Long-gap esophageal atresia: gastric transposition or esophageal lengthening with delayed primary anastomosis? A systematic review.

PURPOSE: This study aims to evaluate different surgical approaches to long-gap esophageal atresia (LGEA) with or without tracheoesophageal fistula (TEF) is unclear. METHODS: A systematic literature review was done comparing gastric transposition versus esophageal lengthening with delayed primary anastomosis in infants with LGEA+/-TEF. The primary outcome was time to full oral feeds. Secondary outcomes were time to full enteric feeds, need for further surgery, growth, mortality, and postoperative adverse events. RESULTS: No comparative studies were found. However, the literature was re-interrogated for non-comparative studies. Four hundred thirty-eight articles were identified and screened, and 18 met the inclusion criteria. All were case series. Forty-three infants underwent gastric transposition, and 106 had esophageal lengthening with delayed primary anastomosis. One study on gastric transposition reported time to full oral feeds, and one study in each group reported growth. Time to full enteric feeds was reported in one study in each group. 30% of infants had further surgery following gastric transposition, including hiatus hernia repair (5/43, 12%) and esophageal dilation (7/43, 16%). Following esophageal lengthening, 62/106 (58%) had anti-reflux surgery, 58/106 (55%) esophageal dilatation and 11/106 (10%) esophageal stricture resection. Anastomotic complications occurred in 13/43 (30%), gastrointestinal in 16/43 (37%), respiratory in 17/43 (40%), and nerve injury in 2/43 (5%) of the gastric transposition group. In the esophageal lengthening group, anastomotic complications occurred in 68/106 (64%), gastrointestinal in 62/106 (58%), respiratory in 6/106 (6%), and none sustained nerve injury. Each group had one death due to a cause not directly related to the surgical procedure. CONCLUSIONS: This systematic review highlights the morbidity associated with both surgical procedures and the variety in reporting outcomes.

Retinal and Choroidal Thickness in an Indigenous Population from Ghana: Comparison with Individuals with European or African Ancestry.

Purpose: To evaluate the thickness of the macular retina and central choroid in an indigenous population from Ghana, Africa and to compare them with those measured among individuals with European or African ancestry. Design: Cross-sectional study, systematic review, and meta-analyses. Participants: Forty-two healthy Ghanaians, 37 healthy individuals with European ancestry, and an additional 1427 healthy subjects with African ancestry from previously published studies. Methods: Macular retinal thickness in the fovea, parafovea, and perifovea and central choroidal thickness were extracted from OCT volume scans. Associations with ethnicity, age, and sex were assessed using mixed-effect regression models. Monte Carlo simulations were performed to determine the sensitivity of significant associations to additional potential confounders. Pooled estimates of retinal thickness among other groups with African ancestry were generated through systematic review and meta-analyses. Main Outcome Measures: Macular retinal thickness and central choroidal thickness and their association with ethnicity, age, and sex. Results: When adjusted for age and sex, the macular retina and central choroid of Ghanaians are significantly thinner as compared with subjects with European ancestry (P < 0.001). A reduction in retinal and choroidal thickness is observed with age, although this effect is independent of ethnicity. Meta-analyses indicate that retinal thickness among Ghanaians differs markedly from that of African Americans and other previously reported indigenous African populations. Conclusions: The thickness of the retina among Ghanaians differs not only from those measured among individuals with European ancestry, but also from those obtained from African Americans. Normative retinal and choroidal parameters determined among individuals with African or European ancestry may not be sufficient to describe indigenous African populations. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Study protocol for a randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: 2 (TOPIC 2).

BACKGROUND: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. METHODS: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. DISCUSSION: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. TRIAL REGISTRATION: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

Phase III, two arm, multi-centre, open label, parallel-group randomised designed clinical investigation of the use of a personalised early warning decision support system to predict and prevent acute exacerbations of chronic obstructive pulmonary disease: 'Predict & Prevent AECOPD' - study protocol.

