Perspectives of People with Stroke, Caregivers and Healthcare Professionals on an Adaptive mHealth Intervention for Physical Activity in the Prevention of Secondary Stroke: A Qualitative Study.

Introduction: Engaging in regular physical activity (PA) is associated with lower mortality following stroke, and PA reduces the chance of recurrent stroke. Despite recent guidelines to optimise PA following stroke, people with stroke are known to be less active than their age-matched counterparts. Given the heterogenous nature of stroke, adaptive PA interventions are recommended for people with stroke. Empirical data is lacking on adaptive PA or behavioural change interventions following stroke. Suggested strategies in the prevention of stroke recommend the use of mobile health (mHealth) interventions in the primary prevention of stroke. A structured stakeholder consultation process is key to successful implementation of complex interventions. This paper reports the findings of our consultation process to inform the development of an adaptive mHealth PA. Methods: We used a qualitative study design to explore the perspectives of key stakeholders on the development of an adaptive PA intervention delivered via mHealth post-stroke. Healthcare workers, carers and people with stroke participated in semi-structured one-to-one or focus group interviews. A reflexive thematic analysis was undertaken on transcribed interviews; key themes and sub-themes were developed using coding and summarised by two researchers, then reviewed by the full research team. Results: Twenty-eight stakeholders were interviewed and three main themes were identified; Key feature of a mHealth intervention, delivering a mHealth intervention, Challenges to development and use. There was widespread agreement across stakeholder groups that an adaptive mHealth PA intervention following stroke would be beneficial to people with stroke, following discharge from acute care. Conclusion: Our consultation supports the development of an adaptive PA programme that addresses specific impairments that can hinder exercise participation after stroke.

Closed Traumatic Avulsion of Both Flexor Digitorum Tendons: An Addition to the Leddy and Packer Classification and Review of the Literature.

Objective: We encountered the case of a patient who presented with an avulsion of both flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons from their respective insertion in the ring finger. We aim to discuss the novel treatment of this injury pattern in the context of all previously encountered cases in the literature. Materials and Methods: We examined the case of our patient with avulsion of both flexor tendons in the same finger and discuss the novel method of treatment in our case. Additionally, we performed a literature review of all previous reported cases and discuss the treatment modalities and outcomes associated with each. Results: We have shown a novel and successful treatment technique for avulsion of both the FDP and FDS tendons. We identified twelve other cases of this injury pattern and have compared all outcomes documented. Conclusion: Closed tendon avulsion of both flexor tendons in the same finger is rare. We described a case and additionally propose a modification to the flexor tendon avulsion classification to incorporate this injury pattern and aid its management.

Pilot Study of a Digital Behavioral Therapy for Overactive Bladder in Women.

IMPORTANCE: The burden and high prevalence of overactive bladder (OAB) underline the urgent need for effective treatment. This study provides an initial look at an alternative approach to behavioral therapy for overactive bladder (OAB) that is delivered as an app on a smartphone. OBJECTIVE: This study aimed to investigate feasibility, acceptability, and preliminary efficacy of a digital therapeutic for OAB. STUDY DESIGN: This was a multicentered prospective pilot study. We used a convenience sample (N = 30) from waiting lists of women referred for incontinence, excluding urinary tract infections, urinary retention, bladder pain syndrome, pelvic cancer, current pregnancy, kidney disease, dementia, stroke, and prior neuromodulation. The intervention, a smartphone app, provided an 8-week program with weekly modules combining evidence-based knowledge videos and skill-building exercises that incorporated behavioral therapy, cognitive behavioral therapy, pelvic muscle training, and general health information. Combined scores on the International Consultation on Incontinence Questionnaire was the primary outcome measure. Secondary outcomes included improvement in quality of life, based on International Consultation on Incontinence Questionnaire, a 72-hour urinary diary, and Patient Global Impression of Improvement. We evaluated usability with the Mobile Application Rating Scale. Statistical tests included Shapiro-Wilk tests and paired-sample t tests. RESULTS: Overall, 100% of participants reported a reduction in their OAB symptoms and 82% reported an improvement in quality of life. There was a significant improvement in diary parameters, including frequency (10.19-6.71 a day: SD, 1.25; P = 0.017) and incontinence (10-3.57: SD, 4.58). Participants rated the app highly on functionality, and 70% would recommend it. Patient Global Impression of Improvement improved for 72% of participants. CONCLUSIONS: This study supports the application of a digital platform to over-come the real-world barriers for first-line treatment for OAB and offers information to inform further evaluation of the safety and efficacy of the NUIG OAB App.

