Search

Background Vaccines may reduce antibiotic use and the development of resistance. Objectives To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. Data sources Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. Study eligibility criteria Randomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018. Participants Any population. Interventions Vaccines versus placebo, no vaccine or another vaccine. Methods Titles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. Results In all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0–38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54–0·70) and probably reduce community antibiotic use in children aged 3–15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58–0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87–0·99) and reduces illness episodes requiring antibiotics in children aged 12–35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75–0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. Conclusions The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO registration CRD42018103881.

Non-emergent visits to emergency departments by uninsured patients impose unnecessary costs on both patients and safety-net institutions. We evaluated the health and economic impacts of providing free, walk-in care to low-income, uninsured adults-most of them Hispanic-at a free clinic between January 2013 and December 2016. Providing access to health care services for uninsured patients at Clínica Esperanza/Hope Clinic reduced emergency department expenditures in Rhode Island by approximately $448,876 (range: $410,377-$487,375) annually and may have also reduced future healthcare costs for this population by more than $48 million ($12,034,469 annually) over the four-year evaluation period. For every $1 in funding for walk-in clinic operation, delivering free care provided a return on investment of $71.18 (range: $70.95-71.40) in healthcare value. Providing access to non-emergent walk-in care at the more than 12,000 free healthcare clinics nationwide may save billions in ED costs while improving the health of uninsured individuals.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.

Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable.To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia.This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders.There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were10.6 mg/L (39% vs. 13%; P = 0.006) and AUC410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity.Failure was more common with troughs10.6 mg/L or AUC410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

Purpose The objective of this study was to evaluate the short-term hemodynamic effects as well as vasopressor requirements with concomitant vasopressin (AVP) and hydrocortisone (HCT) compared to either agent alone in refractory septic shock. Materials and methods This was a retrospective, cohort study conducted in adult septic shock patients. Patients received continuous infusion AVP at 0.04 units/min and/or HCT 200–300 mg intravenous daily in divided doses for refractory septic shock. Refractory septic shock was defined as systolic or mean blood pressure (MAP) of Results A total of 300 patients were evaluated. The rate of achieving a “response” (norepinephrine dose reduction by ≥ 50% without any decrease in MAP) at 4 h from baseline was significantly higher in patients receiving concomitant AVP/HCT (88.5%) compared to HCT alone (62.3%) or AVP alone (72.9%) (p = 0.0005). The AVP/HCT group had higher “response” rates over the HCT and AVP monotherapy groups at 12 (p = 0.052) and 24 h (p = 0.036). Multivariate regression showed combination therapy to be independently associated with response at 4 h. Conclusions Concomitant AVP and HCT was associated with an immediate, additive catecholamine-sparing effect over either agent alone in patients with refractory septic shock.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist–led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use ( P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively ( P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist–led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Background Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered to women for whom conservative treatments have failed. Midurethral tapes have superseded colposuspension because cure rates are comparable and recovery time is reduced. However, some women will not be cured after midurethral tape surgery. Currently, there is no consensus on how to manage the condition in these women.This is an update of a Cochrane Review first published in 2013. Objectives To assess the effects of interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women; and to summarise the principal findings of economic evaluations of these interventions. Search methods We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 9 November 2018). We also searched the reference lists of relevant articles. Selection criteria We included randomised and quasi-randomised controlled trials in women who had recurrent stress urinary incontinence after previous minimally invasive midurethral tape surgery. We included conservative, pharmacological and surgical treatments. Data collection and analysis Two review authors checked the abstracts of identified studies to confirm their eligibility. We obtained full-text reports of relevant studies and contacted study authors directly for additional information where necessary. We extracted outcome data onto a standard proforma and processed them according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. Main results We included one study in this review. This study was later reported in an originally unplanned secondary analysis of 46 women who underwent transobturator tape for recurrent SUI after one or more previous failed operations. We were unable to use the data, as they were not presented according to the nature of the first operation.We excluded 12 studies, five because they were not randomised controlled trials (RCTs) and four because previous incontinence surgery was not performed using midurethral tape. We considered a further three to be ineligible because neither the trial report nor personal communication with the trialists could confirm whether any of the participants had previously undergone surgery with tape.We had also planned to develop a brief economic commentary summarising the principal findings of relevant economic evaluations but supplementary systematic searches did not identify any such studies. Authors' conclusions There were insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress incontinence after failed midurethral tape surgery. No published papers have reported exclusively on women whose first operation was a midurethral tape. Evidence from further RCTs and economic evaluations is required to address uncertainties about the effects and costs of these treatments.

Background: Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). The clinical utility of the Sheiner-Tozer equation for adjusting total phenytoin levels for hypoalbuminemia remains controversial. Objective: The purpose of this study was to evaluate the correlation of this formula in predicting phenytoin serum concentrations. Methods: A retrospective cohort study was conducted in the adult ICU between January 1, 2010, and June 21, 2013. Patients meeting the following study criteria were included: age ≥18 years, admission to the ICU, simultaneously drawn total and free serum phenytoin concentrations with albumin ≤48 hours of phenytoin draws. Study end points were the correlation as well as the level of agreement in the interpretation of the free and adjusted phenytoin concentrations using the Sheiner-Tozer formula in critically ill patients with hypoalbuminemia. Results: A total of 238 patients were analyzed. Mean adjusted total phenytoin and free levels were 16.1 ± 8.1 and 1.5 ± 0.8 µg/mL, respectively ( r = 0.817; P < 0.001). Absolute agreement with level interpretation between adjusted total phenytoin and free levels was 77% (κ = 0.633; P < 0.001). Adjusted phenytoin serum concentrations more frequently overestimated the free level. Conclusions: There is a significant correlation between free and adjusted total phenytoin levels using the Sheiner-Tozer equation in critically ill patients. However, disagreement was noted with interpretation, primarily because of the adjusted concentration overestimating the free level. This imprecision may lead to inaccurate decision making regarding the management of phenytoin in this patient population. Thus, free phenytoin levels should be utilized.

Background:Previous studies have demonstrated that hip arthroscopy is an effective treatment for symptomatic femoroacetabular impingement (FAI) in professional athletes across a variety of sports. However, the return-to-play rates and postoperative performance of elite basketball players after hip arthroscopy are currently unknown.Purpose:To determine return-to-play rates and postoperative performance among professional basketball athletes after hip arthroscopy.Study Design:Case series; Level of evidence, 3.Methods:Eighteen professional basketball players underwent hip arthroscopy (24 hips) for symptomatic FAI between 2001 and 2016 by a single surgeon. Return to play was defined as competing in a single professional game of equal level after surgery. Data were retrospectively obtained for each player from basketball-reference.com , ESPN.com , eurobasket.com, and individual team websites. Matched controls were selected from the websites to compare performances.Results:The mean age at the time of surgery was 25.6 years, and the mean body mass index was 24.4 kg/m2. All players returned to their previous levels of competition, with a mean number of 4 seasons played after surgery (median, 3; range, 1-12). The mean ± SD time between the date of surgery and return to a professional game was 7.1 ± 4.4 months. There was no change in player efficiency rating when pre- and postinjury performance were compared. When compared with controls, players undergoing surgery also had no significant decline in player efficiency rating.Conclusion:Elite basketball athletes who undergo hip arthroscopy for the treatment of FAI return to their presurgical levels of competition at a high rate. These athletes demonstrate no significant overall decrease in performance upon their return to play.

