Is integrated private-clinic based early child development care effective? A clustered randomised trial in Pakistan

Background In Pakistan, high prevalence of delays in early child development (ECD) is associated with poverty and lack of mothers’ caregiving skills. GP clinics, the main sources of care in poor urban localities, lack quality ECD care delivery. A contextualised intervention was developed and tested to enable GPs to deliver clinic-based, tool-assisted ECD counselling of mothers on a quarterly basis. Aim To assess the effectiveness of delivering a contextualised ECD mother-counselling intervention. Design & setting Clustered randomised controlled trial, in poor urban localities of Pakistan. Locality clusters were allocated to intervention and control arm using simple randomisation. Method A total of 2327 mother–child pairs were recruited at 32 GP clinics, one from each cluster-locality; 16 GP clinics per arm. The clinic-based counselling intervention covering child stimulation, nutrition, and maternal mental health was delivered mainly by clinic assistants to mothers at ≤6 weeks, and 3, 6, and 9 months of child age. At 12 months of child age, each mother–child pair was assessed for the primary outcome, that is, delays in the five development domains (determined by Ages and Stages Questionnaire-3 [ASQ-3] score); and secondary outcomes, namely the prevalence of stunting and maternal depression (determined by Patient Health Questionnaire-9 [PHQ-9] score). The outcome assessors were blinded to the cluster–arm allocation. Outcome analyses were calculated on cluster-level. Results At 12 months, the number of children with delay in two or more development domains was significantly lower in the intervention arm (-0.17 [95% confidence interval {CI} = -0.26 to -0.09]; P<0.001) compared to the control arm. The difference in the prevalence of child stunting and maternal depression were also significant at -0.21% (95% CI = -0.30 to -0.13; P<0.001) and -0.23% (95% CI = -0.29 to -0.18; P = 0.000) respectively. Conclusion Contextualised ECD care, when delivered at GP clinics in poor urban localities, can effectively reduce the developmental delays during the first 12 months of the child's life

Effectiveness of an integrated diabetes care package at primary healthcare facilities: a cluster randomised trial in Pakistan

Background: There were an estimated 7 million people living with diabetes in Pakistan in 2014, and this is predicted to reach 11.4 million by 2030. Aim: To assess if an integrated care package can achieve better control of diabetes. Design & setting: The pragmatic cluster randomised controlled trial (cRCT) was conducted from December 2014–June 2016 at 14 primary healthcare facilities in Sargodha district. Opportunistic screening, diagnostic testing, and patient recording processes were introduced in both the control 'testing, treating, and recording' (TTR) arm, and the intervention 'additional case management' (ACM) arm, which also included a clinical care guide and pictorial flipbook for lifestyle education, associated clinician training, and mobile phone follow-up. Method: Clinics were randomised on a 1:1 basis (sealed envelope lottery method) and 250 patients recruited in the ACM arm and 245 in the TTR-only arm (age ≥25 years and HbA1c >7%). The primary outcome was mean change in HbA1c (%) from baseline to 9-month follow-up. Patients and staff were not blinded. Results: The primary outcome was available for n = 238/250 (95.2%) participants in the ACM arm and n = 219/245 (89.4%) participants in the TTR-only arm (all clusters). Cluster level mean outcome was -2.26 pp (95% confidence intervals [CI] = -2.99 to -1.53) for the ACM arm, and -1.44 pp (95% CI = -2.34 to -0.54) for the TTR-only arm. Cluster level mean ACM–TTR difference (covariate-unadjusted) was -0.82 pp (95% CI = -1.86 to 0.21; P = 0.11). Conclusion: The ACM intervention in public healthcare facilities did not show a statistically significant effect on HbA1c reduction compared to the control (TTR-only) arm. Future evaluation should assess changes after a longer follow-up period, and minimal care enhancement in the comparator (control) arm

Effectiveness of delivering integrated COPD care at public healthcare facilities: a cluster randomised trial in Pakistan

Background In Pakistan chronic obstructive pulmonary disease (COPD) prevalence is 2.1% in adults aged >40 years. Despite being a health policy focus, integrated COPD care has remained neglected, with wide variation in practice. Aim To assess whether enhanced care at public health facilities resulted in better control of COPD, treatment adherence, and smoking cessation. Design & setting A two-arm cluster randomised controlled trial was undertaken in 30 public health facilities (23 primary and 7 secondary), across three districts of Punjab, between October 2014–December 2016. Both arms had enhanced diagnosis and patient recording processes. Intervention facilities also had clinical care guides; drugs for COPD; patient education flipcharts; associated staff training; and mobile phone follow-up. Method Facilities were randomised in a 1:1 ratio (sealed envelope independent lottery method), and 159 intervention and 154 control patients were recruited. The eligibility criteria were as follows: diagnosed with COPD, aged ≥18 years, and living in the catchment area. The primary outcome was change in BODE (Body mass index, airway Obstruction, Dyspnoea, Exercise capacity) index score from baseline to final follow-up visit. Staff and patients were not blinded. Results Six-month primary outcomes were available for 147/159 (92.5%) intervention and 141/154 (91.6%) control participants (all clusters). The primary outcome results cluster-level analysis were as follows: mean intervention outcome = -1.67 (95% confidence intervals [CI] = -2.18 to -1.16); mean control outcome = -0.66 (95% CI = -1.09 to -0.22); and covariate-adjusted mean intervention–control difference = -0.96 (95% CI = -1.49 to -0.44; P = 0.001). Conclusion The findings of this trial and a separate process evaluation study support the scaling of this integrated COPD care package at primary and secondary level public health facilities in Pakistan and similar settings

