Evaluation of the association of area-level socioeconomic deprivation and breast cancer recurrence by oestrogen receptor subtypes in Scotland.

BACKGROUND: Women from socioeconomically deprived areas have lower breast cancer (BC) incidence rates for screen-detected oestrogen receptor (ER) + tumours and higher mortality for select tumour subtypes. We aimed to determine if ipsilateral breast cancer recurrence (IBR) differs by Scottish Index of Multiple Deprivation (SIMD) quintile and tumour subtype in Scotland. METHODS: Patient data for primary invasive BC diagnosed in 2007-2008 in Scotland was analysed. Manual case-note review for 3495 patients from 10 years post-diagnosis was used. To determine the probability of IBR while accounting for the competing risk of death from any cause, cumulative incidence functions stratified by ER subtype and surgery were plotted. Multivariable Cox Proportional Hazards models were used to estimate the association of SIMD accounting for other predictors of IBR. RESULTS: Among 2819 ER + tumours, 423 patients had a recurrence and 438 died. SIMD was related to death (p = 0.018) with the most deprived more likely to have died in the 10-year period (17.7% vs. 12.9%). We found no significant differences by SIMD in prognostic tumour characteristics (grade, TNM stage, treatment, screen-detection) or risk of IBR. Among 676 patients diagnosed with ER- tumours, 105 died and 185 had a recurrence. We found no significant differences in prognostic tumour characteristics by SIMD except screen detection with the most deprived more likely than the least to have their tumours detected from screening (46.9% vs. 28%, p = 0.03). Among patients with ER- tumours, 50% had mastectomy and the most deprived had increased 5-year IBR risk compared to the least deprived (HR 3.03 [1.41-6.53]). CONCLUSIONS: IBR is not a major contributor to mortality differences by SIMD for the majority of BC patients in our study. The lack of inequities in IBR are likely due to standardised treatment protocols and access to healthcare. The association with socioeconomic deprivation and recurrence for ER- tumours requires further study.

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer.

BACKGROUND: Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy. METHODS: We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed. RESULTS: A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups. CONCLUSIONS: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).

Interventions for perceptual disorders following stroke.

BACKGROUND: Perception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair perception in up to 70% of stroke survivors, leading to distress, increased dependence on others, and poorer quality of life. Interventions to address perceptual disorders may include assessment and screening, rehabilitation, non-invasive brain stimulation, pharmacological and surgical approaches. OBJECTIVES: To assess the effectiveness of interventions aimed at perceptual disorders after stroke compared to no intervention or control (placebo, standard care, attention control), on measures of performance in activities of daily living.  SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group, CENTRAL, MEDLINE, Embase, and three other databases to August 2021. We also searched trials and research registers, reference lists of studies, handsearched journals, and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adult stroke survivors with perceptual disorders. We defined perception as the specific mental functions of recognising and interpreting sensory stimuli and included hearing, taste, touch, smell, somatosensation, and vision. Our definition of perception excluded visual field deficits, neglect/inattention, and pain. DATA COLLECTION AND ANALYSIS: One review author assessed titles, with two review authors independently screening abstracts and full-text articles for eligibility. One review author extracted, appraised, and entered data, which were checked by a second author. We assessed risk of bias (ROB) using the ROB-1 tool, and quality of evidence using GRADE.  A stakeholder group, comprising stroke survivors, carers, and healthcare professionals, was involved in this review update. MAIN RESULTS: We identified 18 eligible RCTs involving 541 participants. The trials addressed touch (three trials, 70 participants), somatosensory (seven trials, 196 participants) and visual perception disorders (seven trials, 225 participants), with one (50 participants) exploring mixed touch-somatosensory disorders. None addressed stroke-related hearing, taste, or smell perception disorders. All but one examined the effectiveness of rehabilitation interventions; the exception evaluated non-invasive brain stimulation. For our main comparison of active intervention versus no treatment or control, one trial reported our primary outcome of performance in activities of daily living (ADL):  Somatosensory disorders: one trial (24 participants) compared an intervention with a control intervention and reported an ADL measure.  Touch perception disorder: no trials measuring ADL compared an intervention with no treatment or with a control intervention.  Visual perception disorders: no trials measuring ADL compared an intervention with no treatment or control.  In addition, six trials reported ADL outcomes in a comparison of active intervention versus active intervention, relating to somatosensation (three trials), touch (one trial) and vision (two trials).   AUTHORS' CONCLUSIONS: Following a detailed, systematic search, we identified limited RCT evidence of the effectiveness of interventions for perceptual disorders following stroke. There is insufficient evidence to support or refute the suggestion that perceptual interventions are effective. More high-quality trials of interventions for perceptual disorders in stroke are needed. They should recruit sufficient participant numbers, include a 'usual care' comparison, and measure longer-term functional outcomes, at time points beyond the initial intervention period. People with impaired perception following a stroke should continue to receive neurorehabilitation according to clinical guidelines.

