Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

Fingertip amputation injuries are common in all ages. Conservatively treated fingertips can regenerate skin and soft tissues to form a functionally and cosmetically excellent new fingertip. Little is known about this ability that, in humans, is confined to the fingertips. Even less is known about the role of the bacteria that regularly colonize these wounds without negative impact on regeneration and healing. As an alternative to surgery, self-adhesive film dressings are commonly used to establish a wet chamber around the injury. These dressings leak malodorous wound fluid eventually until the wound is dry. Having that into consideration, we have therefore developed a silicone finger cap that forms a mechanically protected, wet chamber around the injury for optimal regeneration conditions. It contains a puncturable reservoir for excess wound fluid, which can be thus routinely analyzed for diagnostic and research purposes. This study protocol explains the first randomized controlled trial (RCT) on the semiocclusive treatment of fingertip amputations in both children and adults comparing traditional film dressings with the novel silicone finger cap. Being the first RCT using 2 medical devices not yet certified for this indication, it will gather valuable information for the understanding of fingertip regeneration and the design of future definitive studies.

Introduction: Dementia is a syndrome due to disease of the brain, usually of a chronic nature, in which there is disturbance of multiple higher cortical functions including Memory, Comprehension, Thinking, Judgment, Orientation, language and communication skills and abstract thinking. It is one of the most challenging disorders both in terms of prevalence and economic burden. There are currently approximately 800,000 people with dementia in UK and national cost is 17 billion per year. It is estimated that in next thirty years, number of people with dementia will increase to 1.4 million and the national cost will be over 50 billion. The exceptional advances in modern medicine in terms of prolonging life expectancy do not necessarily improve the care delivered to people with dementia. Dementia is a progressive condition where clinical recovery is not possible despite the discovery of cognition enhancing drugs. This belief leads to low expectations that tend to erode hope and foster indignity. Advances in treatment of Alzheimer’s disease have, however, stimulated new thinking and methods of service delivery. At certain stage of their illness, if not from the very beginning, personal, and social recovery becomes more meaningful for service users than their clinical recovery. Objective: To investigate whether recovery-orientated psychiatric assessment and therapeutic intervention enhances the wellbeing of people with memory problems and their family carers. Method: This study was a preliminary randomised control study. Patients were randomly allocated to recovery focus group or treatment as usual group acting as the control. Participants in the recovery focus group received a recovery-focused pre-diagnostic wellbeing assessment and counselling, diagnostic consultation with written feedback and post-diagnostic support over a period of six months. Participants in both groups were assessed using the WHO Wellbeing Index (WHO-5) as the primary outcome measure. The Mini Mental State Examination, Cornell Scale for Depression in Dementia, EuroQol-5D and Zarit Burden Interview were used as secondary outcome measures. Written records of the narrative accounts of participants in the recovery focus group were also obtained. Results: 48 patients with early dementia were recruited and agreed to take part in the study. Out of these, 34 patients completed the study, of which 17 patients were in the recovery focus group and 17 patients were in the treatment as usual group (control).There was a significant difference between the groups in terms of greater improvement in wellbeing as rated by the WHO – 5 Wellbeing Index in the recovery focus group compared to the control group. The secondary outcome measures in the areas of cognition, quality of life and caregiver burden showed no differences between the groups. However, case histories from the recovery focus group identified the main areas of improvement in improved mood, increased social interaction, reduction in carer strain and/or burden and improved self-worth and/or confidence. Conclusions: This study shows that recovery focused care can enhance the wellbeing of people with mild to moderate dementia. The additional benefits perceived by the patients and their relatives /carers include improvement in mood symptoms, social interaction and confidence as well as reduction in carer burden and strain.

Purpose: To test whether a psycho-educational program affects mental wellbeing in persons treated for colorectal cancer and their next-of-kin. Design: A prospective, longitudinal, randomized controlled trial. Setting: Surgical clinic at a university hospital in Sweden. Sample: 105 colorectal cancer patients and 71 next-of-kin were allocated to a psycho­educational program or to standard care. Methods: Mental wellbeing was evaluated with the Mood Adjective Check List and The Hospital Anxiety and Depression Scale at baseline and at 1, 6, and 12 months. The program consisted of seven meetings, including lecture and time for reflection with other patients/next­of-kin. Main Research Variable: Overall mood, activity, calmness, pleasantness, anxiety, and depression. Findings: The psycho-educational program increased overall mood, calmness, and pleasantness among patients after one month but had no effect on activity, anxiety, or depression. The program had no effect on the overall mood, activity, calmness, pleasantness, anxiety, or depression among next-of-kin. Conclusion: The psycho-educational program had a short-term effect on overall patient mood, calmness, and pleasantness but not on next-of-kin. Implications for Nursing: A psycho-educational program including lecture and time for reflection can be used with a colorectal cancer patient population to improve some aspects of their mental wellbeing.