Enhanced hypertension care through private clinics in Pakistan: a cluster randomised trial

Background Hypertension in Pakistan affects 33% of people aged ≥45 years, and in urban areas around 70% of basic health care occurs in private facilities. Aim To assess whether enhanced care at urban private clinics resulted in better control of hypertension, cardiovascular disease (CVD) risk factors, and treatment adherence. Design & setting A two-arm cluster randomised controlled trial was conducted at 26 private clinics (in three districts of Punjab) between January 2015–September 2016. Both arms had enhanced screening and diagnosis of hypertension and related conditions, and patient recording processes. Intervention facilities also had a clinical care guide, additional drugs for hypertension, a patient lifestyle education flipchart, associated training, and mobile phone follow-up. Method Clinics were randomised in a 1:1 ratio (sealed envelope lottery method). A total of 574 intervention and 564 control patients in 13 clusters in each arm were recruited (male and female, aged ≥25 years, systolic blood pressure [SBP] >140 mmHg, and/or diastolic blood pressure [DBP] >90 mmHg). The primary outcome was change in SBP from baseline to 9-month follow-up. Staff and patients were not blinded, but outcome assessors were blinded. Results Nine-month primary outcomes were available for 522/574 (90.9%) intervention and 484/564 (85.8%) control participants (all clusters). The unadjusted cluster-level analysis results were as follows: mean intervention outcome was -25.2 mmHg (95% confidence intervals [CI] = -29.9 to -20.6); mean control outcome was -9.4 mmHg (95% CI = 21.2 to 2.2); and mean control–intervention difference was 15.8 (95% CI = 3.6 to 28.0; P = 0.01). Conclusion The findings and separate process evaluation support the scaling of an integrated CVD–hypertension care intervention in urban private clinics in areas lacking public primary care in Pakistan

Implementation of a comprehensive intervention for patients at high risk of cardiovascular disease in rural China: A pragmatic cluster randomized controlled trial

Objective: This study aims to assess whether a standard intervention package of cardiovascular disease (CVD) care was being delivered effectively, and if it was associated with improved lifestyle and biomedical indicators. Methods: In rural China, we implemented a pragmatic cluster randomized controlled trial for 12 months, randomized at the township hospital level, and compared with usual care. Intervention case management guideline, training and performance monitoring meeting and patient support activities were designed to fit within the job description of family doctors in the township hospitals and comprised: 1) prescription of a standardised package of medicines targeted at those with hypertension or diabetes; 2) advice about specific lifestyle interventions; and 3) advice about medication adherence. Participants were 50-74 years old, had hypertension and CVD risk scores >20% or diabetes, but were excluded if a history of severe CVD events. We also randomly selected 100 participants from six selected clusters per arm as a panel to collect intermediate biomedical indicators over time. Results: A total of 28,130 participants, in 33 intervention and 34 control township hospitals, were recruited. Compared with the control arm, participants in the intervention arm had substantially improved prescribing rates of anti-hypertensives, statins and aspirin (P0.05). Conclusion: Implementation of the package by family doctors was feasible and improved prescribing and some lifestyle changes. Additional measures such as reducing medication costs and patient education are required. Trial registration: Current Controlled Trials ISRCTN58988083

Anisotropic Structure of the Order Parameter in FeSe0.45Te0.55 Revealed by Angle Resolved Specific Heat

The symmetry and structure of the superconducting gap in the Fe-based superconductors are the central issue for understanding these novel materials. So far the experimental data and theoretical models have been highly controversial. Some experiments favor two or more constant or nearly-constant gaps, others indicate strong anisotropy and yet others suggest gap zeros ("nodes"). Theoretical models also vary, suggesting that the absence or presence of the nodes depends quantitatively on the model parameters. An opinion that has gained substantial currency is that the gap structure, unlike all other known superconductors, including cuprates, may be different in different compounds within the same family. A unique method for addressing this issue, one of the very few methods that are bulk and angle-resolved, calls for measuring the electronic specific heat in a rotating magnetic field, as a function of field orientation with respect to the crystallographic axes. In this Communication we present the first such measurement for an Fe-based high-Tc superconductor (FeBSC). We observed a fourfold oscillation of the specific heat as a function of the in-plane magnetic field direction, which allowed us to identify the locations of the gap minima (or nodes) on the Fermi surface. Our results are consistent with the expectations of an extended s-wave model with a significant gap anisotropy on the electron pockets and the gap minima along the \Gamma M (or Fe-Fe bond) direction.Comment: 32 pages, 7 figure