Breast cancer incidence and survival in Scotland by socio-economic deprivation and tumour subtype.

BACKGROUND: Women from socio-economically deprived areas are less likely to develop and then to survive breast cancer (BC). Whether associations between deprivation and BC incidence and survival differ by tumour molecular subtypes and mode of detection in Scotland are unknown. METHODS: Data consisted of 62,378 women diagnosed with invasive BC between 2000 and 2016 in Scotland. Incidence rates and time trends were calculated for oestrogen receptor positive (ER+) and negative (ER-) tumours and stratified by the Scottish Index of Multiple Deprivation (SIMD) quintiles and screening status. SIMD is an area-based measure derived across seven domains: income, employment, education, health, access to services, crime and housing. We calculated adjusted hazard ratios (aHR [95% confidence intervals]) for BC death by immunohistochemical surrogates of molecular subtypes for the most versus the least deprived quintile. We adjusted for mode of detection and other confounders. RESULTS: In Scotland, screen-detected ER+tumour incidence increased over time, particularly in the least deprived quintile [Average Annual Percentage Change (AAPC) = 2.9% with 95% CI from 1.2 to 4.7]. No marked differences were observed for non-screen-detected ER+tumours or ER- tumours by deprivation. BC mortality was higher in the most compared to the least deprived quintile irrespective of ER status (aHR = 1.29 [1.18, 1.41] for ER+ and 1.27 [1.09, 1.47] for ER- tumours). However, deprivation was associated with significantly higher mortality for luminal A and HER2-enriched tumours (aHR = 1.46 [1.13, 1.88] and 2.10 [1.23, 3.59] respectively) but weaker associations for luminal B and TNBC tumours that were not statistically significant. CONCLUSIONS: Deprivation is associated with differential BC incidence trends for screen-detected ER+tumours and with higher mortality for select tumour subtypes. Future efforts should evaluate factors that might be associated with reduced survival in deprived populations and monitor progress stratified by tumour subtypes and mode of detection.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BACKGROUND: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. PATIENTS AND METHODS: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. RESULTS: In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (ρ = -0.51), warm detection (ρ = -0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). CONCLUSIONS: The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis.

BACKGROUND: Stroke rehabilitation interventions are routinely personalized to address individuals' needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. AIM: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. METHODS: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild-moderate/ moderate-severe based on language outcomes' median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. RESULTS: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants' greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3-4 SLT-h/week; ⩾ 50 hours). For moderate-severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild-moderate participants' greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males' greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. CONCLUSIONS: We observed a treatment response in most subgroups' overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild-moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate-severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.

Objective and Subjective Prevalence of Obstructive Sleep Apnoea/Hypopnoea Syndrome in UK Adults with Down Syndrome: A Strong Marker for Diurnal Behavioural Disturbances.