Purpose: Postnatal depression has significant negative outcomes for both mother and baby. Cognitive-behavioural interventions have proven promising in its treatment, but there are a number of barriers, specific to the postnatal period, which lead to low take-up of treatment. Online interventions may circumvent some of these barriers. However, evidence of long-term follow-up is sparse, in spite of the importance of knowing how such treatments work over the longer-term. Methods: Long-term follow-up of postnatal women participating in a feasibility randomised controlled trial of NetmumsHWD, an online behavioural activation treatment with telephone support. Results: Retention rates of over 70 percent were obtained. There were small but non-significant effects of treatment on depressive symptomology and behavioural activation scores at 16 months post-randomisation. Baseline depression and behavioural activation scores predicted attrition prior to the implementation of outreach strategies for data collection; these systematic differences in attrition disappeared post-implementation. Measures of treatment adherence were not related to outcome. Conclusions: Collection of long-term follow-up data from postnatal women appears feasible. The findings demonstrate the importance of outreach in maximising retention, especially in relation to the generalizability of results. Future research should consider ways to assess treatment engagement and its relationship with outcome.

The primary aim was to compare the effectiveness of smoking cessation interventions of different intensities in a clinical dental and a telephone setting in Sweden. Methods: A total of 300 smokers were randomized to High or Low Intensity Treatment (HIT or LIT) at the Public Dental Service, County Council of Västmanland. Effectiveness (abstinence rate) was measured after 1yr (paper I) and 5-8yrs (paper III). A cost-effectiveness analysis was conducted, based on intervention costs, number of abstinent participants after 1yr, and a Markov modelling of future costs and health (in QALYs) consequences (paper II). In paper IV, 586 callers to the Swedish National Tobacco Quitline (SNTQ) were randomized to high-intensity proactive or low-intensity reactive service, and effectiveness was measured after 1 yr. Effectiveness measures were self-reported point prevalence, 6-month continuous abstinence, and sustained abstinence. Results: Absolute quit rates were 7% higher with HIT than with LIT on all measures and increased by 8% from 1yr to 5-8yrs. Point prevalence was 23% vs. 16% (p=.11) after 1yr and 31% vs. 24% (p=.16) after 5-8yrs. Six-month continuous abstinence was 18% vs. 9% (p =.02) after 1yr and 26% vs.19% (p=.18) after 5-8yrs. Sustained abstinence was 12% vs. 5% (p =.03) after 5-8yrs. Nicotine dependence was a strong predictor for abstinence at 1yr and achieved abstinence at 1yr was a strong predictor for abstinence at long-term follow-up. The cost-effectiveness analysis showed that both HIT and LIT were cost-effective, and LIT was even cost-saving compared with doing nothing. HIT was more costly and more effective than LIT, and the cost of each extra QALY gained by HIT was 100,000SEK, which is considered very cost-effective in Sweden. Proactice and reactive services were equally effective at the SNTQ. Point prevalence was 27% and 6-month continuous abstinence was 21% after 1yr. Being smoke-free at baseline was the strongest predictor for abstinence at 1yr. Conclusion: Support at high as well as low intensity in a clinical dental setting in Sweden and at the SNTQ was effective in achieving smoking cessation. Both high- and low-intensity interventions were very cost-effective in a clinical dental setting.