INTRODUCTION: With 65 million cases globally, chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and imposes a heavy burden on patients' lives and healthcare resources worldwide. Around half of all patients with COPD have frequent (≥2 per year) acute exacerbations of COPD (AECOPD). Rapid readmissions are also common. Exacerbations impact significantly on COPD outcomes, causing significant lung function decline. Prompt exacerbation management optimises recovery and delays the time to the next acute episode. METHODS/ANALYSIS: The Predict & Prevent AECOPD trial is a phase III, two arm, multi-centre, open label, parallel-group individually randomised clinical trial investigating the use of a personalised early warning decision support system (COPDPredict) to predict and prevent AECOPD. We aim to recruit 384 participants and randomise each individual in a 1:1 ratio to either standard self-management plans with rescue medication (RM) (control arm) or COPDPredict with RM (intervention arm).The trial will inform the future standard of care regarding management of exacerbations in COPD patients. The main outcome measure is to provide further validation, as compared with usual care, for the clinical effectiveness of COPDPredict to help guide and support COPD patients and their respective clinical teams in identifying exacerbations early, with an aim to reduce the total number of AECOPD-induced hospital admissions in the 12 months following each patient's randomisation. ETHICS AND DISSEMINATION: This study protocol is reported in accordance with the guidance set out in the Standard Protocol Items: Recommendations for Interventional Trials statement. Predict & Prevent AECOPD has obtained ethical approval in England (19/LO/1939). On completion of the trial and publication of results a lay findings summary will be disseminated to trial participants. TRIAL REGISTRATION NUMBER: NCT04136418.

The frequency and nature of prescribing problems by GPs-in-training (REVISiT): a retrospective review.

BACKGROUND: Prescribing errors can cause significant morbidity and occur in about 5% of prescriptions in English general practices. AIM: To describe the frequency and nature of prescribing problems in a cohort of GPs-in-training to determine whether they need additional prescribing support. DESIGN & SETTING: A primary care pharmacist undertook a retrospective review of prescriptions issued between 9 October 2014 and 11 March 2015 by 10 GPs in their final year of training from 10 practices in England. METHOD: Pre-existing standards and expert panel discussion were used to classify the appropriateness of prescribing. Data were imported into Stata (version 13) to perform descriptive analysis. An individualised report highlighting prescribing errors, suboptimal prescribing, and areas of good practice identified during the review was shared with the GPs-in-training and their trainers. This report was used to guide discussions during the GP-in-training's feedback session. RESULTS: A total of 1028 prescription items were reviewed from 643 consultations performed by 10 GPs-in-training. There were 92 prescribing errors (8.9%) and 360 episodes of suboptimal prescribing (35.0%). The most common types of error concerned medication dosages (n = 30, 32.6% of errors). CONCLUSION: Personalised review of prescribing revealed an error rate higher than recorded in a previous similar study mainly comprising GPs who had completed postgraduate training, and a substantially higher rate of suboptimal prescribing. A larger intervention study is now required to evaluate the effectiveness of receiving a personalised review of prescribing, and to assess its impact on patient safety.

Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial.

Importance: In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness. Objective: To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. Design, Setting, and Participants: A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018. Interventions: Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474). Main Outcomes and Measures: Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. Results: Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). Conclusions and Relevance: In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02213380.

Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?

BACKGROUND/OBJECTIVE: Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed. METHODS: This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage. RESULTS: A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p = 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p = 0.010), 1.04 (CI = 0.22, 5.00; p = 0.956) and 0.98 (CI = 0.21, 4.58; p = 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p = 0.163). CONCLUSIONS: Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.

Incidence, nature and causes of avoidable significant harm in primary care in England: retrospective case note review.