Purpose The objective of this study was to evaluate AKI incidence with concomitant vancomycin and piperacillin/tazobactam (PTZ) compared to vancomycin and cefepime (FEP) in critically ill patients. Materials and methods A retrospective, cohort study was conducted in adult critically ill patients from January 1, 2014 to December 31, 2017. The primary aim was to compare the incidence of AKI during concomitant therapy or until hospital discharge. Secondary analyses included AKI severity, time to AKI as well as recovery, and clinical outcomes. Results Overall, 333 patients were evaluated. The AKI rate in the vancomycin/PTZ group and vancomycin/FEP group were similar (19.5% vs. 17.3%, respectively, p = .612). Renal replacement therapy (RRT) was initiated in 10.0% and 3.8% administered vancomycin/PTZ and vancomycin/FEP groups, respectively (p = .04). Multivariate regression found vancomycin/PTZ was not associated with an increased risk of developing AKI although the presence of shock was identified as an independent risk factor (odds ratio, 3.22; 95% CI, 1.66–6.26). No significant differences in hospital or ICU length of stay or in-hospital mortality were observed between study groups. Conclusions Concomitant PTZ and vancomycin in ICU patients was not associated with an increased risk of developing AKI compared to FEP and vancomycin combinations. More patients administered vancomycin/PTZ received RRT.

Two-stage exchange arthroplasty is the preferred treatment for chronic periprosthetic joint infection following total hip arthroplasty (THA). These patients are at high risk of substantial blood loss and perioperative blood transfusion. Our study aimed at determining risk factors for blood transfusion during a 2-stage exchange for infected THA.Medical records of 297 patients with infected THA who underwent 2-stage exchange arthroplasty from 1997 to 2016 were reviewed. Blood loss was calculated using a validated formula. Transfusion data, clinical information, and operative data were gathered to determine predictors of blood loss and risk factors for perioperative allogeneic blood transfusion.Calculated blood loss was significantly higher during reimplantation than resection arthroplasty (5156.0 ± 3402 mL vs 3706.9 ± 2148 mL; P.0001). Blood transfusion was needed in 81% after resection and 81.1% after reimplantation. Allogeneic blood transfusion averaged 3.6 ± 1.8 units for stage 1 and 4.2 ± 2.9 units for stage 2 (P = .0066). Patient characteristics that increased the likelihood for perioperative blood transfusions were increasing preoperative international normalized ratio, type 2 diabetes, current smoking, age, and transfusion requirement in the first stage. Tranexamic acid usage was associated with decreased blood loss.Patients with periprosthetic joint infection following THA have significant blood loss during both stages of exchange arthroplasty, especially reimplantation. Hematological optimization should be considered in all patients requiring a transfusion after the first stage, as these patients are at greater risk of requiring transfusion after the second stage. The use of tranexamic acid dramatically decreases the risk of requiring a transfusion in both stages and should be more ubiquitously incorporated into blood management protocols.

Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population.Multicenter, observational study: Medical ICUs at three academic medical centers.Adult patients (age ≥ 18 yr old) receiving medication therapy.All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions.Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154).Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

There is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.Our objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.We performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.The literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer's and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer's and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.ChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects.

Adverse events in the intensive care unit (ICU) may be associated with several possible causes, so determining a drug-related causal assessment is more challenging than in general ward patients. Therefore, the hypothesis was that automated trigger alerts may perform differently in various patient care settings. The purpose of this study was to compare the frequency and type of clinically significant automated trigger alerts in critically ill and general ward patients as well as evaluate the performance of alerts for drug-related hazardous conditions (DRHCs).A retrospective cohort study was conducted in adult ICU and general ward patients at three institutions (academic, community, and rural hospital) in a health system. Automated trigger alerts generated during two nonconsecutive months were obtained from a centralized database. Pharmacist responses to alerts and prescriber response to recommendations were evaluated for all alerts. A clinical significant event was defined as an actionable intervention requiring drug therapy changes that the pharmacist determined to be appropriate for patient safety and where the physician accepted the pharmacist's recommendation. The positive predictive value (PPV) was calculated for each trigger alert considered a DRHC (i.e., abnormal laboratory values and suspected drug causes).A total of 751 alerts were generated in 623 patients during the study period. Pharmacists intervened on 39.8 and 44.8 % alerts generated in the ICU and general ward, respectively. Overall, the physician acceptance rate of approximately 90 % was comparable irrespective of patient care setting. Therefore, the number of clinically significant alerts was 88.9 and 83.4 % for the ICU and non-ICU, respectively. The types of drug therapy changes were similar between settings. The PPV of alerts identifying a DRHC was 0.66 in the ICU and 0.76 in general ward patients.The number and type of clinically significant alerts were similar irrespective of patient population, suggesting that the alerts may be equally as beneficial in the ICU population, despite the challenges in drug-related event adjudication. An opportunity exists to improve the performance of alerts in both settings, so quality improvement programs for measuring alert performance and making refinements is needed.

BackgroundThe position of invasive urodynamic testing in the diagnostic pathway for urinary incontinence (UI) is unclear. Systematic reviews have called for further trials evaluating clinical utility, although a preliminary feasibility study was considered appropriate.ObjectivesTo inform the decision whether or not to proceed to a definitive randomised trial of invasive urodynamic testing compared with clinical assessment with non-invasive tests, prior to surgery in women with stress UI (SUI) or stress predominant mixed UI (MUI).DesignA mixed-methods study comprising a pragmatic multicentre randomised pilot trial; economic evaluation; survey of clinicians’ views about invasive urodynamic testing; qualitative interviews with clinicians and trial participants.SettingUrogynaecology, female urology and general gynaecology units in Newcastle, Leicester, Swansea, Sheffield, Northumberland, Gateshead and South Tees.ParticipantsTrial recruits were women with SUI or stress predominant MUI who were considering surgery after unsuccessful conservative treatment. Relevant clinicians completed two online surveys. Subsets of survey respondents and trial participants took part in separate qualitative interview studies.InterventionsPilot trial participants were randomised to undergo clinical assessment with non-invasive tests (control arm); or assessment as controls, plus invasive urodynamic testing (intervention arm).Main outcome measuresConfirmation that units can identify and recruit eligible women; acceptability of investigation strategies and data collection tools; acquisition of outcome data to determine the sample size for a definitive trial. The proposed primary outcome for the definitive trial was International Consultation on Incontinence Modular Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) (total score) 6 months after surgery or the start of non-surgical treatment; secondary outcomes included: ICIQ-FLUTS (subscales); ICIQ Urinary Incontinence Short Form; ICIQ Lower Urinary Tract Symptoms Quality of Life; Urogenital Distress Inventory; EuroQol-5D; costs, quality-adjusted life-years (QALYs) and incremental cost per QALY, Short Form 12; 3-day bladder diary.ResultsOf 284 eligible women, 222 (78%) were recruited; 165/219 (75%) returned questionnaires at baseline and 125/200 (63%) who were sent questionnaires at follow-up. There were few missing data items in returned questionnaires, with individual outcome scales calculable for 81%–94%. Most women underwent surgery; management plans were changed in 19 (19%) participants following invasive urodynamic testing. Participant Costs Questionnaires were returned by 53% 6 months after treatment; complete data to undertake cost–utility analysis were available in 27% (intervention) and 47% (control). While insufficient to recommend changes in practice, the results suggest further research would be valuable. All clinicians responding to the survey had access to invasive urodynamic testing, and most saw it as essential prior to surgery in women with SUI with or without other symptoms; nevertheless, 70% considered the research question underlying INVESTIGATE important and most were willing to randomise patients in a definitive trial. Participants interviewed were positive about the trial and associated documentation; the desire of some women to avoid invasive urodynamic testing contrasted with opinions expressed by clinicians through both survey and interview responses.ConclusionsAll elements of a definitive trial and economic evaluation were rehearsed; several areas for protocol modification were identified. Such a trial would require to 400–900 participants, depending on the difference in primary outcome sought.Future workA definitive trial of invasive urodynamic testing versus clinical assessment prior to surgery for SUI or stress predominant MUI should be undertaken.Trial registrationCurrent Controlled Trials ISRCTN71327395.FundingThe National Institute for Health Research Health Technology Assessment programme.

Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between patients. We previously used an autoantibody transgenic mouse reporter system to examine the effect of different autoimmune backgrounds on B-cell tolerance, failure of which is a fundamental defect in lupus. We identified a defect consistent with reversible anergy induced by endotoxin stimulation of B cells from Ig transgenic New Zealand Black (NZB) mice. Herein we report that the tolerance defect is revealed by TLR7 and TLR9 as well as TLR4 ligands, with additive effect, and is partially reversed by Mek inhibition. Gene expression analysis reveals significant differences in transcription of multiple TLR pathway genes and ptpn22 in stimulated NZB compared to B6 B cells. Additionally, the defect is detected in Ig transgenic NZB F1 hybrid strains (NZBxNZW)F1 and (B6xNZB)F1. These results implicate an inherited defect wherein NZB anergic B cells maintain coordinated TLR/BCR signaling that permits autoantibody production. Agents targeting these pathways may have therapeutic benefit in the subset of lupus patients that manifest similar defects in B-cell regulation.

Background Self-monitoring of blood glucose (SMBG) is recommended as a key component of the management plan for diabetes therapy during pregnancy. No existing systematic reviews consider the benefits/effectiveness of various techniques of blood glucose monitoring on maternal and infant outcomes among pregnant women with pre-existing diabetes. The effectiveness of the various monitoring techniques is unclear. Objectives To compare techniques of blood glucose monitoring and their impact on maternal and infant outcomes among pregnant women with pre-existing diabetes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016), searched reference lists of retrieved studies and contacted trial authors. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing techniques of blood glucose monitoring including SMBG, continuous glucose monitoring (CGM) or clinic monitoring among pregnant women with pre-existing diabetes mellitus (type 1 or type 2). Trials investigating timing and frequency of monitoring were also included. RCTs using a cluster-randomised design were eligible for inclusion but none were identified. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. Main results This review update includes at total of 10 trials (538) women (468 women with type 1 diabetes and 70 women with type 2 diabetes). The trials took place in Europe and the USA. Five of the 10 included studies were at moderate risk of bias, four studies were at low to moderate risk of bias, and one study was at high risk of bias. The trials are too small to show differences in important outcomes such as macrosomia, preterm birth, miscarriage or death of baby. Almost all the reported GRADE outcomes were assessed as being very low-quality evidence. This was due to design limitations in the studies, wide confidence intervals, small sample sizes, and few events. In addition, there was high heterogeneity for some outcomes. Various methods of glucose monitoring were compared in the trials. Neither pooled analyses nor individual trial analyses showed any clear advantages of one monitoring technique over another for primary and secondary outcomes. Many important outcomes were not reported. 1. Self-monitoring versus standard care (two studies, 43 women): there was no clear difference for caesarean section (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.40 to 1.49; one study, 28 women) or glycaemic control (both very low-quality), and not enough evidence to assess perinatal mortality and neonatal mortality and morbidity composite. Hypertensive disorders of pregnancy, large-for-gestational age, neurosensory disability, and preterm birth were not reported in either study. 2. Self-monitoring versus hospitalisation (one study, 100 women): there was no clear difference for hypertensive disorders of pregnancy (pre-eclampsia and hypertension) (RR 4.26, 95% CI 0.52 to 35.16; very low-quality: RR 0.43, 95% CI 0.08 to 2.22; very low-quality). There was no clear difference in caesarean section or preterm birth less than 37 weeks' gestation (both very low quality), and the sample size was too small to assess perinatal mortality (very low-quality). Large-for-gestational age, mortality or morbidity composite, neurosensory disability and preterm birth less than 34 weeks were not reported. 3. Pre-prandial versus post-prandial glucose monitoring (one study, 61 women): there was no clear difference between groups for caesarean section (RR 1.45, 95% CI 0.92 to 2.28; very low-quality), large-for-gestational age (RR 1.16, 95% CI 0.73 to 1.85; very low-quality) or glycaemic control (very low-quality). The results for hypertensive disorders of pregnancy: pre-eclampsia and perinatal mortality are not meaningful because these outcomes were too rare to show differences in a small sample (all very low-quality). The study did not report the outcomes mortality or morbidity composite, neurosensory disability or preterm birth. 4. Automated telemedicine monitoring versus conventional system (three studies, 84 women): there was no clear difference for caesarean section (RR 0.96, 95% CI 0.62 to 1.48; one study, 32 women; very low-quality), and mortality or morbidity composite in the one study that reported these outcomes. There were no clear differences for glycaemic control (very low-quality). No studies reported hypertensive disorders of pregnancy, large-for-gestational age, perinatal mortality (stillbirth and neonatal mortality), neurosensory disability or preterm birth. 5.CGM versus intermittent monitoring (two studies, 225 women): there was no clear difference for pre-eclampsia (RR 1.37, 95% CI 0.52 to 3.59; low-quality), caesarean section (average RR 1.00, 95% CI 0.65 to 1.54; I² = 62%; very low-quality) and large-for-gestational age (average RR 0.89, 95% CI 0.41 to 1.92; I² = 82%; very low-quality). Glycaemic control indicated by mean maternal HbA1c was lower for women in the continuous monitoring group (mean difference (MD) -0.60 %, 95% CI -0.91 to -0.29; one study, 71 women; moderate-quality). There was not enough evidence to assess perinatal mortality and there were no clear differences for preterm birth less than 37 weeks' gestation (low-quality). Mortality or morbidity composite, neurosensory disability and preterm birth less than 34 weeks were not reported. 6. Constant CGM versus intermittent CGM (one study, 25 women): there was no clear difference between groups for caesarean section (RR 0.77, 95% CI 0.33 to 1.79; very low-quality), glycaemic control (mean blood glucose in the 3rd trimester) (MD -0.14 mmol/L, 95% CI -2.00 to 1.72; very low-quality) or preterm birth less than 37 weeks' gestation (RR 1.08, 95% CI 0.08 to 15.46; very low-quality). Other primary (hypertensive disorders of pregnancy, large-for-gestational age, perinatal mortality (stillbirth and neonatal mortality), mortality or morbidity composite, and neurosensory disability) or GRADE outcomes (preterm birth less than 34 weeks' gestation) were not reported. Authors' conclusions This review found no evidence that any glucose monitoring technique is superior to any other technique among pregnant women with pre-existing type 1 or type 2 diabetes. The evidence base for the effectiveness of monitoring techniques is weak and additional evidence from large well-designed randomised trials is required to inform choices of glucose monitoring techniques.

Our aim was to evaluate the use of very-low-dose methadone with haloperidol in the acute-care setting.We reviewed the records of 735 hospitalized patients receiving a palliative care consultation between 2011 and 2014. All patients with pain on opiates were offered conversion to methadone, 2.5 mg/day to 15 mg/day, in conjunction with scheduled haloperidol. Additional doses of haloperidol or short-acting opiates were given as needed for pain. Patients receiving an opiate at a morphine-equivalent daily dose (MEDD) of ≥40 mg had pain scores assessed daily, before and after conversion. Descriptive statistics were used to summarize the results.Forty-three patients underwent conversion from another opiate (median MEDD, 78.5 mg) to methadone (median daily dose, 5 mg) and haloperidol (median daily dose, 1.5 mg). The median pain score was 5 in the week prior to conversion, 1 in week 1 after conversion (p0.001 for difference), and zero in week 2. Similar results were seen for patients with cancer and noncancer diagnoses and for those with the highest and lowest initial opiate doses.The use of very-low-dose methadone in conjunction with haloperidol in the acute-care setting resulted in improved pain control after conversion from typical opiates.