Sequential multiple assignment randomised trial to develop an adaptive mobile health intervention to increase physical activity in people poststroke in the community setting in Ireland: TAPAS trial protocol.

INTRODUCTION: Stroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA poststroke. To this end, we aim to use a Sequential Multiple Assignment Randomised Trial (SMART) design to develop an adaptive, user-informed mHealth intervention to improve PA poststroke. METHODS AND ANALYSIS: The components included in the 12-week intervention are based on empirical evidence and behavioural change theory and will include treatments to increase participation in Structured Exercise and Lifestyle or a combination of both. 117 participants will be randomly assigned to one of the two treatment components. At 6 weeks postinitial randomisation, participants will be classified as responders or non-responders based on participants' change in step count. Non-responders to the initial treatment will be randomly assigned to a different treatment allocation. The primary outcome will be PA (steps/day), feasibility and secondary clinical and cost outcomes will also be included. A SMART design will be used to evaluate the optimum adaptive PA intervention among community-dwelling, ambulatory people poststroke. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022). The findings will be submitted for publication and presented at relevant national and international academic conferences TRIALS REGISTRATION NUMBER: NCT05606770.

Exploring the content of the STAND-VR intervention: A qualitative interview study.

Prolonged sedentary behaviour has been identified as a potential independent contributor to a number of chronic conditions as well as mortality. The integration of digital technology into health behaviour change interventions has been shown to contribute to increases in physical activity levels, reductions in time spent sedentary, reductions in systolic blood pressure and improvements physical functioning. Recent evidence suggests that older adults could be motivated to adopt a technology such as immersive virtual reality (IVR) due to the added agency it can potentially afford them in their lives through physical and social activities offered in IVR. To date, little research has attempted to integrate health behaviour change content into an immersive virtual environment. This study aimed to qualitatively explore older adults' perspectives on the content of a novel intervention, STAND-VR, and how it could be integrated into an immersive virtual environment. This study was reported using the COREQ guidelines. Twelve participants aged between 60 and 91 years took part. Semi-structured interviews were conducted and analysed. Reflexive thematic analysis was the chosen method of analysis. Three themes were developed, "Immersive Virtual Reality: The Cover versus the Contents", "Ironing Out the (Behavioural) Details" and, "When Two Worlds Collide". These themes offer insights into how retired and non-working adults perceived IVR before and after use, how they would like to learn how to use IVR, the content and people they would like to interact with and finally, their beliefs about their sedentary activity and using IVR. These findings will contribute to future work which aims to design IVR experiences that are more accessible to retired and non-working adults, offering greater agency to take part in activities that reduce sedentary behaviour and improve associated health outcomes and, importantly, offer further opportunity to take part in activities they can ascribe greater meaning to.

Bilateral 'kissing' molars: A case report.

'Kissing molars', were described by Van Hoof in 1973 as when the occlusal surfaces of impacted molars are united by the same follicular space and the roots point in the opposite direction. There are very few published cases in the literature, and it is an extremely rare form of impaction.

The multimorbidity collaborative medication review and decision making (MyComrade) study: a pilot cluster randomised trial in two healthcare systems.