Effect of a training and educational intervention for physicians and caregivers on antibiotic prescribing for upper respiratory tract infections in children at primary care facilities in rural China: a cluster-randomised controlled trial

Background: Inappropriate antibiotic prescribing contributes to the generation of drug resistance worldwide, and is particularly common in China. We assessed the effectiveness of an antimicrobial stewardship programme aiming to reduce inappropriate antibiotic prescribing in paediatric outpatients by targeting providers and caregivers in primary care hospitals in rural China. Methods: We did a pragmatic, cluster-randomised controlled trial with a 6-month intervention period. Clusters were primary care township hospitals in two counties of Guangxi province in China, which were randomly allocated to the intervention group or the control group (in a 1:1 ratio in Rong county and in a 5:6 ratio in Liujiang county). Randomisation was stratified by county. Eligible participants were children aged 2–14 years who attended a township hospital as an outpatient and were given a prescription following a primary diagnosis of an upper respiratory tract infection. The intervention included clinician guidelines and training on appropriate prescribing, monthly prescribing peer-review meetings, and brief caregiver education. In hospitals allocated to the control group, usual care was provided, with antibiotics prescribed at the individual clinician's discretion. Patients were masked to their allocated treatment group but doctors were not. The primary outcome was the antibiotic prescription rate in children attending the hospitals, defined as the cluster-level proportion of prescriptions for upper respiratory tract infections in 2–14-year-old outpatients, issued during the final 3 months of the 6-month intervention period (endline), that included one or more antibiotics. The outcome was based on prescription records and analysed by modified intention-to-treat. This study is registered with the ISRCTN registry, number ISRCTN14340536. Findings: We recruited all 25 eligible township hospitals in the two counties (14 hospitals in Rong county and 11 in Liujiang county), and randomly allocated 12 to the intervention group and 13 to the control group. We implemented the intervention in three internal pilot clusters between July 1, 2015, and Dec 31, 2015, and in the remaining nine intervention clusters between Oct 1, 2015 and March 31, 2016. Between baseline (the 3 months before implementation of the intervention) and endline (the final 3 months of the 6-month intervention period) the antibiotic prescription rate at the individual level decreased from 82% (1936/2349) to 40% (943/2351) in the intervention group, and from 75% (1922/2548) to 70% (1782/2552) in the control group. After adjusting for the baseline antibiotic prescription rate, stratum (county), and potentially confounding patient and prescribing doctor covariates, this endline difference between the groups represented an intervention effect (absolute risk reduction in antibiotic prescribing) of −29% (95% CI −42 to −16; p=0·0002). Interpretation: In China's primary care setting, pragmatic interventions on antimicrobial stewardship targeting providers and caregivers substantially reduced prescribing of antibiotics for childhood upper respiratory tract infections. Funding: Department of International Development (UKAID) through Communicable Diseases Health Service Delivery

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients

Can renal and bladder ultrasound replace CT urogram in patients investigated for microscopic hematuria?

PURPOSE: Computed tomography urogram (CTU) is recommended when investigating patients with hematuria. We determine the incidence of urinary tract cancer and compare the diagnostic accuracy of CTU and renal and bladder ultrasound (RBUS) at identifying urinary tract cancer. METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) is a prospective observational study recruiting patients ≥18 years following a presentation of macroscopic or microscopic haematuria at 40 hospitals. All patients had cystoscopy and upper tract imaging (CTU, RBUS or both). RESULTS: 3,556 patients with a median age of 68 years were recruited, of which 2166 had RBUS and 1692 had CTU in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer (UTUC) were 11.0%, 1.4% and 0.8% respectively in macroscopic hematuria patients. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and UTUC respectively. The sensitivity and negative predictive value (NPV) of RBUS for the detection of renal cancer was 85.7% and 99.9% respectively but 14.3% and 99.7% for the detection of UTUC. RBUS was poor at identifying renal calculi. Sensitivity of RBUS was lower than CTU for the detection of bladder cancer (both <85%). Cystoscopy has a specificity and PPV of 98.3% and 83.9% respectively. CONCLUSION: CTU can be safely replaced with RBUS in patients with microscopic hematuria. The incidence of UTUC is 0.8% in patients with macroscopic hematuria and CTU is recommended. Patients with suspected renal calculi will require non-contrast renal tract CT. Imaging cannot replace cystoscopy to diagnose bladder cancer