OBJECTIVE: To estimate the incidence of avoidable significant harm in primary care in England; describe and classify the associated patient safety incidents and generate suggestions to mitigate risks of ameliorable factors contributing to the incidents. DESIGN: Retrospective case note review. Patients with significant health problems were identified and clinical judgements were made on avoidability and severity of harm. Factors contributing to avoidable harm were identified and recorded. SETTING: Primary care. PARTICIPANTS: Thirteen general practitioners (GPs) undertook a retrospective case note review of a sample of 14 407 primary care patients registered with 12 randomly selected general practices from three regions in England (total list size: 92 255 patients). MAIN OUTCOME MEASURES: The incidence of significant harm considered at least 'probably avoidable' and the nature of the safety incidents. RESULTS: The rate of significant harm considered at least probably avoidable was 35.6 (95% CI 23.3 to 48.0) per 100 000 patient-years (57.9, 95% CI 42.2 to 73.7, per 100 000 based on a sensitivity analysis). Overall, 74 cases of avoidable harm were detected, involving 72 patients. Three types of incident accounted for more than 90% of the problems: problems with diagnosis accounted for 45/74 (60.8%) primary incidents, followed by medication-related problems (n=19, 25.7%) and delayed referrals (n=8, 10.8%). In 59 (79.7%) cases, the significant harm could have been identified sooner (n=48) or prevented (n=11) if the GP had taken actions aligned with evidence-based guidelines. CONCLUSION: There is likely to be a substantial burden of avoidable significant harm attributable to primary care in England with diagnostic error accounting for most harms. Based on the contributory factors we found, improvements could be made through more effective implementation of existing information technology, enhanced team coordination and communication, and greater personal and informational continuity of care.

Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care.

OBJECTIVES: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care. METHODS: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat. RESULTS: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54). CONCLUSION: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications. TRIAL REGISTRATION NUMBER: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95).

'New Medicine Service': supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial.

OBJECTIVE: To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks. METHODS: Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective). RESULTS: Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: -£104 (95% CI -£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI -0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of -£113.9 (-1159.4, 683.7). The incremental cost-effectiveness ratio was -£2758/QALY (2.5% and 97.5%: -38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY. CONCLUSIONS: At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high. TRIAL REGISTRATION NUMBER: NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.

Identifying 'avoidable harm' in family practice: a RAND/UCLA Appropriateness Method consensus study.

BACKGROUND: Health care-related harm is an internationally recognized threat to public health. The United Kingdom's national health services demonstrate that upwards of 90% of health care encounters can be delivered in ambulatory settings. Other countries are transitioning to more family practice-based health care systems, and efforts to understand avoidable harm in these settings is needed. METHODS: We developed 100 scenarios reflecting a range of diseases and informed by the World Health Organization definition of 'significant harm'. Scenarios included different types of patient safety incidents occurring by commission and omission, demonstrated variation in timeliness of intervention, and conditions where evidence-based guidelines are available or absent. We conducted a two-round RAND / UCLA Appropriateness Method consensus study with a panel of family practitioners in England to define "avoidable harm" within family practice. Panelists rated their perceptions of avoidability for each scenario. We ran a k-means cluster analysis of avoidability ratings. RESULTS: Panelists reached consensus for 95 out of 100 scenarios. The panel agreed avoidable harm occurs when a patient safety incident could have been probably, or totally, avoided by the timely intervention of a health care professional in family practice (e.g. investigations, treatment) and / or an administrative process (e.g. referrals, alerts in electronic health records, procedures for following up results) in accordance with accepted evidence-based practice and clinical governance. Fifty-four scenarios were deemed avoidable, whilst 31 scenarios were rated unavoidable and reflected outcomes deemed inevitable regardless of family practice intervention. Scenarios with low avoidability ratings (1 s or 2 s) were not represented by the categories that were used to generate scenarios, whereas scenarios with high avoidability ratings (7 s 8 s or 9 s) were represented by these a priori categories. DISCUSSION: The findings from this RAND/UCLA Appropriateness Method study define the characteristics and conditions that can be used to standardize measurement of outcomes for primary care patient safety. CONCLUSION: We have developed a definition of avoidable harm that has potential for researchers and practitioners to apply across primary care settings, and bolster international efforts to design interventions to target avoidable patient safety incidents that cause the most significant harm to patients.

Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population-the Bridlington eye assessment project (BEAP): a cross-sectional study (2002-2006).