Prior to this study, the prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) in adults with Down syndrome was unknown. We hypothesized that unrecognised OSAHS could have an additional deleterious impact on mood and behavioural disturbances in this group of people. AIMS: To assess the prevalence of OSAHS in adults with Down syndrome in the United Kingdom, subjectively and objectively, and ascertain its association with diurnal behavioural disturbances. METHOD: Cross-sectional questionnaire study with home sleep apnoea testing (HSAT) during 2011-2015 across the four nations of the United Kingdom. Participants were adults aged ≥16 years with Down syndrome. Main outcome measures were: self- or caregiver-completed questionnaire data, including the Pictorial Epworth Sleepiness Scale (pESS), selected domains of the Developmental Behavioural Checklist for Adults (DBC-A), anthropometric measures, and symptoms of OSAHS. Objective prevalence was undertaken in a sample of responders using HSAT. RESULTS: Responses were received from 1321/5270 participants (25%), with 1105 valid responses (21%). Eighty-one participants (7%) reported a prior diagnosis of OSA, of whom 38 were receiving therapy. Using validated algorithms, a diagnosis of OSAHS was probable in 366 participants (35%), who were younger, with higher BMI and higher mean total pESS (p < 0.0001). A total of 23% of participants had a pESS > 10. OSAHS was a strong marker for behavioural disturbances on the DBC-A depression, disruption and anti-social subscales (p < 0.001). Of 149 individuals who underwent HSAT, 42% were diagnosed with OSAHS. CONCLUSIONS: Untreated OSAHS in Down syndrome is common and associated with behavioural and mood disturbances. Improving awareness of OSAHS amongst adults with Down syndrome, their families and healthcare professionals is essential.

Prospective Trial of CPAP in Community-Dwelling Adults with Down Syndrome and Obstructive Sleep Apnea Syndrome.

Adults with Down syndrome (DS) are predisposed to obstructive sleep apnoea (OSA), but the effectiveness and acceptability of continuous positive airway pressure treatment (CPAP) in this group has rarely been formally assessed. This study was designed as a pilot randomised, parallel controlled trial for one month, continuing as an uncontrolled cohort study whereby the control group also received the intervention. Symptomatic, community-dwelling DS individuals exhibiting ≥10 apnoeas/hypopneas per hour in bed on a Type 3 home sleep study were invited to participate in this study, with follow-up at 1, 3, 6, and 12 months from baseline. Measurements of sleepiness, behaviour, cognitive function and general health were undertaken; the primary outcome was a change in the pictorial Epworth Sleepiness Scale (pESS) score. Twenty-eight participants (19 male) were enrolled: age 28 ± 9 year; body mass index 31.5 ± 7.9 kg/m2; 39.6 ± 32.2 apnoeas/hypopneas per hour in bed; pESS 11 ± 6/24. The pilot randomised controlled trial at one month demonstrated no change between the groups. At 12 months, participant (p = 0.001) pESS and Disruptive (p < 0.0001), Anxiety/Antisocial (p = 0.024), and Depressive (p = 0.008) behaviour scores were reduced compared to baseline. Improvement was noted in verbal (p = 0.001) and nonverbal intelligence scores (p = 0.011). General health scores also improved (p = 0.02). At the end of the trial, 19 participants continued on treatment. Use of CPAP in adults with DS and OSA led to a number of significant, sustained improvements in sleepiness and behavioural/emotional outcomes at 12 months.

Mortality and morbidity in obstructive sleep apnoea-hypopnoea syndrome: results from a 30-year prospective cohort study.

BACKGROUND: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) carries substantial negative health consequences. This study examines factors affecting mortality and morbidity according to continuous positive airway pressure (CPAP) use and predictors affecting CPAP adherence in a longitudinal cohort of OSAHS patients. MATERIALS AND METHODS: This prospective, cohort study comprised 4502 patients who were diagnosed with OSAHS at a tertiary sleep disorders centre between 1982 and 2003. Of these, 1174 patients completed follow-up in 2012. Data collected included anthropometric, sleep and demographic characteristics, including comorbidities, ongoing medications and CPAP adherence. Patients were followed up for an average of 14.8±3.7 years. RESULTS: Imputation analysis showed that long-term CPAP users (>5 years) were 5.63 times more likely to be alive at study end than non-CPAP users (95% CI: 4.83-6.58, p<0.001) and 1.74-times more likely than short-term CPAP users (≤5 years) (95% CI: 1.49-2.02, p<0.001). Females had a significantly higher mortality rate during the follow-up period (26.8% versus 19.6%, p<0.001). Respiratory mortality was more common in patients with OSAHS, in particular those who did not use CPAP, compared to the general population (17.2% versus 12.2%, p=0.002 respectively), whereas deaths from cancer were less common compared to the general population (16.2% versus 25.6%, p<0.001). Compared to CPAP users, non-CPAP-users had a significantly increased incidence of type II diabetes mellitus (DMII) (27.9% versus 18.7%, p=0.003), ischaemic heart disease (IHD) (25.5% versus 12.7%, p<0.001) and myocardial infarction (MI) (14.7% versus 4.2%, p<0.001) at long-term follow-up. CONCLUSIONS: Long-term CPAP use in men and women with OSAHS reduces mortality and decreases the incidence of DMII and cardiovascular disease.