Anemia is common in several patient populations, including those with chronic kidney disease, cancer, and HIV/AIDS, and may require treatment with erythropoietin-stimulating agents (ESAs). Given the potential risks of the ESA, epoetin, and the significant costs associated with this agent, a large teaching medical institution developed a the drug-utilization management program using evidence-based guidelines on appropriate use.This study was designed to determine the clinical and financial impact of the drug-utilization management program.This retrospective cohort study was conducted at the medical institution that implemented the program using clinical pharmacists. Patients were included if epoetin was administered during their hospital stay (evaluation period, December 1, 2010, to December 31, 2011). The rate of inappropriate epoetin prescribing and the economic impact of guideline implementation were evaluated using comparisons of data from cohorts prescribed epoetin before and after guideline implementation.Data from 796 patients were included in the analyses (pre-implementation, 496; post-implementation, 300). The proportion of patients prescribed epoetin was significantly smaller after guideline implementation (2.4% vs 1.6%; P0.001). The reduction in the total number of epoetin units administered was 45%. The significant reduction (25%) in inappropriate prescribing after guideline implementation was primarily attributed to a 17% decrease in epoetin use in nonspecific anemia. The reduction in inappropriate epoetin prescribing translated into a 23.8% reduction in costs (P0.001) associated with inappropriate epoetin use. The estimated annual cost-savings of this program was $198,352 ($16,529/mo).The implementation of a drug-utilization management program using clinical pharmacists who evaluated epoetin was associated with a decrease in inappropriate epoetin prescribing and with significant cost-savings.

Living organisms follow a circadian rhythm in which physiological processes such as hormonal secretion, metabolism, heart rate, and renal output are affected by the time of day. Chronotherapy coordinates drug delivery with the circadian rhythm to enhance effectiveness and mitigate adverse effects and is achieved by delivering a drug when the system is most susceptible. Cancer is a chronotherapeutic disorder. Cancer treatment requires high doses of intravenous medication to kill cancerous cells; however, normal cells are also killed, creating intolerable side effects. This review shows that chronotherapy can play a vital role in the quality of life and survival rate for oncology patients.

The optimal surgical technique for a distal biceps tendon rupture repair still remains controversial. Current biomechanical evidence shows Endobutton fixation to have the highest load-to-failure testing, but clinical results of this are limited. The purpose of this study was to compare patient-oriented functional outcome between a modified Boyd-Anderson two-incision technique and repair with a single-incision Endobutton technique.All patients who underwent distal biceps tendon repair with a two-incision or Endobutton technique between 2000 and 2010 with two-year follow-up at our institution were identified. Their clinical, operative, and follow-up data was collected and analyzed. The primary outcome was a patient-oriented functional outcome measure (Disabilities of the Arm, Shoulder, and Hand: DASH). Secondary outcomes were evaluated using a subjective questionnaire.Thirty-three patients were repaired with the two-incision technique and twenty-five patients had a repair with a single incision Endobutton technique. All patients receiving the two-incision repair were male, while there were 2 females who had an Endobutton procedure. There was no significant difference between the two-incision and the Endobutton groups in regards to mean DASH score (6.31 versus 5.91, p = 0.697), mean Work DASH score (10.49 versus 0.93, p = 0.166), and mean Sports DASH score (10.54 versus 9.56, p = 0.987). Regardless of technique, most patients were "extremely satisfied" (n = 42, or 72.41%) or "satisfied" (n = 10, or 17.24%) postoperatively, and returned to pre-operative activity in approximately 6 months (6.87 months versus 6.82 months, respectively) (p = 0.457). There was no significant difference in the prevalence of complications (39.39% versus 32.0%, respectively for two incision versus single incision) (p = 0.594).Patients from both surgical groups were satisfied with their post-operative function and had similar functional outcomes and complication rates. Both surgical techniques for distal biceps tendon repair are effective and are similarly safe methods of treatment.

Introduction Understanding the views of the public is essential if generally acceptable policies are to be devised that balance research access to general practice patient records with protection of patients9 privacy. However, few large studies have been conducted about public attitudes to research access to personal health information. Methods A mixed methods study was performed. Informed by focus groups and literature review, a questionnaire was designed which assessed attitudes to research access to personal health information and factors that influence these. A postal survey was conducted of an electoral roll-based sample of the adult population of Ireland. Results Completed questionnaires were returned by 1575 (40.6%). Among the respondents, 67.5% were unwilling to allow GPs to decide when researchers could access identifiable personal health information. However, 89.5% said they would agree to ongoing consent arrangements, allowing the sharing by GPs of anonymous personal health information with researchers without the need for consent on a study-by-study basis. Increasing age (by each 10-year increment), being retired and primary level education only were significantly associated with an increased likelihood of agreeing that any personal health information could be shared on an ongoing basis: OR 1.39 (95% CI 1.18 to 1.63), 2.00 (95% CI 1.22 to 3.29) and 3.91 (95% CI 1.95 to 7.85), respectively. Conclusions Although survey data can be prone to response biases, this study suggests that prior consent agreements allowing the supply by GPs of anonymous personal health information to researchers may be widely supported, and that populations willing to opt in to such arrangements may be sufficiently representative to facilitate valid and robust consent-dependent observational research.

The purpose of our study was to measure patient size on CT images as a function of age at a large tertiary care children's hospital to develop current patient size data for modeling optimal x-ray exposure factors in children.Anteroposterior and transverse dimensions of the head, thorax, abdomen, and pelvis were measured on CT examinations of pediatric patients less than 21 years old performed between June and November 2007. Patients with diseases that could affect measurements were excluded. From 1,009 patients, 336 examinations of each of four body regions were selected; 2,688 measurements were made and separated into 21 groups. Statistical model building and prediction equations were established for each region and 95% prediction intervals were used for analyses.Rapid growth of the head occurred from birth to approximately 2 years followed by a gradual plateau until 21 years. The thoracic, abdominal, and pelvic regions showed a linear relationship between age and size. Fitted equations showed transverse trunk measurements increased more rapidly than anteroposterior measurements. The anteroposterior trunk size growth rate was relatively region independent; transverse pelvic dimensions grew more rapidly than thoracic or abdominal regions. There was a broad overlap of predicted patient size ranges as a function of age within each region. Excellent interobserver agreement was measured by Pearson's correlation coefficient (r) (all p0.0001).Fitted average patient sizes are age dependent; however, predicted individual patient size does not correlate well with age. Our study suggests that pediatric patient body size should be determined for individual patients before performing diagnostic imaging procedures that entail radiation risks.

Prenatal alcohol exposure can lead to a wide range of adverse effects on a developing fetus. As a whole, these teratogenic outcomes are generally known as fetal alcohol spectrum disorders, the most severe of which is fetal alcohol syndrome (FAS). Clinically, children diagnosed with FAS vary greatly in their presentation of symptoms, likely due to the amount of alcohol and timing of exposure, as well as maternal and genetic influences. All these factors play a role in determining the mechanisms through which alcohol damages a developing brain, the details of which are still largely unknown. However, continuing research and recent developments have provided promising results that may lead to screening mechanisms and treatment therapies for children with FAS. Here we review the teratogenic effects of alcohol, strategies for detecting maternal alcohol consumption, identification of fetal biological markers, and prevention methods for FAS.

Background Patients with mildly abnormal or equivocal myocardial perfusion imaging (MPI) scans undergo diagnostic angiography or receive medical management. However, current guidelines mandate different treatment goals for patients with known coronary artery disease (CAD), and catheterization is often required. Coronary computed tomography angiography (CCTA) may be an effective alternative to catheterization for patients at intermediate risk for CAD. Objectives The purpose of this study was to analyze the cost implications of CCTA before catheterization in patients with mildly abnormal or equivocal MPI scans. Methods Patients (n = 206) with mildly abnormal or equivocal MPI scans underwent 64-detector CCTA instead of catheterization at the discretion of a treating physician. Studies were evaluated by a trained reader, and results were classified as “no evident CAD,” “nonobstructive CAD,” or “potentially obstructive CAD.” Cost data were analyzed based on actual reimbursements for CT angiography and cardiac catheterization. We modeled the costs of two clinical approaches. “Selective catheterization” involved catheterization only if CCTA showed potentially obstructive CAD. “Immediate catheterization” considered catheterization for all patients in the cohort. Sensitivity analysis was performed on multiple variables. Results Thirty-two percent of patients had potentially obstructive plaque on CTA. Selective catheterization saves $1454 per patient. Sensitivity analysis revealed cost savings to be preserved even if up to 81.5% of the patient cohort undergoes catheterization, as well as across wide ranges of procedural costs. Conclusion A strategy that uses CCTA as a gatekeeper to catheterization is cost saving as opposed to initial catheterization for patients with equivocal or mildly abnormal myocardial perfusion scans.