PURPOSE: There is paucity of data on the epidemiology of peripapillary choroidal neovascularisartion (PPCNV). Our aim was to determine prevalence of PPCNV in the elderly UK population of Bridlington residents aged ≥65 years. METHODS: Eyes with PPCNV in the Bridlington eye assessment project (BEAP) database of 3475 participants were analysed. PPCNV outline was drawn, its area measured, and clock-hour involvement of disc circumference recorded. Location and shortest distance from the lesion edge to fovea were recorded. Masked grading for age-related maculopathy (ARM)/reticular pseudodrusen (RPD) within the ETDRS grid was assigned for each eye using a modified Rotterdam scale. Peripapillary retinal pigment epithelial (RPE) changes/drusen were recorded. Visual acuity (VA) and demographic details analysed separately were merged with grading data. RESULTS: PPCNV were identified in ten subjects, and were bilateral in two (20%), a population prevalence of 0.29%, and 0.06% bilaterality. Gender-specific prevalence were 0.36% and 0.19% for females and males, respectively. Age ranged from 66 to 85 years [mean 76.3 (SD 6.4)]. PPCNV were located nasal to disc in 41.7%, measuring 0.46-7.93 mm2 [mean 2.81 mm2 (SD 2.82)]. All PPCNV eyes had peripapillary RPE changes. One subject had no ARM, 1 angioid streaks, and 30% RPD. No direct foveal involvement, or reduced VA attributable to PPCNV was observed. CONCLUSION: PPCNV were infrequent in this population, more common in females, and often located nasal to the disc, without foveal extension. Peripapillary degenerative changes were universal, and strong association with ARM was observed in eyes with PPCNV. Typically, PPCNV were asymptomatic with VA preservation.

Prevalence of reticular pseudodrusen in an elderly UK Caucasian population-The Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002-2006).

AIMS: To determine prevalence, associations, and risk factors for reticular pseudodrusen (RPD) in a UK population. METHODS: Cross-sectional study of Bridlington residents aged ≥65 years. Masked grading of colour fundus photographs from 3549 participants. RPD presence, phenotype, and topography were recorded, demographic details were analysed, and prevalence was calculated. RESULTS: RPD was detected in 281 eyes (176 individuals) of 3476 participants (5.06%) with gradable images, and bilateral in 76.6%. Digital enhancement increased detection by 15.7%. Prevalence increased significantly with age from 1.18% (65-69 years) to 27.27% (≥90 years) (mean age 81.1, SD 6.01; OR 1.18, 95% CI 1.15-1.21, p value <0.001), was higher in females (5.9% vs 4.0%; OR 1.52, 95% CI 1.09-2.13, p = 0.014), and associated with diabetes (OR 1.97, CI 1.20-3.17, p = 0.005). History of antihypertension treatment appeared protective (OR 0.64, 95% CI 0.46-0.90, p = 0.009). RPD subtypes were dot in 18.5%, ribbon in 36.7%, and mixed in 36.3%. RPD were located outside the ETDRS grid in 88%, and most commonly in the outer superior subfield. Central grid involvement occurred in 12.1% of right and 14.3% of left eyes. RPD occurred in 25.9% of participants with grade 4 AMD in at least one eye. RPD was associated with visual dissatisfaction after controlling for age (OR 0.63, 95% CI 0.45-0.88, p = 0.007). CONCLUSION: RPD occur more commonly than previously reported, most frequently in the upper-outer macular subfield, but also within the central subfield, albeit with reduced frequency and altered morphology. RPD may be associated with visual dissatisfaction and diabetes, but are less frequent in persons receiving antihypertension therapy.

Interpreting the Tinnitus Questionnaire (German version): what individual differences are clinically important?