An analysis of clinical predictive values for radiographic pneumonia in children.

INTRODUCTION: Healthcare providers in resource-limited settings rely on the presence of tachypnoea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0-59 months of age. METHODS: We conducted an analysis using patient-level pooled data from 41 shared datasets of paediatric pneumonia. We included hospital-based studies in which >80% of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was used as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0-59 months of age. RESULTS: Ten studies met inclusion criteria comprising 15 029 children; 24.9% (n=3743) had radiographic pneumonia. The presence of age-based tachypnoea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation <90% was 0.40 and 0.67, respectively, and was 0.17 and 0.88 for oxygen saturation <85%. Specificity was improved when individual clinical factors such as tachypnoea, fever and hypoxaemia were combined, however, the sensitivity was lower. CONCLUSIONS: No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining individual signs and symptoms.

Early Postoperative Death in Patients Undergoing Emergency High-Risk Surgery: Towards a Better Understanding of Patients for Whom Surgery May Not Be Beneficial.

The timing, causes, and quality of care for patients who die after emergency laparotomy have not been extensively reported. A large database of 13,953 patients undergoing emergency laparotomy, between July 2014 and March 2017, from 28 hospitals in England was studied. Anonymized data was extracted on day of death, patient demographics, operative details, compliance with standards of care, and 30-day and in-patient mortality. Thirty-day mortality was 8.9%, and overall inpatient mortality was 9.8%. Almost 40% of postoperative deaths occurred within three days of surgery, and 70% of these early deaths occurred on the day of surgery or the first postoperative day. Such early deaths could be considered nonbeneficial surgery. Patients who died within three days of surgery had a significantly higher preoperative lactate, American Society of Anesthesiologists Physical Status (ASA-PS) grade, and Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM). Compliance with perioperative standards of care based on the Emergency Laparotomy Collaborative care bundle was high overall and better for those patients who died within three days of surgery. Multidisciplinary team involvement from intensive care, care of the elderly physicians, and palliative care may help both the communication and the burden of responsibility in deciding on the risk-benefit of operative versus nonoperative approaches to care.

Correction: A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1).

[This corrects the article DOI: 10.1371/journal.pone.0227695.].

A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1).

BACKGROUND: Endometriosis is defined by the presence of endometrial-like tissue (lesions) outside the uterus, commonly on the pelvic peritoneum. It affects 6-10% of women and is associated with debilitating pelvic pain. Current management options are often unsatisfactory. Omega-3 polyunsaturated fatty acids (O-PUFA) have the potential to reduce the painful symptoms associated with endometriosis, reduce lesion size, preserve the patient's ability to conceive, and have minimal side effects. We performed a two-arm, parallel double-blinded randomised controlled trial to inform the planning of a future multicentre randomised controlled trial to evaluate the efficacy of O-PUFA for endometriosis-associated pain. OBJECTIVES: The primary objectives of the trial were to assess recruitment and retention rates. The secondary objectives were to determine the acceptability to women of the proposed methods of recruitment, randomisation, treatments and questionnaires, to estimate the variability in the proposed primary endpoints to inform the sample size calculation and to refine the research methodology for the future definitive trial. METHODS: We recruited women with endometriosis from June 2016 to June 2017 and randomised them to eight weeks of treatment with O-PUFA or olive oil. Pain scores and quality of life questionnaires were collected at baseline and eight weeks. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to eight weeks. Acceptability questionnaires were used to evaluate women's experiences of the trial. RESULTS: The proportion of eligible participants who were randomised was 45.2% (33/73) and 81.8% (27/33) completed the study. The majority of participants described their overall trial experience favourably and there were no adverse events in either group. CONCLUSION: Our pilot trial supports the feasibility of a future larger trial to definitively evaluate the efficacy of O-PUFA for endometriosis-associated pain. TRIAL REGISTRATION: The trial was registered on the ISRCTN registry (registration number ISRCTN44202346).

