evolvable system.

Uso de dexmedetomidina como tratamiento coadyuvante de síndrome de abstinencia alcohólica: revisión sistemática

El objetivo de este estudio es establecer si la dexmedetomidina (DEX) es segura y efectiva para el manejo coadyuvante de síndrome de abstinencia a alcohol (SAA) a través de la búsqueda de evidencia científica. Metodología: se realiza una revisión sistemática de literatura publicada y no publicada desde enero de 1989 hasta febrero 2016 en PubMed, Embase, Scopus, Bireme, Cochrane library y en otras bases de datos y portales. Los criterios de inclusión fueron ensayos clínicos aleatorizados y no aleatorizados, estudios cuasi-experimentales, estudios de cohorte, y estudios de casos y controles; que incluyeron pacientes mayores de 18 años hospitalizados con diagnóstico de SAA y donde se usó DEX como terapia coadyuvante. Resultados: 7 estudios, 477 pacientes, se incluyeron en el análisis final. Se encontraron dos ensayos clínicos aleatorizados, tres estudios de casos y controles y dos estudios de cohorte retrospectivo. Solo uno de los estudios fue doble ciego y utilizó placebo como comparador. Análisis y conclusiones: en los estudios experimentales se determinan que el uso de DEX como terapia coadyuvante en el manejo de SAA tiene significancia clínica y estadística para disminuir dosis de BZD en las primeras 24 horas de tratamiento; pero no demostraron tener otros beneficios clínicos. En los estudios no aleatorizados existe consenso que relaciona el uso de DEX con menores dosis de BZD de forma temprana. Recomendaciones: no se recomienda el uso de DEX en SAA de forma rutinaria. Se recomienda usar DEX solo en casos en el que exista evidencia fallo terapéutico a BZD.

Curva de aprendizaje para ecografía cardiaca en residentes de primer y segundo año de medicina crítica de la universidad del rosario en el año 2016

La ecografía básica cardiaca (ECB) es una herramienta útil en la Unidad de Cuidados intensivos al facilitar la realización de ciertas intervenciones. No se ha definido el número de repeticiones necesarias para obtener un nivel de competencia adecuado. La evidencia encontrada indica un número mínimo de cincuenta repeticiones, para alcanzar cierto grado de habilidad.

Descripción de la prevalencia del boarding en la fundación santa fe de bogotá.

Introducción: El boarding es el fenómeno que ocurre cuando existen pacientes hospitalizados en urgencias sin una cama de hospitalización a la cual trasladarse, en la literatura mundial se ha identificado como un factor que repercute en la calidad y seguridad de la atención en urgencias. Este trabajo busca describir la prevalencia de dicho fenómeno en el servicio de urgencias de la Fundación Santa fe de Bogotá Metodología: Estudio observacional de prevalencia. Se incluyeron pacientes del mes de octubre de 2015 atendidos por especialistas en medicina de emergencias de la Fundación Santa fe de Bogotá. Se tomaron datos del turno realizado (mañana, tarde y noche), y datos del servicio de urgencias para su descripción. Resultados: La mediana de ocupación por boarding en urgencias fue del 68% con un rango intercuartil de 54-75%; en términos de tiempo en minutos, la mediana fue de 1054 minutos, con un rango intercuartil de 621-1490. Existen diferencias numéricas del tiempo en minutos de acuerdo el turno (mañana: 992,77 DE 519, tarde:1584,13 DE 1000,27 noche:1304,13 DE 2126,43). Discusión: El tiempo de boarding reportado para urgencias de la Fundación Santa fe de Bogotá es comparativamente mayor al descrito en la literatura mundial, se deben explorar en estudios analíticos posteriores los factores o variables que se asocien a la presencia de este fenómeno.