BACKGROUND: While international guidelines recommend medication reviews as part of the management of multimorbidity, evidence on how to implement reviews in practice in primary care is lacking. The MyComrade (MultimorbiditY Collaborative Medication Review And Decision Making) intervention is an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care. AIM: The pilot study aimed to assess the feasibility of a definitive trial of the MyComrade intervention across two healthcare systems (Republic of Ireland (ROI) and Northern Ireland (NI)). DESIGN: A pilot cluster-randomised controlled trial was conducted (clustered at general practice level), using specific progression criteria and a process evaluation framework. SETTING: General practices in the ROI and NI. PARTICIPANTS: Eligible practices were those in defined geographical areas who had GP's and Practice Based Pharmacists (PBP's) (in NI) willing to conduct medication reviews. Eligible patients were those aged 18 years and over, with multi morbidity and on ten or more medications. INTERVENTION: The MyComrade intervention is an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care, using a planned collaborative approach guided by an agreed checklist, within a specified timeframe. OUTCOME MEASURES: Feasibility outcomes, using pre-determined progression criteria, assessed practice and patient recruitment and retention and intervention acceptability and fidelity. Anonymised patient-related quantitative data, from practice medical records and patient questionnaires were collected at baseline, 4 and 8 months, to inform potential outcome measures for a definitive trial. These included (i) practice outcomes-completion of medication reviews; (ii) patient outcomes-treatment burden and quality of life; (iii) prescribing outcomes-number and changes of prescribed medications and incidents of potentially inappropriate prescribing; and (iv) economic cost analysis. The framework Decision-making after Pilot and feasibility Trials (ADePT) in conjunction with a priori progression criteria and process evaluation was used to guide the collection and analysis of quantitative and qualitative data. RESULTS: The recruitment of practices (n = 15) and patients (n = 121, mean age 73 years and 51% female), representing 94% and 38% of a priori targets respectively, was more complex and took longer than anticipated; impacted by the global COVID-19 pandemic. Retention rates of 100% of practices and 85% of patients were achieved. Both practice staff and patients found the intervention acceptable and reported strong fidelity to the My Comrade intervention components. Some practice staff highlighted concerns such as poor communication of the reviews to patients, dissatisfaction regarding incentivisation and in ROI the sustainability of two GPs collaboratively conducting the medication reviews. Assessing outcomes from the collected data was found feasible and appropriate for a definitive trial. Two progression criteria met the 'Go' criterion (practice and patient retention), two met the 'Amend' criterion (practice recruitment and intervention implementation) and one indicated a 'Stop - unless changes possible' (patient recruitment). CONCLUSION: The MyComrade intervention was found to be feasible to conduct within two different healthcare systems. Recruitment of participants requires significant time and effort given the nature of this population and the pairing of GP and pharmacist may be more sustainable to implement in routine practice. TRIAL REGISTRATION: Registry: ISRCTN, ISRCTN80017020 ; date of confirmation 4/11/2019; retrospectively registered.

Do resin-based sealers increase post-operative pain following root-canal treatment?

Design Systematic review. Case selection This systematic review had a focused and structured research question in term of PICO (Population, Intervention, Comparison and Outcomes). Patients included within the study were those with undergoing primary root canal treatment on a permanent tooth. The intervention was obturation with gutta percha and a resin-based sealer in comparison to obturation with gutta percha and another sealer type. The primary outcome being measured was post-operative pain incidence and/or intensity. An additional, secondary outcome, aimed to assess analgesic intake following treatment.Data analysis Data analysis was carried out by two independent reviewers using a specifically designed template which gave a concise summary of the study included within the review. The form allowed the following details to be recorded: whether a single operator completed treatment; pulpal status; irrigants used; sealer placement technique and type; obturation technique and quality; evaluation time; and outcome measures. An assessment was carried out of each study to ascertain the risk of bias which was categorised as low risk, having some areas of concerns or high risk.Six studies were included within the quantitative analysis which involved analysis of post-operative pain experiences at specified intervals. Qualitative data analysis was completed using a digital software package which allowed comparable results to be combined.Results The results from this systematic review demonstrated no significant difference in post-operative pain incidence between endodontic treatment using resin or non-resin sealers. While seven of the studies had high risk of overall bias, four were deemed low risk, and the majority of studies confirmed that there was no significant difference in the intensity of pain between the two groups. This review also confirmed that analgesic intake is not increased in patients where resin-based sealers are used when compared to non-resin sealers.Conclusion There is no significant difference in post-operative pain when resin-based root canal sealers are used when compared to other root canal sealers. For both resin and non-resin sealers, analgesics use, pain incidence post-operatively and intensity of pain reduce after 24 hours.

The MultimorbiditY COllaborative Medication Review And DEcision Making (MyComrade) study: a protocol for a cross-border pilot cluster randomised controlled trial.

BACKGROUND: While international guidelines recommend medication reviews as part of the management of multimorbidity, evidence on how to implement reviews in practice in primary care is lacking. The MultimorbiditY Collaborative Medication Review And Decision Making (MyComrade) intervention is an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care. Our aim in this pilot study is to evaluate the feasibility of a trial of the intervention with unique modifications accounting for contextual variations in two neighbouring health systems (Republic of Ireland (ROI) and Northern Ireland (NI)). METHODS: A pilot cluster randomised controlled trial will be conducted, using a mixed-methods process evaluation to investigate the feasibility of a trial of the MyComrade intervention based on pre-defined progression criteria. A total of 16 practices will be recruited (eight in ROI; eight in NI), and four practices in each jurisdiction will be randomly allocated to intervention or control. Twenty people living with multimorbidity and prescribed ≥ 10 repeat medications will be recruited from each practice prior to practice randomisation. In intervention practices, the MyComrade intervention will be delivered by pairs of general practitioners (GPs) in ROI, and a GP and practice-based pharmacist (PBP) in NI. The GPs/GP and PBP will schedule the time to review the medications together using a checklist. Usual care will proceed in practices in the control arm. Data will be collected via electronic health records and postal questionnaires at recruitment and 4 and 8 months after randomisation. Qualitative interviews to assess the feasibility and acceptability of the intervention and explore experiences related to multimorbidity management will be conducted with a purposive sample of GPs, PBPs, practice administration staff and patients in intervention and control practices. The feasibility of conducting a health economic evaluation as part of a future definitive trial will be assessed. DISCUSSION: The findings of this pilot study will assess the feasibility of a trial of the MyComrade intervention in two different health systems. Evaluation of the progression criteria will guide the decision to progress to a definitive trial and inform trial design. The findings will also contribute to the growing evidence-base related to intervention development and feasibility studies. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN80017020 . Date of confirmation is 4/11/2019.

