Search

Background and aims: Offering financial incentives is effective for smoking cessation during pregnancy. We tested the effectiveness of financial incentives for maintaining postpartum cessation, comparing 12-month and 3-month incentives with each other and with usual care (UC). Design, setting and participants: This study was a pragmatic, multi-centre, three-arm randomized controlled trial involving four English, National Health Service, stop smoking services. A total of 462 postpartum women (aged ≥ 16 years) took part, who stopped smoking during pregnancy with financial incentives, validated as abstinent from smoking at end of pregnancy or early postpartum. Interventions: Interventions comprised (i) UC; (ii) UC plus up to £60 of financial voucher incentives offered to participants and £60 offered to an optional significant-other supporter, over 3 months postpartum, contingent upon validated abstinence ('3-month incentives'); or (iii) UC plus '3-month incentives' plus £180 of vouchers offered to participants over 9 months postpartum, contingent upon abstinence ('12-month incentives'). Measurements: Primary outcome: biochemically validated abstinence at 1 year postpartum. To adjust for testing all comparisons between groups with equal precision, P < 0.017 was necessary for significance. Secondary outcomes: self-reported and validated abstinence at 3 months postpartum; self-reported abstinence at 1 year postpartum. Findings: Primary outcome ascertainment: abstinence was 39.6% (63/159) 12 months incentives, 21.4% (33/154) 3 months incentives and 28.2% (42/149) UC. Adjusted odds ratios [95% confidence interval (CI)] = 12-month versus 3-month incentives OR = 2.41 (95% CI = 1.46-3.96), P = 0.001; 12 months versus UC 1.67 (1.04-2.70), P = 0.035; 3 months versus UC 0.69 (0.41-1.17), P = 0.174. Bayes factors indicated that for 12- month versus 3-month incentives and 12 months versus UC there was good evidence for the alternative hypothesis, and for 3 months versus UC there was good evidence for the null hypothesis. Conclusions: This randomized controlled trial provides weak evidence that up to £300 of voucher incentives over 12 months is effective for maintaining smoking abstinence postpartum compared with usual care. There was good evidence that 12-month incentives are superior to those over only 3 months, for which there was no evidence of effectiveness relative to usual care. [ABSTRACT FROM AUTHOR]

Background: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. Methods: A cross‐sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case–control study was then conducted to determine the biomarker for pruritus. Arsenite‐treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double‐blind, placebo‐controlled trial was conducted to test the efficacy of naloxone in arsenic‐exposed patients with pruritus in Shimen. Results: Hair arsenic (μg/g) showed a dose–response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate‐to‐severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum β‐endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of β‐endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic‐exposed participants in 2 weeks (β = −0.98, p = 0.04). Conclusion: Arsenic exposure is associated with pruritus, and β‐endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis. [ABSTRACT FROM AUTHOR]

Background and aims: The majority of smokers accessing the current best treatments continue to smoke. We aimed to test if e‐cigarettes (EC) compared with nicotine replacement treatment (NRT) can help such smokers to reduce smoking. Design Randomized controlled trial of EC (n = 68) versus NRT (n = 67) with 6‐month follow‐up. Setting: Stop smoking service in London, UK. Participants: A total of 135 smokers (median age = 40 years, 51% male) previously unable to stop smoking with conventional treatments. Interventions: Participants received either NRT of their choice (8‐week supply) or an EC starter pack and instructions to purchase further e‐liquids of strength and flavours of their choice themselves. Products were accompanied by minimal behavioural support. Measurements Participants who reported that they stopped smoking or reduced their daily cigarette consumption by at least 50% at 6‐month follow‐up were invited to provide a carbon monoxide (CO) reading. The primary outcome was biochemically validated reduction in smoke intake of at least 50% at 6 months and the main secondary outcome was sustained validated abstinence at 6 months. Drop‐outs were included as 'non‐reducers'. Findings Validated smoking reduction (including cessation) was achieved by 26.5 versus 6.0% of participants in the EC and NRT study arms, respectively [relative risk (RR) = 4.4, P = 0.005, 95% confidence interval (CI) = 1.6–12.4]. Sustained validated abstinence rates at 6 months were 19.1 versus 3.0% (RR = 6.4, P = 0.01, 95% CI = 1.5–27.3). Product use was high and equal in both study arms initially, but at 6 months allocated product use was 47% in the EC arm versus 10% in the NRT arm (χ2(1) = 22.0, P < 0.001), respectively. Adverse events were minor and infrequent. Conclusions: In smokers unable to quit using conventional methods, e‐cigarettes were more effective than nicotine replacement therapy in facilitating validated long‐term smoking reduction and smoking cessation when limited other support was provided. [ABSTRACT FROM AUTHOR]