RELEASE: a protocol for a systematic review based, individual participant data, meta- and network meta-analysis, of complex speech-language therapy interventions for stroke-related aphasia.

Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis. Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke. Methods and procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions. Outcomes and results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains. Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke. Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947).

Five-year oncological outcomes after selective neoadjuvant radiotherapy for resectable rectal cancer.

Introduction: There is considerable variation in selection of patients for and type of neoadjuvant radiotherapy administered in the treatment of resectable rectal cancer. The aim of this study was to report outcomes for patients with resected rectal cancer from a unit with step-wise selection for surgery alone, short course radiotherapy (SCRT) or downstaging long course chemoradiotherapy (LCCRT). Material and methods: Cohort analysis of patients with rectal adenocarcinoma resected with curative intent between 2008 and 2012 at a specialist regional colorectal surgery center. The primary endpoints were local recurrence, metastatic recurrence, disease-free survival and overall survival. Exploratory uni- and multi-variable regression analyses were performed to identify predictive factors. Results: About 240 patients were treated by surgery alone, 90 patients received SCRT and 91 patients received LCCRT. Five-year local recurrence was 10.8% in the surgery alone group, 3.3% with SCRT and 18.7% with LCCRT. Metachronous distant metastasis was highest in the SCRT group (13.8% surgery alone, 25.6% SCRT, 15.4% LCCRT). Uni- and multi-variable regression analysis found that local and distant recurrence was attributable predominantly to adverse tumor biology. Conclusions: Patients selected for SCRT had a lower rate of local recurrence than patients selected for surgery alone, but were more likely to develop distant metastasis. There was no difference in overall survival. With low local recurrence rates, distant metastasis is the predominant risk for patients with resectable rectal cancer.

The impact of meridian balance method electro-acupuncture treatment on chronic pelvic pain in women: a three-armed randomised controlled feasibility study using a mixed-methods approach.

INTRODUCTION: Chronic pelvic pain (CPP) is estimated to affect 6%-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP and it has been highlighted as a key area of unmet need. Standard treatments are associated with unacceptable side effects. The meridian balance method electro-acupuncture (BMEA), and traditional Chinese medicine health consultation (TCM HC) (BMEA + TCM HC = BMEA treatment) may be an effective adjunct to standard treatment. AIM: The aim of our study was to evaluate the feasibility of a future trial, to determine the effectiveness of the BMEA treatment for CPP in women. The primary objectives were to determine recruitment and retention rates. The secondary objectives were to assess the effectiveness of the BMEA treatment and acceptability of the study's methodology. METHODS: Women with CPP were randomised into BMEA treatment (group 1), TCM HC alone (group 2) (each intervention administered twice weekly for 4 weeks) or National Health Service standard care (NHS SC, group 3). Primary outcomes were assessed by the proportion of eligible participants randomised, and the proportion of randomised participants who returned follow-up questionnaires. Interventions were assessed by validated pain/physical/emotional functioning questionnaires at baseline (0), 4, 8 and 12 weeks. Focus groups and semi-structured telephone interviews were embedded in the study. RESULTS: A total of 30 women (51% of those referred) were randomised over 8 months. Retention rates were 80% (95% confidence interval (CI): 74-96), 53% (95% CI: 36-70) and 87% (95% CI: 63-90), in groups 1, 2, and 3, respectively. Qualitative data suggested a favourable trial experience in groups 1 and 3. DISCUSSION: Group 2 retention rate was problematic and has implications for our next trial. CONCLUSION: Our study suggests that a future trial to determine the effectiveness of BMEA treatment for women with CPP is feasible but with modifications to the study design.

A prospective validation study in South-West Nigeria on caregiver report of childhood pneumonia and antibiotic treatment using Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) questions.