Does the use of alcohol mouthwash increase the risk of developing oral cancer?

Design Systematic review.Case selection This study had a focused research format in terms of PICO (Population, Intervention, Comparison, Outcomes). There were no age, gender or medical conditions which restricted or excluded patients from the inclusion criteria. The intervention was the use of alcohol-based mouthwashes in comparison to the control group where no mouthwash was used. A literature search was carried out utilising three electronic databases including PubMed, Scopus and Cochrane Library. The papers included for analysis within this review were all published from 2006 onwards and animal studies, case series and case reports were excluded.Data analysis The qualitative analysis included 43,499 participants from eight papers which included two meta-analyses, one clinical trial, three case-control studies and two cohort studies, all of which fulfilled the inclusion criteria. Data were analysed by two independent reviewers who initially screened the articles and removed duplications before a second round of in-depth evaluation was conducted. A third reviewer was also included to act impartially to resolve any disagreements and reduce bias within the study. Risk of bias within studies was assessed utilising the Newcastle-Ottawa Scale (NOS) which provided a uniform approach between the reviewers. A score of 6 or greater was associated with a low level of bias.Results The primary outcome parameter measured was acetaldehyde levels in saliva and the secondary outcome factor was the risk of developing an oral cancer. The results from this review concluded that the relationship between the use of alcohol mouthwash and cancer risk is complex and influenced by multiple variables. Factors which may influence the risk of developing an oral cancer from the use of alcohol mouthwash include increased frequency of rinsing (more than three times daily), total duration of mouthwash use (>35 years), poor oral hygiene and presence of other risk factors (for example, smoking and alcohol intake).Conclusions The use of alcohol-containing mouthwashes alone (when no other risk factors are present) does not increase the risk of developing an oral cancer or lead to increased salivary acetaldehyde. However, where other risk factors for oral cancer are present, the use of an alcohol-based mouthwash may further increase this risk.

Do adjunctive antimicrobials improve the outcome of non-surgical peri-implantitis treatment?

Design This study was a single-centre, single-blind, controlled parallel group randomised control trial.Case selection Participants included those referred to The Hague Clinic for Periodontology in the Netherlands. The selection criteria included patients diagnosed with peri-implantitis, defined as marginal bone loss of >2 mm in addition to bleeding or suppuration on probing and a probing depth of >5 mm. The study was carried out over seven years and involved a control group (full mouth non-surgical peri-implantitis treatment) and a test group (non-surgical peri-implantitis treatment combined with systemic antimicrobials). Data analysis Sixty patients were recruited (30 allocated to each group) and 57 completed follow-up and were analysed according to the intention to treat principle. The patients were reviewed monthly and clinical data according to the parameters being measured were recorded. Microbiological analysis was also carried out. The power calculation was based upon the primary outcome measure of interest: bleeding on probing (BoP).Results The primary outcome parameter being measured was change in full mouth BoP and this study concluded that there were no significant differences in bleeding scores between the control and intervention at three months post-treatment. Secondary outcome parameters being measured included full mouth peri-implant and periodontal plaque scores (PS, %), clinical attachment levels, suppuration scores (SS, %), mean probing depths, mean peri-implant bone levels, change in detection frequency of periodontal pathogen species over the study duration, adverse event occurrence and need for additional surgical treatment. No significant differences were noted between the two groups for any clinical parameter.Conclusions Antimicrobial therapy does not lead to improved patient outcomes in terms of reducing microbial load and reducing pocket depth. Based on this study, there is inadequate evidence to support the use of adjunctive antimicrobials for the non-surgical treatment of peri-implantitis.

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use.