Aim: Surgical site infection (SSI) is a common complication following emergency laparotomy, occurring in around 25% of patients in UK practice. The adoption of single‐use negative‐pressure dressings (SUNPDs) has been proposed as a prophylactic method of reducing the rate of SSI. The primary aim of the randomized controlled trial (RCT) described herein is to determine if a SUNPD reduces SSI at 30 days after an emergency laparotomy. Method: The Single Use Negative pRessure dressing for Reduction In Surgical site infection following Emergency laparotomy (SUNRRISE) study is an international, multicentre, pragmatic, phase III RCT with internal feasibility phase. As stated, the primary aim is to determine if a SUNPD reduces SSI at 30 days postoperatively. Patients will be randomized in a 1:1 ratio to receive either a SUNPD or a dressing of the surgeon's preference. Outcome assessors will be blinded to treatment allocation. The primary outcome measure is SSI within 30 days of surgery as defined by the US Centers for Disease Control criteria. A total of 840 patients will be required to detect a relative reduction of 40% in SSI rates (from 25% to 15%) with 90% power accounting for a 20% attrition rate. Discussion: SUNRRISE is an international, multicentre RCT evaluating the prophylactic use of SUNPD in primary closed emergency laparotomy wounds for the reduction of SSI. Our hypothesis is that a SUNPD is superior to the surgeon's preference of dressing in reducing SSIs at 30 days. The findings may influence dressing choice following emergency abdominal surgery in the future. [ABSTRACT FROM AUTHOR]

Background and aim: Reducing alcohol misuse by male prisoners is an important global issue. Control of drinking behaviour could be a useful target for intervention in this population, and locus of control could be a causal factor in this. We aimed to assess the effect of a clinical psychologist‐facilitated group intervention on male prisoners' locus of control of drinking behaviour. Design A two‐arm, single‐site, open, randomized controlled trial. Setting: A category B local training prison in South Wales, housing about 770 mainly sentenced men. Participants: Prisoners serving less than 2 years who met inclusion criteria for pre‐imprisonment alcohol misuse, alone or with drug misuse. A total of 119 were allocated to the intervention arm and 119 to the control arm; 104 and 87, respectively, completed the post‐randomization baseline interview and 68 and 60 completed a second interview approximately 4 weeks later, respectively, after intervention or treatment as usual (TAU) alone. Intervention: Nine clinical psychologist‐facilitated groups in the prison over 3 weeks. Range of participants per session was one to seven, with three to five most usual. Measures: The primary outcome was locus of control of behaviour (LCB); secondary outcomes included mental state generally (comprehensive psychiatric rating scale/CPRS) and specifically (Beck Depression Inventory/BDI). An integral process evaluation was conducted. Findings LCB scores decreased during the study, but without significant intervention effect [−1.7, 95% confidence interval (CI) = –5.1 to 1.6, P = 0.329]. Change among completers in the control group was from a mean score of 37.4 [standard deviation (SD) = 10.0] to 33.7[SD = 11.7] and in the intervention group from 37.4 (SD = 11.6) to 31.9 (SD = 11.8). Secondary outcomes, including change in mental state, did not differ between arms, but 686 (64%) sessions were lost, most because of 'prison issues'. Conclusions: A clinical psychologist‐facilitated group intervention did not have a statistically significant effect on sense of control of drinking behaviour among men with pre‐imprisonment alcohol misuse serving less than 2 years in a South Wales prison. The study proved coterminous, however, with 40% prison staff cuts which seem likely to have contributed to the high loss of group sessions and possibly overwhelmed any treatment effect. Intervention completion failures, previously cited as harmful, had no effect here, so the trial should be repeated when the prison climate improves. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To assess the cost‐effectiveness of a two‐component intervention designed to increase attendance at the NHS Stop Smoking Services (SSSs) in England. Design: Cost‐effectiveness analysis alongside a randomized controlled trial (Start2quit). Setting: NHS SSS and general practices in England. Participants: The study comprised 4384 smokers aged 16 years or more identified from medical records in 99 participating practices, who were motivated to quit and had not attended the SSS in the previous 12 months. Intervention and comparator: Intervention was a personalized and tailored letter sent from the general practitioner (GP) and a personal invitation and appointment to attend a taster session providing information about SSS. Control was a standard generic letter from the GP advertising SSS and asking smokers to contact the service to make an appointment. Measurements: Costs measured from an NHS/personal social services perspective, estimated health gains in quality‐adjusted life‐years (QALYs) measured with EQ‐5D and incremental cost per QALY gained during both 6 months and a life‐time horizon. Findings: During the trial period, the adjusted mean difference in costs was £92 [95% confidence interval (CI) = –£32 to –£216) and the adjusted mean difference in QALY gains was 0.002 (95% CI = –0.001 to 0.004). This generates an incremental cost per QALY gained of £59 401. The probability that the tailored letter and taster session is more cost‐effective than the generic letter at 6 months is never above 50%. In contrast, the discounted life‐time health‐care cost was lower in the intervention group, while the life‐time QALY gains were significantly higher. The probability that the intervention is more cost‐effective is more than 83% using a £20 000–30 000 per QALY‐gained decision‐making threshold. Conclusions: An intervention designed to increase attendance at the NHS Stop Smoking Services (tailored letter and taster session in the services) appears less likely to be cost‐effective than a generic letter in the short term, but is likely to become more cost‐effective than the generic letter during the long term. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post‐stroke pneumonia, which causes 30% of stroke‐related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post‐stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted posture, rather than direct physical rehabilitation of the swallowing function. Transcutaneous neuromuscular electrical stimulation (NMES) is a promising rehabilitation technology that can be used to stimulate swallowing; however, findings regarding efficacy have been conflicting. Aims: This pilot randomized controlled study involving three UK sites compared the efficacy of the Ampcare Effective Swallowing Protocol (ESP), combining NMES with swallow‐strengthening exercises, with usual care in order to clarify evidence on NMES in the treatment of dysphagia post‐stroke. A further objective was to pilot recruitment procedures and outcome measures in order to inform the design of a full‐scale trial. Methods & Procedures: Thirty patients were recruited and randomized into either (1) usual speech and language therapy dysphagia care; or (2) Ampcare ESP, receiving treatment 5 days/week for 4 weeks. Outcome measures included: the Functional Oral Intake Scale (FOIS), the Rosenbek Penetration‐Aspiration Scale (PAS) and patient‐reported outcomes (Swallow Related Quality of Life—SWAL‐QOL). Outcomes & Results: Thirty patients were recruited; 15 were randomized to the Ampcare ESP intervention arm and 15 to usual care. A greater proportion (75%, or 9/12) of patients receiving Ampcare ESP improved compared with 57% (or 8/14) of the usual‐care group. Patients receiving Ampcare ESP also made clinically meaningful change (a comparative benefit of 1.5 on the FOIS, and on the PAS: 1.35 for diet and 0.3 for fluids) compared with usual care. The intervention group also reported much better outcome satisfaction. Conclusions & Implications: The pilot demonstrated successful recruitment, treatment safety and tolerability and clinically meaningful outcome improvements, justifying progression to a fully powered study. It also showed clinically meaningful treatment trends for the Ampcare ESP intervention. [ABSTRACT FROM AUTHOR]