Background. The importance of chronic kidney disease as an independent risk factor for morbidity and mortality in patients with cardiovascular disease in the community is not widely recognized. Methods. A retrospective cohort study based in the West of Ireland followed a randomized practicebased sample of patients with cardiovascular disease. A database of 1609 patients with established cardiovascular disease was established in 2000. This was generated from a randomized sample of 35 general practices in the West of Ireland. The primary endpoint was a cardiovascular composite endpoint, which included death from a cardiovascular cause or any of the cardiovascular events of myocardial infarction (MI), heart failure, peripheral vascular disease and stroke. The secondary endpoint was death from any cause. Results. Of the original community-based cohort of 1609 patients with cardiovascular disease, 1272 (79%) had one or more serum creatinine measurements during the study period and 31 (1.9%) patients were lost to follow-up. Median follow-up was 2.90 years (SD 1.47) and the risk of the cardiovascular composite endpoint (total of 219 events) was significantly increased in those patients with reduced estimated glomerular filtration rate (GFR) [log rank (Mantel–Cox) 26.74, P < 0.001] as was the risk of death from any cause (total of 214 deaths) [Log Rank (Mantel–Cox) 56.97, P < 0.001]. On the basis of the proportional hazards model, while adjusting for other significant covariates, reduced estimated GFR was associated with a significant increase in risk of the primary and secondary outcomes (P < 0.01). For every 10 ml decrement in estimated GFR there was a corresponding 20% increase in hazard of the cardiovascular composite endpoint and a 33% increase in hazard of death from any cause. Conclusions. Estimated GFR appears to discriminate prognosis between patients with established cardiovascular disease. These results emphasise the importance of recognising chronic kidney disease as a significant risk factor in patients with cardiovascular disease in the community.

Stratification of women with screen-detected ductal carcinoma in situ (DCIS) by risk of subsequent invasive breast cancer (IBC) could assist treatment planning and selection of surveillance protocols that accord with risk. We assessed the utility of routinely collected administrative data for stratifying by IBC risk following DCIS detection in a population-based screening programme to inform ongoing surveillance protocols.A retrospective cohort design was used, employing linked data from the South Australian breast screening programme and cancer registry. Women entered the study at screening commencement and were followed until IBC diagnosis, death or end of the study period (1 December 2010), whichever came first. Routinely collected administrative data were analyzed to identify predictors of invasive breast cancer.Proportional hazards regression confirmed that the DCIS cohort had an elevated risk of IBC after adjustment for relevant confounders (HR = 4.0 (95% CL 3.4, 4.8)), which accorded with previous study results. Within the DCIS cohort, conservative breast surgery and earlier year of screening commencement were both predictive of an elevated invasive breast cancer risk.These linked cancer registry and administrative data gave plausible estimates of IBC risk following DCIS diagnosis, but were limited in coverage of key items for further risk stratification. It is important that the research utility of administrative datasets is maximized in their design phase in collaboration with researchers.

Metabolic syndrome is an increasingly common condition that can contribute to the development of type 2 diabetes and cardiovascular disease. 35 % of adults living in the United States meet the criteria for having metabolic syndrome, with that number being even higher in populations with health disparities. We describe a ‘healthy lifestyles’ program implemented at a free clinic serving a predominantly Hispanic cohort of low-income, uninsured individuals living in Providence, Rhode Island. The “Vida Sana/Healthy Life” (Vida Sana) program uses low literacy, language-appropriate materials and trained peers to educate participants about healthy lifestyles in a setting that also provided opportunities for social engagement. 192 of 126 (65.6 %) participants in Vida Sana completed 6 out of 8 sessions of the Vida Sana program over a 12-month period. At the completion of the program, nearly 90 % of Vida Sana participants showed an increase in their health literacy, and at least 60 % of participants decreased each of the risk factors (blood sugar, cholesterol, body mass index or waist circumference) associated with metabolic syndrome.

Opioid dose escalation may cause hyperalgesia, mediated by the N-methyl-D-aspartate (NMDA) pathway. Methadone is an atypical opioid that inhibits hyperalgesia through NMDA-blockade, especially at low doses.To evaluate the efficacy of using very-low-dose methadone as the sole long-acting opioid agent in a hospice practice.A retrospective, observational study of the use of methadone, ≤15 mg daily, with as-needed short-acting opiates. Adjuvant nonopioid medications included haloperidol, which may have NMDA-blocking effects.We reviewed the records of 240 patients admitted to a community-based hospice from July 1, 2011 to April 1, 2012, with data collected until hospice discharge or until April 30, 2012.Descriptive statistics were used to summarize patient demographics, medication regimens, and reported pain scores measured on a numeric rating scale from 0 to 10.All patients received short-acting opiates, in a morphine-equivalent dose of 5 mg every 4 hours as needed, while 40% also received methadone at a median daily dose of 5 mg. Of those on methadone, almost half received scheduled haloperidol. The population had a median reported pain score of 0 and a peak score of 3, with similar results seen for cancer and noncancer groups. Two-thirds of patients never reported a pain score greater than 3.The use of very-low-dose methadone in conjunction with adjuvant haloperidol resulted in excellent pain control without dose escalation or opioid-induced hyperalgesia, for both cancer and noncancer diseases. We conclude that low-dose methadone should be part of first-line treatment in palliative pain management.

Purpose : Patients with metastatic retinoblastoma have a poor outcome. Hope that early detection of extraocular spread will improve survival has led to routine monitoring with bone marrow and cerebrospinal fluid (CSF) examinations. In light of cost and patient morbidity, the clinical utility of this practice is questioned. Patients and Methods : We have performed 254 serial bone marrow aspirations and 164 lumbar punctures in 60 children with retinoblastoma. Results : Two patients with extensive intraocular disease at diagnosis developed positive bone marrow aspirations, although no patient died of distant metastasis. Three patients developed positive CSF examinations. All had neurologic symptoms at the time of CSF positivity. Conclusions : We recommend performing staging bone marrow and CSF evaluations only in patients with clinical, histologic, or radiologic evidence of local or systemic extension (Pratt stage III-IV), or in patients presenting with one Reese-Ellsworth group V eye and retrolaminar or extrascleral extension of their tumor. We recommend limiting follow-up bone marrow and CSF evaluations to patients who develop objective signs and symptoms of metastatic or regionally recurrent disease.

The effectiveness of antibiotic prophylaxis for prevention of surgical site infection (SSI) following specific types of breast cancer surgery remains uncertain. This study assessed the effectiveness of prophylaxis in modified radical mastectomy (MRM). Women undergoing MRM for breast cancer were recruited. Women were excluded who had diabetes mellitus, severe malnutrition or known allergy to cephalosporins; were receiving corticosteroid therapy or were treated with antibiotics within one week prior to surgery; were scheduled for simultaneous breast reconstruction or bilateral oophorectomy; had existing local infection. Participants were randomized to receive either intravenous cefazolin 1 g or placebo within 30 min prior to skin incision. Standard skin preparation and operative technique for MRM were carried out. Wounds were assessed for SSI and other complications weekly for 30 days. A total of 254 women were recruited. Age, clinical stage, prior chemotherapy, and operative time were similar for antibiotic and placebo groups. The overall incidence of SSI was 14.2 %. There were no significant differences in the infection rate over the 30-day follow-up period between the placebo and antibiotic groups (15 % vs 13.4 %; p = 0.719) or at each week. The majority of SSI were either cellulitis or superficial infection for both groups. There were no significant differences between groups in treatments required for SSI, incidence of hematoma or seroma. The findings of this study, alone and when meta-analyzed with data from studies in similar surgical populations, do not support the use of antibiotic prophylaxis in MRM.