OBJECTIVE: To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients' baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes. MATERIALS AND METHODS: A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG. RESULTS: As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change -1.57 percentage points and median change -37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels. CONCLUSIONS: Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control-e.g. HbA1c and triglyceride levels-across various subgroups after controlling for baseline characteristics and concomitant medication usage.

ASCOT: Autologous Bone Marrow Stem Cell Use for Osteoarthritis of the Thumb-First Carpometacarpal Joint.

BACKGROUND: The first carpometacarpal joint (CMCJ) in the hand is a commonly affected joint by osteoarthritis. It causes significant thumb base pain, limiting functional capacity. Microfracturing and application of autologous stem cells has been performed on large joints such as the knee but has never been evaluated for use in the smaller joints in the hand. Our aim was to determine the potential benefit of microfracturing and autologous bone marrow stem cells for treatment of osteoarthritis of the first CMCJ in the hand. METHODS: All inclusion criteria were satisfied. Preoperative assessment by the surgeon, physiotherapist, and occupational therapist was performed. The first CMCJ was microfractured and the Bone Marrow Stem Cells were applied directly. Postoperatively, the patients were followed up for 1 year. RESULTS: Fifteen patients met inclusion criteria; however, 2 patients were excluded due to postoperative cellulitis and diagnosis of De Quervain's tenosynovitis. The mean scores of the 13-patient preoperative and 1 year follow-up assessments are visual analog score at rest of 3.23-1.69 (P = 0.0292), visual analog score on activity of 7.92-4.23 (P = 0.0019), range of motion 45.77o-55.15o (P = 0.0195), thumb opposition score 7.62-9.23 (P = 0.0154), Disability of the Arm, Shoulder and Hand score of 51.67-23.08 (P = 0.0065). Strength improved insignificantly from 4.7 kg preoperatively to 5.53 kg at 12 months (P = 0.1257). All patients had a positive Grind test preoperatively and a negative test after 12 months. CONCLUSIONS: This innovative pilot study is a new approach to osteoarthritis of the thumb.

WITHDRAWN: Surgery for thumb (trapeziometacarpal joint) osteoarthritis.

BACKGROUND: Surgery is used to treat persistent pain and dysfunction at the base of the thumb when conservative management, such as splinting, or medical management, such as oral analgesics, is no longer adequate in reducing disability and pain. This is an update of a Cochrane Review first published in 2005. OBJECTIVES: To assess the effects of different surgical techniques for trapeziometacarpal (thumb) osteoarthritis. SEARCH METHODS: We searched the following sources up to 08 August 2013: CENTRAL (The Cochrane Library 2013, Issue 8), MEDLINE (1950 to August 2013), EMBASE (1974 to August 2013), CINAHL (1982 to August 2013), Clinicaltrials.gov (to August 2013) and World Health Organization (WHO) Clinical Trials Portal (to August 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs where the intervention was surgery for people with thumb osteoarthritis. Outcomes were pain, physical function, quality of life, patient global assessment, adverse events, treatment failure or trapeziometacarpal joint imaging. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two review authors independently screened and included studies according to the inclusion criteria, assessed the risk of bias and extracted data, including adverse events. MAIN RESULTS: We included 11 studies with 670 participants. Seven surgical procedures were identified (trapeziectomy with ligament reconstruction and tendon interposition (LRTI), trapeziectomy, trapeziectomy with ligament reconstruction, trapeziectomy with interpositional arthroplasty (IA), Artelon joint resurfacing, arthrodesis and Swanson joint replacement). We did not find any studies that compared surgery with sham surgery or surgery with non-surgical interventions.Most included studies had an unclear risk of most biases which raises doubt about the results. No procedure demonstrated any superiority over another in terms of pain, physical function, quality of life, patient global assessment, adverse events, treatment failure (re-operation) or trapeziometacarpal joint imaging. One study demonstrated a difference in adverse events (mild-moderate swelling) between Artelon joint replacement and trapeziectomy with tendon interposition. However, the quality of evidence was very low due to a high risk of bias and imprecision of results.Low quality evidence suggests trapeziectomy with LRTI may not provide additional benefits or result in more adverse events over trapeziectomy alone. Mean pain (three studies, 162 participants) was 26 mm on a 0 to 100 mm VAS (0 is no pain) for trapeziectomy alone, trapeziectomy with LRTI reduced pain by a mean of 2.8 mm (95% confidence interval (CI) -9.8 to 4.2) or an absolute reduction of 3% (-10% to 4%). Mean physical function (three studies, 211 participants) was 31.1 points on a 0 to 100 point scale (0 is best physical function, or no disability) with trapeziectomy alone, trapeziectomy with LRTI resulted in sightly lower function scores (standardised mean difference 0.1, 95% CI -0.30 to 0.32), an equivalent to a worsening of 0.2 points (95% CI -5.8 to 6.1) on a 0 to 100 point scale (absolute decrease in function 0.03% (-0.83% to 0.88%)). Low quality evidence from four studies (328 participants) indicates that the mean number of adverse events was 10 per 100 participants for trapeziectomy alone, and 19 events per 100 participants for trapeziectomy with LRTI (RR 1.89, 95% CI 0.96 to 3.73) or an absolute risk increase of 9% (95% CI 0% to 28%). Low quality evidence from one study (42 participants) indicates that the mean scapho-metacarpal distance was 2.3 mm for the trapeziectomy alone group, trapeziectomy with LRTI resulted in a mean of 0.1 mm less distance (95% CI -0.81 to 0.61). None of the included trials reported global assessment, quality of life, and revision or re-operation rates.Low-quality evidence from two small studies (51 participants) indicated that trapeziectomy with LRTI may not improve function or slow joint degeneration, or produce additional adverse events over trapeziectomy and ligament reconstruction.We are uncertain of the benefits or harms of other surgical techniques due to the mostly low quality evidence from single studies and the low reporting rates of key outcomes. There was insufficient evidence to assess if trapeziectomy with LRTI had additional benefit over arthrodesis or trapeziectomy with IA. There was also insufficient evidence to assess if trapeziectomy with IA had any additional benefit over the Artelon joint implant, the Swanson joint replacement or trapeziectomy alone. AUTHORS' CONCLUSIONS: We did not identify any studies that compared surgery to sham surgery or to non-operative treatments. We were unable to demonstrate that any technique confers a benefit over another technique in terms of pain and physical function. Furthermore, the included studies were not of high enough quality to provide conclusive evidence that the compared techniques provided equivalent outcomes.