OBJECTIVE: Reporting of clinical significance is recommended because findings can be statistically significant without being relevant to patients. For aiding clinical interpretation of the Tinnitus Questionnaire (TQ), many investigators use a 5-point change cut-off as a minimal clinically important difference (MCID). But there are shortcomings in how this value was originally determined. DESIGN: The MCID was evaluated by analysing retrospective clinical data on the TQ (German version). Following recommended standards, multiple estimates were computed using anchor- and distribution-based statistical methods. These took into account not only patients' experience of clinical improvement, but also measurement reliability. STUDY SAMPLE: Pre- and post-intervention scores were assessed for 202 patients. RESULTS: Our six estimates ranged from 5 to 21 points in TQ change score from pre- to post- intervention. The 5-point TQ change score was obtained using a method that considered change between groups, and did not account for measurement error or bias. The size of the measurement error was considerable, and this comprises interpretation of individual patient change scores. CONCLUSIONS: To enhance confidence that a TQ change over time in individual patients is clinically meaningful, we advise at least the median MCID of 12 points.

Author Response to Sabour (2018), "Comment on Hall et al. (2017), 'How to Choose Between Measures of Tinnitus Loudness for Clinical Research? A Report on the Reliability and Validity of an Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial'".

PURPOSE: The authors respond to a letter to the editor (Sabour, 2018) concerning the interpretation of validity in the context of evaluating treatment-related change in tinnitus loudness over time. METHOD: The authors refer to several landmark methodological publications and an international standard concerning the validity of patient-reported outcome measurement instruments. RESULTS: The tinnitus loudness rating performed better against our reported acceptability criteria for (face and convergent) validity than did the tinnitus loudness matching test. CONCLUSION: It is important to distinguish between tests that evaluate the validity of measuring treatment-related change over time and tests that quantify the accuracy of diagnosing tinnitus as a case and non-case.

Assessing the impact of the introduction of an electronic hospital discharge system on the completeness and timeliness of discharge communication: a before and after study.

BACKGROUND: Hospital discharge summaries are a key communication tool ensuring continuity of care between primary and secondary care. Incomplete or untimely communication of information increases risk of hospital readmission and associated complications. The aim of this study was to evaluate whether the introduction of a new electronic discharge system (NewEDS) was associated with improvements in the completeness and timeliness of discharge information, in Nottingham University Hospitals NHS Trust, England. METHODS: A before and after longitudinal study design was used. Data were collected using the gold standard auditing tool from the Royal College of Physicians (RCP). This tool contains a checklist of 57 items grouped into seven categories, 28 of which are classified as mandatory by RCP. Percentage completeness (out of the 28 mandatory items) was considered to be the primary outcome measure. Data from 773 patients discharged directly from the acute medical unit over eight-week long time periods (four before and four after the change to the NewEDS) from August 2010 to May 2012 were extracted and evaluated. Results were summarised by effect size on completeness before and after changeover to NewEDS respectively. The primary outcome variable was represented with percentage of completeness score and a non-parametric technique was used to compare pre-NewEDS and post-NewEDS scores. RESULTS: The changeover to the NewEDS resulted in an increased completeness of discharge summaries from 60.7% to 75.0% (p < 0.001) and the proportion of summaries created under 24 h from discharge increased significantly from 78.0% to 93.0% (p < 0.001). Furthermore, five of the seven grouped checklist categories also showed significant improvements in levels of completeness (p < 0.001), although there were reduced levels of completeness for three items (p < 0.001). CONCLUSION: The introduction of a NewEDS was associated with a significant improvement in the completeness and timeliness of hospital discharge communication.

Cost Effectiveness of Support for People Starting a New Medication for a Long-Term Condition Through Community Pharmacies: An Economic Evaluation of the New Medicine Service (NMS) Compared with Normal Practice.