Physical inactivity among young people is a public health concern. Markers of physical inactivity, such as low cardio-respiratory fitness (CRF) and obesity are adversely related to higher order cognitive functions, which underpin goal directed behaviour (i.e. cognitive control) and are implicated in academic achievement. Regular aerobic exercise can benefit cognitive control in children. However, it remains unknown whether daily physical activity behaviour is associated with cognitive control. Investigating this is important as targeting increments in daily moderate-to-vigorous physical activity (MVPA) may initially be a more realistic policy goal than developing aerobic exercise interventions. Nominal number of studies assessed this relationship using objective monitoring of physical activity (accelerometry), and yielded mixed results. None of the studies into objectively measured physical activity and cognitive function in young people controlled for CRF, which is posited to mediate the relationship between regular aerobic exercise and cognitive control. Likewise, other important confounders such as intelligence, have yet to be addressed in the literature. Moreover, it is unknown whether this relationship varies with age, as extant studies looked solely at younger adolescents. For example, meta-analytical findings (Fedewa & Ahn, 2011) suggest that children can benefit more cognitively from CRF and chronic aerobic exercise than adolescents as greater effect sizes have been observed for younger compared to older youngsters. Alternatively, chronic aerobic exercise may be specifically needed for cognitive benefits to emerge. However, none of the aerobic exercise interventions included objective assessments of baseline physical activity and few studies assessed the effects of chronic aerobic exercise interventions on multiple indices of cognitive control. This thesis aimed to address the limitations of previous research and to investigate: 1) the associations between objectively measured daily MVPA and cognitive control in older adolescents (study 1), and 2) in preadolescent children (study 2), while controlling for CRF, general intellectual ability and a number of important confounders (e.g. adiposity, attention-deficit hyperactivity disorder); 3) the relationship between daily MVPA and academic achievement (study 2); 4) the effects of chronic aerobic exercise intervention on cognitive control in children, while controlling for objectively measured daily MVPA and time sedentary at baseline (study 3). Methods: Study 1. A sample of 667 adolescents (Mage = 15.4, SD = .17, 55.5% girls) from the Avon Longitudinal Study of Parents and Children was included in the analyses. MVPA was measured with ActiGraph, GT1M accelerometer. CRF was assessed with sub-maximal cycle ergometer test and expressed as weight adjusted predicted physical work capacity at the heart rate of 170 beats per minute (PWC-170). Attentional control was measured with Stop Signal task. Study 2. A sample of 81 children (Mage = 8.64 years, SD = .57, 45.7 % girls) was included in the analyses. MVPA was objectively measured using the ActiGraph, wGT3X+ accelerometer. CRF was measured using a maximal graded exercise test on a treadmill. Inhibitory control was assessed with a modified Eriksen flanker task, working memory with Operation Span Task; and academic achievement with Kaufman Test of Educational Achievement. Study 3. 32 children (Mage = 8.64, SD = .58, 56.2% girls) were randomised into a physical activity intervention (FITKids2) or a waitlist control group. Changes in VO2max were measured using a maximal graded treadmill exercise test and changes in MVPA were objectively monitored for 7 days using the ActiGraph, wGT3X+ accelerometer. Behavioural measures of inhibition (reaction time, and accuracy) and working memory (accuracy) were taken using computerised laboratory tasks (modified Eriksen flanker task and Operation Span Task). Results: Study 1. MVPA was not significantly related to cognitive processing speed or variability of cognitive performance in hierarchical linear regression models. In simple regression models, CRF was negatively related to mean RT on the simple go condition (R2 = 2.6%, F(1, 308) = 8.28, p = .004). Study 2. No significant associations were noted between MVPA and either inhibition, working memory, or academic achievement. In contrast, CRF explained 4.7% of variance in accuracy interference (ΔR2 = .047, p = .045; β = -.22, t(78) = 2.03, p = .045, F(2, 78) = 4.95, p = .009). Study 3. FITKids2 physical activity intervention had a positive effect on the speed of responding during incongruent condition of flanker task (F(1, 30) = 4.69, p = .038, ηp2 = .13). A significant increase in BMI percentile was observed in the control (Z = 2.17, p = .03) but not in the intervention group (p = .53). Discussion: Study 1. Our results suggest that aerobic fitness, but not MVPA, was associated with cognitive processing speed under less cognitively demanding task conditions. The results thus indicate a potential global effect of aerobic fitness on cognitive functions in adolescents but this may differ depending on the specific task characteristics. Study 2. The results of this study suggest that CRF but not objectively measured MVPA was associated with better interference control in preadolescent children. Given the intermittent nature of children s daily MVPA, it is possible that aerobic exercise, which increases CRF is needed for cognitive benefits to emerge. Study 3. FITKids2 after-school physical activity intervention had a positive effect on children s inhibitory control, namely this cognitive function, which is closely related to academic achievement and future job and health outcomes. Thus, the results of this study convey a positive public health message, where promoting child s engagement in aerobic exercise can engender benefits to their cognitive function. Conclusions: The findings from this thesis can inform development of physical activity interventions to benefit cognitive functions in young people and contribute to the evidence base to inform future health and educational policies.