Surgery for thumb (trapeziometacarpal joint) osteoarthritis.

BACKGROUND: Surgery is used to treat persistent pain and dysfunction at the base of the thumb when conservative management, such as splinting, or medical management, such as oral analgesics, is no longer adequate in reducing disability and pain. This is an update of a Cochrane Review first published in 2005. OBJECTIVES: To assess the effects of different surgical techniques for trapeziometacarpal (thumb) osteoarthritis. SEARCH METHODS: We searched the following sources up to 08 August 2013: CENTRAL (The Cochrane Library 2013, Issue 8), MEDLINE (1950 to August 2013), EMBASE (1974 to August 2013), CINAHL (1982 to August 2013), Clinicaltrials.gov (to August 2013) and World Health Organization (WHO) Clinical Trials Portal (to August 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs where the intervention was surgery for people with thumb osteoarthritis. Outcomes were pain, physical function, quality of life, patient global assessment, adverse events, treatment failure or trapeziometacarpal joint imaging. We excluded trials that compared non-surgical interventions with surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two review authors independently screened and included studies according to the inclusion criteria, assessed the risk of bias and extracted data, including adverse events. MAIN RESULTS: We included 11 studies with 670 participants. Seven surgical procedures were identified (trapeziectomy with ligament reconstruction and tendon interposition (LRTI), trapeziectomy, trapeziectomy with ligament reconstruction, trapeziectomy with interpositional arthroplasty (IA), Artelon joint resurfacing, arthrodesis and Swanson joint replacement).Most included studies had an unclear risk of most biases which raises doubt about the results. No procedure demonstrated any superiority over another in terms of pain, physical function, quality of life, patient global assessment, adverse events, treatment failure (re-operation) or trapeziometacarpal joint imaging. One study demonstrated a difference in adverse events (mild-moderate swelling) between Artelon joint replacement and trapeziectomy with tendon interposition. However, the quality of evidence was very low due to a high risk of bias and imprecision of results.Low quality evidence suggests trapeziectomy with LRTI may not provide additional benefits or result in more adverse events over trapeziectomy alone. Mean pain (three studies, 162 participants) was 26 mm on a 0 to 100 mm VAS (0 is no pain) for trapeziectomy alone, trapeziectomy with LRTI reduced pain by a mean of 2.8 mm (95% confidence interval (CI) -9.8 to 4.2) or an absolute reduction of 3% (-10% to 4%). Mean physical function (three studies, 211 participants) was 31.1 points on a 0 to 100 point scale (0 is best physical function, or no disability) with trapeziectomy alone, trapeziectomy with LRTI resulted in sightly lower function scores (standardised mean difference 0.1, 95% CI -0.30 to 0.32), an equivalent to a worsening of 0.2 points (95% CI -5.8 to 6.1) on a 0 to 100 point scale (absolute decrease in function 0.03% (-0.83% to 0.88%)). Low quality evidence from four studies (328 participants) indicates that the mean number of adverse events was 10 per 100 participants for trapeziectomy alone, and 19 events per 100 participants for trapeziectomy with LRTI (RR 1.89, 95% CI 0.96 to 3.73) or an absolute risk increase of 9% (95% CI 0% to 28%). Low quality evidence from one study (42 participants) indicates that the mean scapho-metacarpal distance was 2.3 mm for the trapeziectomy alone group, trapeziectomy with LRTI resulted in a mean of 0.1 mm less distance (95% CI -0.81 to 0.61). None of the included trials reported global assessment, quality of life, and revision or re-operation rates.Low-quality evidence from two small studies (51 participants) indicated that trapeziectomy with LRTI may not improve function or slow joint degeneration, or produce additional adverse events over trapeziectomy and ligament reconstruction.We are uncertain of the benefits or harms of other surgical techniques due to the mostly low quality evidence from single studies and the low reporting rates of key outcomes. There was insufficient evidence to assess if trapeziectomy with LRTI had additional benefit over arthrodesis or trapeziectomy with IA. There was also insufficient evidence to assess if trapeziectomy with IA had any additional benefit over the Artelon joint implant, the Swanson joint replacement or trapeziectomy alone.We did not find any studies that compared any other combination of the other techniques mentioned above or any other techniques including a sham procedure. AUTHORS' CONCLUSIONS: We did not identify any studies that compared surgery to sham surgery and we excluded studies that compared surgery to non-operative treatments. We were unable to demonstrate that any technique confers a benefit over another technique in terms of pain and physical function. Furthermore, the included studies were not of high enough quality to provide conclusive evidence that the compared techniques provided equivalent outcomes.