BACKGROUND: Childhood pneumonia is the single largest infectious cause of death in children under five worldwide. Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) provide health information on care sought for sick children in resource poor settings. Despite not being primarily designed to identify childhood pneumonia, there are concerns that reported episodes of "symptoms of acute respiratory infection" in DHS and MICS are often interpreted by other groups as a "proxy" for childhood pneumonia. Using DHS5 and MICS5 survey tools, this study aimed to assess how accurately caregivers report of "symptoms of acute respiratory infection" reflect pneumonia episodes and antibiotic use in children under five. METHODS: Children aged 0 to 59 months presenting with cough and/or difficult breathing were recruited from four study hospitals in Ibadan, Nigeria from August 2015 to March 2017. Children were assessed using World Health Organization (WHO) standard criteria by study physicians to identify whether they had pneumonia. Three hundred and two matched children in each category of 'pneumonia' and "no pneumonia" were followed up at home, either two or eight weeks later, using questions from DHS5 and MICS5 surveys to assess the accuracy of caregiver recall of pneumonia. RESULTS: The specificity of DHS5 and MICS5 questions for identifying childhood pneumonia were 87.4 (95% confidence interval (CI) = 83.1-91.0) and 86.1 (95% CI = 81.7-89.8) respectively and the sensitivity of questions were 37.1 (95% CI = 31.6-42.8) and 37.1 (95% CI = 31.6-42.8). Correct recall of antibiotic treatment was poor (kappa statistic = 0.064) but improved with the use of medicine pill boards (kappa statistic = 0.235). CONCLUSIONS: DHS5 and MICS5 survey questions are not designed to identify childhood pneumonia and this study confirms that they do not accurately discern episodes of childhood pneumonia from cough/cold in children under five. The proportion of pneumonia episodes appropriately treated with antibiotics cannot be accurately assessed using current DHS and MICS surveys. If these results are used to guide programmatic decisions, it is likely to encourage overuse and inappropriate prescribing of antibiotics for episodes of cough/cold. International agencies who continue to use these household data to monitor the proportion of children with pneumonia who receive antibiotic treatment should be discouraged from doing this as these data are likely to mislead national and global programmes. Medicine pill boards are used in a number of DHS surveys and should be promoted for wider use in national population surveys to improve the accuracy of antibiotic recall.

Care seeking behaviour and aspects of quality of care by caregivers for children under five with and without pneumonia in Ibadan, Nigeria.

BACKGROUND: This study aimed to investigate the differences in reported care seeking behaviour and treatment between children with pneumonia and children without pneumonia with cough and/or difficult breathing. METHODS: Three hundred and two children aged 0-59 months with fast breathing pneumonia were matched with 302 children seeking care for cough and/or difficult breathing at four outpatient clinics in Ibadan, Nigeria. After follow up at home, Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) questionnaires were administered in the community by trained field workers to gather information around care seeking delay, patterns of care seeking, appropriateness of care seeking and treatment provided once care was sought. Multivariable analysis was carried out to determine significant factors associated with care seeking delay. RESULTS: Children with pneumonia had a significantly longer delay (median = 3d) before seeking care than those without pneumonia (median = 2d; P = 0.001). The length of the delay was 21% (95% confidence interval (CI) = 1%-42%) greater in those aged 0-1 month and 11% (95% CI = 5%-42%) greater in those aged 2-11 months compared to those aged 12-59 months. The length of delay was 17% (95% CI = 5%-30%) greater in rural locations than urban ones, and 33% (95% CI = 7%-51%) shorter in fathers with only primary education compared to higher education, adjusted for covariates. The range of places where care was sought showed the same distribution in those with and without pneumonia. Twenty two per cent of those with pneumonia sought care first from inappropriate providers. The number of children for whom caregivers reported having received antibiotic treatment was 92% for those with pneumonia and 84% for those without pneumonia. CONCLUSIONS: Given that children with pneumonia and cough/cold had similar patterns of reported care seeking information gathered on care seeking (type of provider visited) from DHS and MICS surveys on those with 'symptoms of acute respiratory infection' in this setting provide a reasonably valid indication of care seeking behaviours in children with pneumonia. There are high levels of antibiotic overuse for children with cough/cold in this setting which risks worsening antibiotic resistance.