När en patient opereras i generell anestesi kan hon trots medvetslöshet uppleva smärta om hon är för ytlig i sin medvetslöshet. Kroppens fysiologiska stressrespons aktiveras, vilket visar sig genom stigande blodtryck och ökad puls. Administrering av hypnotika och analgetika eliminerar denna stress effektivt varpå risken för smärtutlösta postoperativa komplikationer minskas. Eftersom den farmakologiska behandlingen också medför en ökad risk för postoperativa biverkningar såsom illamående, kräkning och trötthet skulle det vara av värde att hitta en icke-farmakologisk behandling som har god smärtstillande effekt men saknar postoperativa biverkningar. En systematisk litteraturöversikt har visat att musik har lugnande effekt preoperativt och en annan litteraturöversikt har visat på smärthämmande effekter på vakna patienter både under och efter operation. Det saknas översikter som värderat musikens effekter på patienter under generell anestesi. Syftet med denna litteraturstudie är därför att värdera aktuella forskningsresultat gällande musikens påverkan på dessa patienter. Sökningen resulterade i sju interventionsstudier, varav fyra var randomiserade kontrollerade studier (RCT). De var jämförbara och av hög kvalitet men hade lågt deltagarantal (n=20-51 deltagare/grupp). Musiken (naturljud och instrumentella lugnande ljud) gav intraoperativa effekter såsom sänkt blodtryck och minskat behov av analgetika. Dessutom resulterade den i postoperativa effekter såsom minskad smärta och fortsatt minskat behov av analgetika, ökad tillfredställande upplevelse av anestesin och en snabbare mobilisering. Effekter som kan minska vårdlidandet för patienten. Resultatet indikerar att musik under generell anestesi har en positiv inverkan på patienter, men eftersom studierna är få till antalet och har små studiepopulationer kan inga säkra slutsatser dras om huruvida musik är en metod som skall införas i vården. / Program: Specialistsjuksköterskeutbildning med inriktning mot anestesisjukvård

The recent inclusion of complex posttraumatic stress disorder (CPTSD) within the International Classification of Diseases, eleventh edition (ICD-11) prompted scholars to re-evaluate treatment guidelines for traumatic disorders. The present study aimed to conceptualize dyadic, community, and systemic connections within the context of ICD-11 traumatic disorders and investigate unique associations between factors capturing relational quality. The current study additionally utilized a novel network modeling approach to explore the CPTSD symptom network structure using a college sample of trauma survivors. Consistent with generations of theory and research, relational quality factors associated with the disturbances in self-organization (DSO) symptom cluster, and anticipated discrimination associated with both relational disturbance and sense of threat. Affect dysregulation, re-experiencing, and relational engagement emerged as most central within the CPTSD symptom network, providing evidence towards the role of affect regulation in relational functioning, while intersectional discrimination associated with both the PTSD and DSO symptom clusters. Findings from the present study provide context to the potential application of a relational and systems focused intervention.

<p>In a Manila hospital, 204 mothers were randomized into three groups: two intervention groups receiving home-based counseling visits, one of them (n=68) by counselors trained to use a locally developed, two-tiered program of breastfeeding counseling, and the other by counselors trained in general childcare (n=67), were compared with a control group of mothers (n=69) who did not receive any counseling. All infants were scheduled for seven visits to the hospital for follow-up. During hospital visits, maternal and infant body measurements were made and an independent interviewer asked the mothers individually to recall how the infant had been fed. One study physician, blind to participant groups, was consulted at all scheduled and unscheduled infant visits.</p><p>At six months, 44% of the breastfeeding-counseled mothers, 7% of the childcare-counseled mothers and none of the mothers in the control group were exclusively breastfeeding. Twenty- four mothers breastfed exclusively during the first six months, of whom 22 received breastfeeding counseling and 2 had no breastfeeding counseling. Among 24 infants who were exclusively breastfed from birth to six months there were no episodes of diarrhea. All infants had gained in weight, length and head circumference. Mean maternal weight loss at six months was similar whether her breastfeeding was exclusive or partial.</p><p>The reasons why mothers without breastfeeding counseling introduced non-breast milk feeding before six months reflected lack of knowledge and support. Breastfeeding support during the first six months focusing on how to prevent and solve breastfeeding problems, particularly during the first two weeks, will enable mothers to choose to breastfeed exclusively up to six months. </p><p>This study has provided fundamental evidence of successful intervention by breastfeeding counseling to achieve six months of exclusive breastfeeding among term, low-birthweight infants. The locally developed training program in breastfeeding counseling, which successfully prepared volunteers to counsel mothers at home, could be incorporated into primary health care in the Philippines. Mothers who received breastfeeding counseling appreciated how this helped them to achieve their breastfeeding goals for the first six months. Improved breastfeeding practices as a result of breastfeeding counseling provided infants with protection from diarrhea and respiratory infections, contributing to their health and development.</p>