Primary prevention of diabetic retinopathy with fibrates: a retrospective, matched cohort study.

OBJECTIVES: To compare the progression of diabetic retinopathy (DR) in people with type 2 diabetes treated with fibrates with that of non-exposed controls. DESIGN: Retrospective, matched cohort study. SETTING: UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: 5038 people with type 2 diabetes with a history of fibrate exposure but without evidence of DR were identified. Three thousand one hundred and seventy-six (63%) people could be randomly matched to one non-exposed control; of these, 2599 (81.8%) were matched without any missing blood pressure or glycated haemoglobin (HbA1c) values. MAIN OUTCOME MEASURES: The primary endpoint was first recorded DR with a secondary endpoint of all-cause mortality or first DR. Time to clinical endpoints was compared using Cox proportional hazards models. RESULTS: Mean follow-up was 5.1 and 5.0 years for fibrate-exposed and non-exposed patients, respectively. For fibrate-exposed participants, there was a reduction in DR: 33.4 events/1000 person-years vs 40.4 (p=0.002), and in death or DR: 50.6 vs 60.2 (p<0.001). For those matched with full systolic blood pressure and HbA1c data, crude event rates were 34.3 versus 43.9 for DR (p<0.001) and 51.2 vs 63.4 (p<0.001) for death or DR. Following adjustment, DR was significantly delayed for those treated with fibrates, with an adjusted HR (aHR) of 0.785 (p<0.001) for participants with complete data and an aHR of 0.802 (p<0.001) for all participants. CONCLUSIONS: The treatment with fibrates in people with type 2 diabetes was independently associated with reduced progression to a first diagnosis of DR.

Omega-3 Fatty acids and mortality outcome in patients with and without type 2 diabetes after myocardial infarction: a retrospective, matched-cohort study.