BACKGROUND: The English community pharmacy New Medicine Service (NMS) significantly increases patient adherence to medicines, compared with normal practice. We examined the cost effectiveness of NMS compared with normal practice by combining adherence improvement and intervention costs with the effect of increased adherence on patient outcomes and healthcare costs. METHODS: We developed Markov models for diseases targeted by the NMS (hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma and antiplatelet regimens) to assess the impact of patients' non-adherence. Clinical event probability, treatment pathway, resource use and costs were extracted from literature and costing tariffs. Incremental costs and outcomes associated with each disease were incorporated additively into a composite probabilistic model and combined with adherence rates and intervention costs from the trial. Costs per extra quality-adjusted life-year (QALY) were calculated from the perspective of NHS England, using a lifetime horizon. RESULTS: NMS generated a mean of 0.05 (95% CI 0.00-0.13) more QALYs per patient, at a mean reduced cost of -£144 (95% CI -769 to 73). The NMS dominates normal practice with a probability of 0.78 [incremental cost-effectiveness ratio (ICER) -£3166 per QALY]. NMS has a 96.7% probability of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY. Sensitivity analysis demonstrated that targeting each disease with NMS has a probability over 0.90 of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY. CONCLUSIONS: Our study suggests that the NMS increased patient medicine adherence compared with normal practice, which translated into increased health gain at reduced overall cost. TRIAL REGISTRATION: ClinicalTrials.gov Trial reference number NCT01635361 ( http://clinicaltrials.gov/ct2/show/NCT01635361 ). Current Controlled trials: Trial reference number ISRCTN 23560818 ( http://www.controlled-trials.com/ISRCTN23560818/ ; DOI 10.1186/ISRCTN23560818 ). UK Clinical Research Network (UKCRN) study 12494 ( http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12494 ). FUNDING: Department of Health Policy Research Programme.

How to Choose Between Measures of Tinnitus Loudness for Clinical Research? A Report on the Reliability and Validity of an Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial.

PURPOSE: Loudness is a major auditory dimension of tinnitus and is used to diagnose severity, counsel patients, or as a measure of clinical efficacy in audiological research. There is no standard test for tinnitus loudness, but matching and rating methods are popular. This article provides important new knowledge about the reliability and validity of an audiologist-administered tinnitus loudness matching test and a patient-reported tinnitus loudness rating. METHOD: Retrospective analysis of loudness data for 91 participants with stable subjective tinnitus enrolled in a randomized controlled trial of a novel drug for tinnitus. There were two baseline assessments (screening, Day 1) and a posttreatment assessment (Day 28). RESULTS: About 66%-70% of the variability from screening to Day 1 was attributable to the true score. But measurement error, indicated by the smallest detectable change, was high for both tinnitus loudness matching (20 dB) and tinnitus loudness rating (3.5 units). Only loudness rating captured a sensation that was meaningful to people who lived with the experience of tinnitus. CONCLUSIONS: The tinnitus loudness rating performed better against acceptability criteria for reliability and validity than did the tinnitus loudness matching test administered by an audiologist. But the rating question is still limited because it is a single-item instrument and is probably able to detect only large changes (at least 3.5 points).

Understanding the epidemiology of avoidable significant harm in primary care: protocol for a retrospective cross-sectional study.

INTRODUCTION: Most patient safety research has focused on specialist-care settings where there is an appreciation of the frequency and causes of medical errors, and the resulting burden of adverse events. There have, however, been few large-scale robust studies that have investigated the extent and severity of avoidable harm in primary care. To address this, we will conduct a 12-month retrospective cross-sectional study involving case note review of primary care patients. METHODS AND ANALYSIS: We will conduct electronic searches of general practice (GP) clinical computer systems to identify patients with avoidable significant harm. Up to 16 general practices from 3 areas of England (East Midlands, London and the North West) will be recruited based on practice size, to obtain a sample of around 100 000 patients. Our investigations will include an 'enhanced sample' of patients with the highest risk of avoidable significant harm. We will estimate the incidence of avoidable significant harm and express this as 'per 100 000 patients per year'. Univariate and multivariate analysis will be conducted to identify the factors associated with avoidable significant harm. ETHICS/DISSEMINATION: The decision regarding participation by general practices in the study is entirely voluntary; the consent to participate may be withdrawn at any time. We will not seek individual patient consent for the retrospective case note review, but if patients respond to publicity about the project and say they do not wish their records to be included, we will follow these instructions. We will produce a report for the Department of Health's Policy Research Programme and several high-quality peer-reviewed publications in scientific journals. The study has been granted a favourable opinion by the East Midlands Nottingham 2 Research Ethics Committee (reference 15/EM/0411) and Confidentiality Advisory Group approval for access to medical records without consent under section 251 of the NHS Act 2006 (reference 15/CAG/0182).

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.