Background Inguinal hernia is a common condition and its repair (herniorrhaphy) is one of the most commonly performed procedures in general surgery. The Lichtenstein herniorrhaphy technique is a widely used and effective surgery that uses mesh to reinforce the area of weakness. Although a wide range of mesh sizes are available for use in hernia repair, in low-resource health care settings the provision of multiple products may not be supportable and it may be necessary for the provision and use of a single mesh size. This study aimed to determine whether the recommended 7.0 cm x 15.0 cm size is an appropriate single mesh size. Methods In order to determine the optimal mesh size according to recommended surgical practices, in vivo measurements of key dimensions of the inguinal floor were taken in patients undergoing herniorrhaphy. Results Measurements were taken in 43 patients: 40 men and 3 women, mean age 43 years (SD 13.6); 39 with indirect hernias, 4 with direct. Allowing for recommended mesh overlaps, the optimal mesh size for provision to be appropriate for the majority of patients was determined to be 8.5 cm x 14.0 cm, 21% wider than the mesh size currently recommended for use in Lichtenstein herniorrhaphy. Conclusions An appropriate size for routine provision in low-resource settings, or other settings where the provision of several mesh sizes is not supportable, may be 8.5 cm x 14.0 cm.

BACKGROUND National policies are being developed, which may limit access to patients' records for health research. This could reduce the ability of health research to benefit society as a whole. It is important to develop an in-depth understanding of people's views across demographic groups to inform such policy development. Aims. To explore patients' views about the use of their general practice records in health research with attention to gender and age. Design of study. Qualitative study using focus groups. SETTING Six General Practices in the west of Ireland. METHOD Focus Group interviews with 35 people who were patients at the practices. RESULTS Overall, participants were positively inclined towards the idea of information from their records (anonymous and identifiable) being used in research for the 'greater good' although there were some concerns about personal information being 'leaked'. Males emphasized risks in relation to employment and finances, whereas females emphasized risks in relation to social discomfort and embarrassment. Participants were supportive of consent models that enable patients to give prior ongoing consent for specific agreed 'levels' of data use, affording patients self-determination without the need for consent request on study-by-study basis. CONCLUSION Overall male and female patients of different ages are supportive of the use of their general practice records in health research and of general practitioners as data protectors.

Aims To determine surgeons' views on invasive urodynamic testing (IUT) prior to surgery for stress (SUI) or stress predominant mixed urinary incontinence (MUI). Methods Members of British Society of Urogynaecology (BSUG) and British Association of Urological Surgeons Section of Female, Neurological and Urodynamic Urology (BAUS-SFNUU) were sent an email invitation to complete an online “SurveyMonkey®” questionnaire regarding their current use of IUT prior to surgical treatment of SUI, their view about the necessity for IUT in various clinical scenarios, and their willingness to randomize patients into a future trial of IUT. A purposive sample of respondents was invited for telephone interview to explore further how they use IUT to inform clinical decisions, and to contextualize questionnaire responses. Results There were 176/517 (34%) responses, 106/332 (32%) from gynecologists/urogynecologists and 67/185 (36%) from urologists; all respondents had access to IUT, and 89% currently arrange IUT for most women with SUI or stress predominant MUI. For a variety of scenarios with increasingly complex symptoms the level of individual equipoise (“undecided” about IUT) was very low (1–6%) and community equipoise was, at best, 66:34 (IUT “essential” vs. “unnecessary”) even for the simplest scenario. Nevertheless, 70% rated the research question underlying the proposed studies “very important” or “extremely important;” 60% recorded a “willingness to randomize” score ≥8/10. Conclusions Most urogynecologists and urologists consider IUT essential before surgery in SUI with or without other symptoms. Most however recognize the need for further research, and indicated a willingness to recruit into multicenter trials addressing this question. Neurourol. Urodynam. 31:?–?, 2012. © 2012 Wiley Periodicals, Inc.

Background: Following an AMI, it is important for patients and their physicians to appreciate the subsequent risk of death, and the potential benefits of invasive cardiac procedures and secondary preventive therapy. Studies, to-date, have focused largely on high-risk populations. We wished to determine the risk of death in a population-derived cohort of 2,887 patients after a first acute myocardial infarction (AMI). Methods: Logistic regression and survival analysis were conducted to investigate the effect of different baseline characteristics, pharmacological therapies and revascularization procedures on coronary heart disease (CHD) and all-cause mortality outcomes. Results: Within five years 44.4% of patients died (27.1% short-term [= 30 days]). Percutaneous transluminal coronary angioplasty (Adjusted Hazards Ratio (AHR) = 0.49, 95% Confidence Interval (CI) 0.26-0.93), beta-blockers (AHR = 0.58, 95% CI 0.46-0.74) and statins (AHR = 0.60, 95% CI 0.47-0.77) were all associated with significant reductions in longer-term CHD-related mortality. However, not all patients received secondary preventive therapy (8.7%). Diabetes (AHR = 1.83, 95% CI 1.43-2.34), stroke (AHR = 1.73, 95% CI 1.35-2.22), heart failure (AHR = 1.69, 95% CI 1.28-2.22), smoking (AHR = 1.72, 95% CI 1.18-2.51) and obesity (>30 kg/m(2); AHR = 1.39, 95% CI 1.01-1.90) increased the risk of longer-term mortality independent of other risk factors. Conclusions: It is encouraging that the coronary procedure PTCA and pharmacological secondary prevention therapies were found to be strongly associated with an important reduced risk of subsequent death, although not all patients received these interventions. Smoking, being obese and having cardiovascular related disease at baseline were also associated with an increased likelihood of longer-term mortality, independent of other baseline characteristics. Thus, the provision of smoking cessation, advice on diet (for obese patients) and optimal treatment is likely to be crucial for reducing mortality in all patients after AMI.

Background Hip fracture is a common problem in people aged > 60 years. The treatment options for individuals with high pre-fracture mobility, function and independence are hemiarthroplasty (HA) and total hip arthroplasty (THA). Objective The aim of this report is to assess the clinical effectiveness and cost-effectiveness evidence of THA compared with HA in patients with displaced intracapsular fracture who are cognitively intact with high pre-fracture mobility or function. Data sources A systematic search was made of 11 databases of published and unpublished literature from their inception to december 2010: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Biological Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science, UK Clinical Trials Research Network and the National Research Register archive, Current Controlled Trials and ClinicalTrials.gov. Review methods A systematic review of randomised controlled trials (RCTs) to assess the effectiveness of THA compared with HA in terms of dislocations, revisions, pain and function, and quality of life. Meta-analysis, independent subgroup analyses and exploratory cost-effectiveness modelling were performed. Results The literature search identified 532 unique citations, of which eight RCTs with almost 1000 participants satisfied the criteria for the effectiveness review. Meta-analysis found a statistically significant increased risk of dislocation for patients treated with THA compared with HA (p = 0.01), but a reduced risk of revision (p = 0.0003). There were no differences in terms of mortality. In all trials, individuals treated with THA reported better function and mobility and less pain than those treated with HA. Four trials reporting utility data found similar trends. Sensitivity analyses indicated that there were no statistically significant differences in outcomes based on follow-up, study quality, surgical approach taken, type of head or the use of cement. Four papers reported a cost-utility analysis or the cost-effectiveness of THA compared with HA. Exploratory modelling was undertaken that showed that THA is likely to be cost-effective compared with HA even when the limitations of the data and methodology are considered. Limitations The costs and disutilities associated with revisions and dislocations were not included in the economic evaluation. Conclusions THA appears to be more cost-effective than HA. It is likely that THA will be associated with increased costs in the initial 2-year period, but lower longer-term costs, owing to potentially lower revision rates. However, these longer-term costs have not been modelled. The capacity and experience of surgeons to perform THA have not been explored and these would need to be addressed at local level were THA to become recommended for active, elderly patients in whom THA is not contraindicated. Further studies examining the impact of surgeon experience on performing the two procedures may offer more robust evidence on outcomes. Funding The National Institute for Health Research Health Technology Assessment programme.