BACKGROUND: There are conflicting data regarding the benefits of omega-3 (n-3) fatty acids, most recently in patients with type 2 diabetes. OBJECTIVE: Our goal was to evaluate the impact of licensed, highly purified n-3 fatty acids on all-cause mortality after myocardial infarction (MI). METHODS: This was a retrospective, matched-cohort study using data from the General Practice Research Database. Patients initiating treatment with 1 g of n-3 fatty acids in the 90 days after first MI were identified and each matched to 4 nonexposed patients. Progression to death was compared using time-dependent Cox models to account for potential differences in exposure to other cardiovascular risk-modifying treatments. RESULTS: A total of 2466 eligible subjects exposed to n-3 fatty acids were matched. The majority of patients had concurrent treatment with lipid-lowering therapies, antihypertensives, and antiplatelets after first MI, with subjects exposed to n-3 fatty acids having a greater likelihood of concurrent exposure. For those initiating n-3 fatty acids within 90 days of first MI, the adjusted hazard ratio (aHR) was 0.782 (95% CI, 0.641-0.995; P = 0.0159); for those initiating treatment within 14 days, the aHR was 0.680 (95% CI, 0.481-0.961; P = 0.0288). In patients with type 2 diabetes at baseline, the aHRs were 0.714 (95% CI, 0.454-1.124) and 0.597 (95% CI, 0.295-1.211) when initiation was within 90 and 14 days, respectively. Use of n-3 fatty acids resulted in a consistent survival benefit under a range of scenarios quantitatively consistent with the overall effect. CONCLUSION: After MI, early treatment with licensed n-3 fatty acids was associated with improvement in all-cause mortality in patients with and without type 2 diabetes, against a background of contemporary cardiovascular risk-modifying treatments.

Gp91(phox) contributes to the development of experimental inflammatory bowel disease.

Inflammatory bowel disease (IBD) is related to dysfunction of intestinal immunity. Neutrophils have an important role in innate immunity via the oxidative burst, using the p47phox- and gp91(phox)-containing NAD(P)H oxidase known as Nox2. In dextran sulphate sodium (DSS)-induced colitis, no significant difference in inflammation between p47(phox-/-) and wild-type (WT) mice was reported, but there was improved endothelium-dependent arteriolar dilation in gp91(phox-/-) mice, compared with that in WT mice. Gp91(phox) and p47 (phox) are not only essential components of phagocyte Nox2, but also have roles in other enzymes. Thus the differences in response of their respective gene knockout mice to DSS challenge are not completely unexpected, but need further investigation. The clinicopathological changes and immunological responses to DSS challenge have not been fully described in gp91(phox-/-) mice. Thus we treated WT and gp91(phox-/-) mice with 2.5% DSS for 7 days. The gp91(phox-/-) mice developed less severe colitis than WT mice following DSS treatment, reflected by a smaller body weight loss, less rectal bleeding and fewer histopathological changes. Less colonic myeloperoxidase was observed in gp91(phox-/-), compared with WT mice, following DSS challenge, correlating with interleukin (IL)-6 production. IL-10 was upregulated in both gp91(phox-/-) and WT mice, but was significantly higher in the latter, following 7 days DSS challenge. These results suggest that gp91(phox-/-) mice are less susceptible to acute DSS-induced colitis, possibly because of a reduced oxidative burst in the intestine and, consequently, less tissue damage.

An evaluation of the cost-effectiveness of rituximab in combination with chemotherapy for the first-line treatment of follicular non-Hodgkin's lymphoma in the UK.

OBJECTIVES: In this study, the cost-effectiveness of rituximab was evaluated in comparison with commonly used chemotherapy regimens for patients with advanced follicular lymphoma (FL), from the perspective of the UK National Health Service (NHS). METHODS: Results from four randomized controlled trials comparing the addition of rituximab to chemotherapy regimens: mitoxantrone, chlorambucil, and prednisolone (MCP); cyclophosphamide, vincristine, and prednisolone (CVP); cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP); or cyclophosphamide, etoposide, doxorubicin, prednisolone, and interferon alpha (CHVP + IFNalpha) versus chemotherapy alone were used to develop a Markov model. The rates of disease progression and the duration of treatment effect were obtained from the trial data. Treatments were compared in two ways: 1) an individual comparison of rituximab + chemotherapy versus chemotherapy and 2) a multiple treatment comparison using league tables. Economic and clinical outcomes (quality-adjusted life-years (QALYs)) were estimated over patient lifetimes and discounted at 3.5% per annum. RESULTS: In the individual comparison, the addition of rituximab increased QALYs by (mean, 95% confidence interval) 1.174 (1.02-1.30), 0.909 (0.79-1.01), 0.823 (0.71-0.91), and 0.453 (0.40-0.50) for MCP, CVP, CHOP, and CHVP, respectively, compared with chemotherapy alone. The incremental costs per QALY gained were pound7474, pound8621, pound10,732, and pound8551, respectively. Sensitivity analyses indicated that rituximab plus chemotherapy was a cost-effective treatment option, with incremental cost-effectiveness ratios below a threshold of pound30,000 per QALY gained. When compared across the chemotherapy regimens, rituximab plus MCP appeared to be the single most cost-effective treatment option, but further randomized trials are required to substantiate this. CONCLUSIONS: The addition of rituximab to chemotherapy in advanced FL was found to be highly cost-effective in the UK.