Background and Aims Premises licensed for the sale and consumption of alcohol can contribute to levels of assault-related injury through poor operational practices that, if addressed, could reduce violence. We tested the real-world effectiveness of an intervention designed to change premises operation, whether any intervention effect changed over time, and the effect of intervention dose. Design A parallel randomized controlled trial with the unit of allocation and outcomes measured at the level of individual premises. Setting All premises (public houses, nightclubs or hotels with a public bar) in Wales, UK. Participants A randomly selected subsample ( n = 600) of eligible premises (that had one or more violent incidents recorded in police-recorded crime data; n = 837) were randomized into control and intervention groups. Intervention and comparator Intervention premises were audited by Environmental Health Practitioners who identified risks for violence and provided feedback by varying dose (informal, through written advice, follow-up visits) on how risks could be addressed. Control premises received usual practice. Measurements Police data were used to derive a binary variable describing whether, on each day premises were open, one or more violent incidents were evident over a 455-day period following randomization. Findings Due to premises being unavailable at the time of intervention delivery 208 received the intervention and 245 were subject to usual practice in an intention-to-treat analysis. The intervention was associated with an increase in police recorded violence compared to normal practice (hazard ratio = 1.34, 95% confidence interval = 1.20-1.51). Exploratory analyses suggested that reduced violence was associated with greater intervention dose (follow-up visits). Conclusion An Environmental Health Practitioner-led intervention in premises licensed for the sale and on-site consumption of alcohol resulted in an increase in police recorded violence. [ABSTRACT FROM AUTHOR]