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010.

Obstructive uropathy is a recognized complication in advanced cervical cancer. Urinary diversion is commonly used to bypass the obstruction and improve renal function. The degree of survival benefit that diversion offers is not well established and its impact on quality of life (QoL) is uncertain. This study considered these factors in order to inform treatment decisions.This study examined a prospective cohort of patients with advanced cervical cancer and obstructive uropathy in Manila, Philippines. Age, cancer treatment status, comorbidities, serum creatinine level, degree of obstructive uropathy and QoL were recorded at baseline. Patients with creatinine values150 µmol/L, or who were being considered for radiotherapy or nephrotoxic chemotherapy or manifesting uncontrolled or recurrent uropathy-related urinary tract infection, were offered diversion. Follow-up data collection was at 3, 6, 9 and 12 months from cohort entry.Of the 230 patients invited, 205 patients joined the cohort. Complete data were available for 198, of whom 93 underwent diversion, 56 required diversion but elected not to receive it, and 49 did not require it. Although survival at 12 months among those who underwent diversion was no greater than among those who required but elected not to receive the procedure, diversion was associated with significantly improved chance of survival in the shorter term. There was no significant difference in the QoL between the groups throughout the study.With no evidence of an impact on QoL, the decision to offer diversionary surgery might be based solely on a survival benefit, which is modest but potentially important to patients.

Functional overlap of retinoblastoma protein stability and activity reveals a novel conserved regulatory pathway during Drosophila development., The Retinoblastoma (RB) transcriptional corepressor and related family of pocket proteins play central roles in cell cycle control and development, and the regulatory networks governed by these factors are frequently inactivated during tumorigenesis. During normal growth, these proteins are subject to tight control through at least two mechanisms. First, during cell cycle progression, repressor potential is down-regulated by Cdk-dependent phosphorylation, resulting in repressor dissociation from E2F family transcription factors. Second, RB proteins are subject to proteasome-mediated destruction during development. To better understand the mechanism for RB family protein instability, we characterized Rbf1 turnover in Drosophila and the protein motifs required for its destabilization. We show that specific point mutations in a conserved C-terminal instability element strongly stabilize Rbf1, but strikingly, these mutations also cripple repression activity. Rbf1 is destabilized specifically in actively proliferating tissues of the larva, indicating that controlled degradation of Rbf1 is linked to developmental signals. The positive linkage between Rbf1 activity and its destruction indicates that repressor function is governed in a manner similar to that described by the degron theory of transcriptional activation. Analogous mutations in the mammalian RB family member p107 similarly induce abnormal accumulation, indicating substantial conservation of this regulatory pathway.

Objectives To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. Data sources The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. Study selection The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI. Data extraction Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. Results Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions. Limitations Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies. Conclusions More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.

Background: It is unclear whether long-acting β-agonists with concomitant inhaled corticosteroids increase asthma-related intubations and deaths. We pooled data on long-acting β-agonists with variable and concomitant inhaled corticosteroids to evaluate the risk for catastrophic asthma events. Methods: We conducted searches of electronic databases, the US Food and Drug Administration website, clinical-trials registries, and selected references through December 2008. We analyzed randomized controlled trials in patients with asthma, which lasted at least 3 months, evaluated long-acting β-agonists compared with placebo or long-acting β-agonists with inhaled corticosteroids compared with corticosteroids alone, and included at least 1 catastrophic event, defined as asthma-related intubation or death. Results: In pooled trial data that included 36,588 participants, long-acting β-agonists increased catastrophic events 2-fold (Peto odds ratio [OR] 2.10; 95% confidence interval [CI], 1.37-3.22). Statistically significant increases were seen for long-acting β-agonists with variable corticosteroids compared with placebo (OR 1.83; 95% CI, 1.14-2.95) and for concomitant treatment with corticosteroids compared with corticosteroids alone (OR 3.65; 95% CI, 1.39-9.55). Similar increases in risk were seen for variable and concomitant corticosteroid use, salmeterol and formoterol, and children and adults. When the analysis was restricted to trials with controlled corticosteroid use, given as part of the study intervention, concomitant treatment still increased catastrophic events compared with corticosteroids alone (OR 8.19; 95% CI, 1.10-61.18). Conclusion: Long-acting β-agonists increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant inhaled corticosteroids.

Objective: Both prevalent and incident cohorts have been used in epidemiological and prognostic studies of ischemic heart disease (IHD). This study considers the differences between the cohort types. Study Design and Setting: Using linked primary care, secondary care, and death certification data, prevalent and incident cohorts of people with a first acute myocardial infarction (AMI) were formed from the same population. They were analyzed independently in terms of baseline characteristics and survival to revascularization, another AMI, or death. Results: 55.7% of the prevalent cohort members were males, with a mean age of 71.0 years (standard deviation [SD]: 12.0). 59.0% of the incident cohort members were males, with a mean age of 64.7 years (SD: 13.3). Over 5 years, a greater proportion of prevalent cases died from any cause (31.4% [95% confidence interval(CI): 28.6e34.3]) and IHD (18.5% [95% CI: 16.2e21.0]) than incident cases (18.0% [95% CI: 15.0e21.4] and 12.2% [95% CI: 9.7e15.2], respectively). Mean time to death was shorter in prevalent cases. There was a small difference in the numbers of subsequent AMIs between cohorts. In the incident cohort, mean time to AMI was shorter. Fewer prevalent cases underwent coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Conclusion: Considerable differences existed between the two cohorts in terms of baseline characteristics and prognosis. Incident cohorts derived from whole populations should be sought for estimation of survival. 2010 Elsevier Inc. All rights reserved.

Background: There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue. Methods: A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 month's duration that evaluated hormone therapy in women with mean age

Objectives To summarize existing evidence relating to the prevalence and risk factors of urinary incontinence in order to provide a concise reference source for clinicians, health researchers, and service planners. Methods For the Fourth International Consultation on Incontinence (4th ICI) world experts identified, collated, and reviewed the best available evidence. Estimates of prevalence from different studies are presented as ranges. Results Most studies report some degree of urinary incontinence (UI) in 25-45% of women; 7-37% of women aged 20-39 report some UI; “daily UI” is reported by 9% to 39% of women over 60. Pregnancy, childbirth, diabetes and increased body mass index are associated with an increased risk of UI. Prevalence of UI in men approximately half that in women: UI is seen in 11-34% of older men, with 2-11% reporting daily UI. Surgery for prostate disease is associated with an increased risk. Some 10% of children aged seven, 3% of 11-12 years olds and 1% of 16-17 year olds are not dry at night. Conclusions UI is clearly common, but accurate prevalence data have proven difficult to establish because of heterogeneity between studies in terms of methodologies, definitions of UI and populations considered. Future research should use standardized, validated and more readily comparable methods.

Aims Research often neglects important gaps in existing evidence. Throughout healthcare, clinicians and patients face avoidable “clinical uncertainties” daily, making decisions about treatments without reliable evidence about their effects. This partnership of patients and clinicians aimed to identify and prioritize “clinical uncertainties” relating to treatment of urinary incontinence (UI). Methods UK clinician and patient organizations whose remit includes UI were invited to participate. Participating organizations consulted memberships to identify “uncertainties” affecting treatment decisions. “Uncertainties” were also identified in published research recommendations. Prioritization involved two phases: shortlisting of “uncertainties” by organizations; patient-clinician prioritization using established consensus methods. Prioritized “uncertainties” were verified by checking any available relevant up-to-date published systematic reviews. Results Thirty organizations were invited; 8 patient and 13 clinician organizations participated. Consultation generated 417 perceived “uncertainties,” research recommendations 131. Refining, excluding and combining produced a list of 226. Prioritization shortlisted 29 “uncertainties,” then a “top ten” (5 submitted by clinicians, 4 by patients, 1 from research recommendations). Conclusions The partnership successfully developed and tested a systematic and transparent methodology for patient–clinician consultation and consensus. Through consensus, unanswered research questions of importance to patients and clinicians were identified and prioritized. The final list reflects the heterogeneity of populations, treatments and evidence needs associated with UI. Some prioritized “uncertainties” relate to treatments that are widely used yet whose effects are not thoroughly understood, some to access to care, some to precise surgical questions. Research needs to address the uncertainties range from systematic reviewing to primary research. Neurourol. Urodynam. 29:708–714, 2010. © 2010 Wiley-Liss, Inc.

OBJECTIVE: To ascertain the risk of acute myocardial infarction, invasive cardiac procedures, and mortality among patients with newly diagnosed angina over five years. DESIGN: Incident cohort study of patients with primary care data linked to secondary care and mortality data. SETTING: 40 primary care practices in Scotland. PARTICIPANTS: 1785 patients with a diagnosis of angina as their first manifestation of ischaemic heart disease, 1 January 1998 to 31 December 2001. MAIN OUTCOME MEASURES: Adjusted hazard ratios for acute myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, death from ischaemic heart disease, and all cause mortality, adjusted for demographics, lifestyle risk factors, and comorbidity at cohort entry. RESULTS: Mean age was 62.3 (SD 11.3). Male sex was associated with an increased risk of acute myocardial infarction (hazard ratio 2.01, 95% confidence interval 1.35 to 2.97), death from ischaemic heart disease (2.80, 1.73 to 4.53), and all cause mortality (1.82, 1.33 to 2.49). Increasing age was associated with acute myocardial infarction (1.04, 1.02 to 1.06, per year of age increase), death from ischaemic heart disease (1.09, 1.06 to 1.11, per year of age increase), and all cause mortality (1.09, 1.07 to 1.11, per year of age increase). Smoking was associated with subsequent acute myocardial infarction (1.94, 1.31 to 2.89), death from ischaemic heart disease (2.12, 1.32 to 3.39), and all cause mortality (2.11, 1.52 to 2.95). Obesity was associated with death from ischaemic heart disease (2.01, 1.17 to 3.45) and all cause mortality (2.20, 1.52 to 3.19). Previous stroke was associated with all cause mortality (1.78, 1.13 to 2.80) and chronic kidney disease with death from ischaemic heart disease (5.72, 1.74 to 18.79). Men were more likely than women to have coronary artery bypass grafting or percutaneous transluminal coronary angioplasty after a diagnosis of angina; older people were less likely to receive percutaneous transluminal coronary angioplasty. Acute myocardial infarction after a diagnosis of angina was associated with an increased risk of death from ischaemic heart disease and all cause mortality (8.84 (5.31 to 14.71) and 4.23 (2.78 to 6.43), respectively). Neither of the invasive cardiac procedures significantly reduced the subsequent risk of all cause mortality. CONCLUSIONS: In this sample of people with incident angina from primary care, there were sex differences in survival and age and sex differences in the provision of revascularisation after a diagnosis. Acute myocardial infarction after a diagnosis of angina was strongly predictive of mortality. To minimise adverse outcomes, optimal preventive treatments should be used in patients with angina.

Objective To provide evidence on outcomes of importance to women who have stress urinary incontinence (SUI). The secondary aim was to identify additional outcomes that ought to be collected in future primary studies or in systematic reviews of the literature. Design Questionnaire survey of a cohort of women with SUI. Setting UK. Sample A total of 188 women with SUI. Methods Areas of importance to women who suffer from SUI were assessed using a patient generated index (PGI). In addition to the PGI, the questionnaire included the King’s Health Questionnaire (KHQ) and the EuroQol-5D (EQ-5D). Main outcome measures PGI, EQ-5D and the KHQ. Results In total, 38 different areas were reported by respondents on the PGI. PGI and EQ-5D scores were positively correlated and significant. Correlations between the seven domains of the KHQ and PGI were all negative, but only two were statistically significant: personal relationships and severity measures. Conclusions The PGI succeeded in capturing a diverse range of outcomes of importance to women suffering with SUI. Given the limited correlation between the KHQ domains and the PGI and, in addition, that the areas mentioned in the PGI were not found to map well to the EQ-5D, the PGI in this instance may be capturing concerns of women who suffer from SUI, which are not captured by quality-of-life measures such as the EQ-5D.

Summary Aim: To determine relative prevalence in the same population of urinary incontinence (UI), faecal incontinence (FI) and nocturnal enuresis (NE). To explore attitudes and behaviours relating to help-seeking and beliefs about incontinence prevalence, impact, causes and treatments. Design: Online survey. Subjects: A total of 1040 community-based adults in the UK, representative in terms of age, gender, region and socio-economic status. Outcomes: Prevalence of UI, FI and NE; help-seeking behaviour and beliefs; beliefs about cause, impact and treatment of incontinence. Results: Twenty-three per cent (n = 239) reported UI, 11% (n = 110) FI and 6% (n = 57) NE. Of those known to have sought help, 77% did so from a general practitioner (GP). Of those with no incontinence, 75% said they would seek help from a GP, while 23% said they did not know who they would seek help from. Many were unsure whether treatments were available. Around 90% recognised the serious personal impact of incontinence. Conclusions: This survey suggests that, relative to UI, the prevalence of FI and NE may be higher than previous UK studies. That the majority of those who had sought help did so from a GP, and that those with no incontinence thought that they would do so if affected, underlines the importance of GP education in the diagnosis and management of incontinence and the need to raise public awareness of other sources of help. That many respondents were unsure of treatment options and yet aware of the impact of incontinence underlines the importance of awareness-raising.

Aim: To compare prognosis for patients with a diagnosis of angina alone to patients postacute myocardial infarction (AMI) and/or revascularisation and/or angina. Design: Community-based retrospective cohort study. Setting: A random selection of 37 Irish general practices. Participants: 1,609 adults with ischaemic heart disease (IHD) identified in 2000/1. Intervention: Medical records searches and postal questionnaires in 2000/1 and 2005/6. Outcome measures: Primary: all-cause and IHD-related mortality. Secondary: acute myocardial infarction (AMI), cardiac artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA); physical and mental health status as measured by SF36 and SF12; process of care measurements and behavioural risk factor outcomes. Results: Compared with patients with previous AMI and/or revascularisation, patients with angina alone had slightly lower risks of all-cause and IHD-related death: however, although hazard ratios of 0.73 (95% CI 0.55 to 0.98) and 0.65 (95% CI 0.44 to 0.98), respectively, were significant at the p < 0.05 level, they were not significant at the p < 0.01 level currently suggested as appropriate in observational research. Proportional hazards models identified no statistically significant differences in adjusted risks of subsequent AMI, CABG or PTCA between patients with angina-alone and those with other IHD. Over the 4.5-year follow-up, physical functioning was consistently lower among those with angina alone, and the extent to which physical functioning was increasingly impaired was slightly greater. Conclusions: Prognosis to death or cardiac outcomes for patients with angina alone was similar to those with previous AMI and/or revascularisation, while health status was poorer. The clinical importance of angina should not be underestimated in primary care. Further descriptive research is needed among representative community cohorts of people with angina.