Objectives To design and evaluate the effectiveness of a pre-notification leaflet about research to increase recruitment to a randomized controlled trial (RCT). Methods A methodological, two-arm, RCT was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomized for the embedded trial, using a 1:2 ratio (intervention : control) before being randomized for REFORM. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2-3 weeks before the recruitment pack. Primary and secondary analyses were conducted using relative risk, the Cox proportional hazards model and incremental cost-effectiveness ratios. Results Of the 1436 intervention group participants, 73 (5.1%) were randomized into the REFORM trial compared with 126 (4.4%) of the 2878 control group participants. The associated relative risk (1.16) was not statistically significant [95% confidence interval (CI) 0.88-1.56]. Return rate was not significantly increased (relative risk 1.10, 95% CI 0.92-1.28) nor time to return decreased (hazard ratio: 1.11, 95% CI 0.93-1.33). Incremental cost-effectiveness ratios indicated the intervention may be cost-effective if the true estimate of effect was close to the upper bound of the associated 95% CI. Conclusion Pre-notification for potential trial participants demonstrated a small difference to randomization (0.7% difference) and return rates (1.1% difference) in favour of the intervention. Results should however be interpreted with caution as CIs for these estimates cross the point of no effect. Nevertheless, this research enhances existing evidence for pre-notification to increase recruitment rates, with further development and assessment of this potentially cost-effective intervention being recommended. [ABSTRACT FROM AUTHOR]

Objective Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug ( NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly. Methods We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin ( HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous ( SC), in addition to intramuscular ( IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD ( n = 77), 50 mg diclofenac HPβCD ( n = 76), 75 mg diclofenac HPβCD ( n = 78), or placebo ( n = 75). Results Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo ( P < 0.001 in both comparisons). Conclusion Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. Method: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. Trial registration: ISRCTN 68384912. Results: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. Conclusions: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group. [ABSTRACT FROM AUTHOR]

Background: Children who show disproportionate difficulty with the pragmatic as compared with the structural aspects of language are described as having pragmatic language impairment (PLI) or social communication disorder (SCD). Some children who have PLI also show mild social impairments associated with high-functioning autism or autism spectrum disorder (ASD). There is little robust evidence of effectiveness of speech-language interventions which target the language, pragmatic or social communication needs of these children. Aims: To evaluate the effectiveness of an intensive manualized social communication intervention (SCIP) for children who have PLI with or without features of ASD. Methods & Procedures: In a single-blind RCT design, 88 children with pragmatic and social communication needs aged 5;11-10;8, recruited from UK speech and language therapy services, were randomly assigned in a 2:1 ratio to SCIP or to treatment-as-usual. Children in the SCIP condition received up to 20 sessions of direct intervention from a specialist research speech and language therapist working with supervised assistants. All therapy content and methodology was derived from an intervention manual. A primary outcome measure of structural language and secondary outcome measures of narrative, parent-reported pragmatic functioning and social communication, blind-rated perceptions of conversational competence and teacher-reported ratings of classroom learning skills were taken pre-intervention, immediately post-intervention and at 6-month follow-up. Analysis was by intention to treat. Outcomes & Results: No significant treatment effect was found for the primary outcome measure of structural language ability or for a measure of narrative ability. Significant treatment effects were found for blind-rated perceptions of conversational competence, for parent-reported measures of pragmatic functioning and social communication, and for teacher-reported ratings of classroom learning skills. Conclusions & Implications: There is some evidence of an intervention effect on blind and parent/teacher-reported communication outcomes, but not standardized language assessment outcomes, for 6-11-year-old children who have pragmatic and social communication needs. These findings are discussed in the context of the increasingly central role of service user outcomes in providing evidence for an intervention. The substantial overlap between the presence of PLI and ASD (75%) across the whole cohort suggests that the intervention may also be applicable to some verbally able children with ASD who have pragmatic communication needs. [ABSTRACT FROM AUTHOR]

Background Although the UK Department of Health has advocated the involvement of service users and carers in health research for several years, there is little evidence about their contribution to the design of randomized controlled trials (RCTs). Objective To demonstrate how consulting parents about the design of a study, including which outcomes to use, led to the design and successful delivery of a RCT of osteopathy for children with cerebral palsy (CP). Design Semi-structured interviews were carried out with 20 parents of children with CP and other neurological conditions, asking them to choose between four different trial designs, to talk about noticeable changes in their child's condition and their views about payment for trial treatment. Setting and participants The parents interviewed were all members of Cerebra, a charity for 'brain-injured' children and young people. All interviews were carried out at the parents' homes. Results Parents had mixed views about possible trial designs; however, a waitlist design which allowed all children eventually to receive the treatment emerged as a clear favourite. Parents did not focus on isolated outcomes, but suggested a range of factors relevant to their child's quality of life. They expressed a clear preference for the costs of treatment to be funded by the trial. Conclusions Involvement of parents helped design a trial which was acceptable to families and addressed outcomes that mattered to them. By consulting parents about the design of the research, the subsequent trial achieved excellent recruitment and retention rates. [ABSTRACT FROM AUTHOR]