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Relationship between primary school healthy eating and physical activity promoting environments and children's dietary intake, physical activity and weight status: a longitudinal study in the West Midlands, UK.
No full textOBJECTIVE
We aimed to examine the association between food and physical activity environments in primary schools and child anthropometric, healthy eating and physical activity measures.
DESIGN
Observational longitudinal study using data from a childhood obesity prevention trial.
SETTING
State primary schools in the West Midlands region, UK.
PARTICIPANTS
1392 pupils who participated in the WAVES (West Midlands ActiVe lifestyle and healthy Eating in School children) childhood obesity prevention trial (2011-2015).
PRIMARY AND SECONDARY OUTCOME MEASURES
School environment (exposure) was categorised according to questionnaire responses indicating their support for healthy eating and/or physical activity. Child outcome measures, undertaken at three time points (ages 5-6, 7-8 and 8-9 years), included body mass index z-scores, dietary intake (using a 24-hour food ticklist) and physical activity (using an Actiheart monitor over 5 days). Associations between school food and physical activity environment categories and outcomes were explored through multilevel models.
RESULTS
Data were available for 1304 children (94% of the study sample). At age 8-9 years, children in 10 schools with healthy eating and physical activity-supportive environments had a higher physical activity energy expenditure than those in 22 schools with less supportive healthy eating/physical activity environments (mean difference=5.3 kJ/kg body weight/24 hours; p=0.05). Children in schools with supportive physical activity environments (n=8) had a lower body mass index z-score than those in schools with less supportive healthy eating/physical activity environments (n=22; mean difference=-0.17, p=0.02). School food and physical activity promoting environments were not significantly associated with dietary outcomes.
CONCLUSIONS
School environments that support healthy food and physical activity behaviours may positively influence physical activity and childhood obesity.
TRIAL REGISTRATION NUMBER
ISRCTN97000586
Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19.
No full textAngiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients. We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed. Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders ( < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate ( < 0.0001) and mild ( = 0.0002) histologically active disease. Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD
Ixazomib, lenalidomide, and dexamethasone is effective and well tolerated in multiply relapsed (≥2nd relapse) refractory myeloma: a multicenter real world UK experience.
No full textThere are limited real world data on ixazomib, lenalidomide, and dexamethasone (IRd) in multiply relapsed myeloma. We analyzed outcomes of 116 patients who received IRd predominantly at second and subsequent relapse including those refractory to proteasome inhibitors (PIs). With a median follow up 16.3 months, the overall response rate was 66.9%; median progression-free survival (PFS) was 17.7 months with median overall survival (OS) not reached (NR). PFS and OS were significantly shorter in advanced disease (PFS; 12.6 vs. 21.2 months ( = .01), OS; 15.9 months vs. NR ( = .01) for ISS3 vs. ISS 1&2, respectively). PFS and OS were significantly shorter in clinical high risk (CHR) compared to standard risk (SR) patients (PFS; 9.3 months vs. NR ( = .001), OS; 11.5 months vs. NR ( < .001), respectively). There was a trend toward shorter PFS in PI-refractory patients 13.7 vs. 19.6 months for non-PI refractory ( = .2). The triplet combination was generally well tolerated
Multimodality Imaging in Secondary Mitral Regurgitation.
No full textSecondary mitral regurgitation (sMR) is characterized by left ventricular (LV) dilatation or dysfunction, resulting in failure of mitral leaflet coaptation. sMR complicates up to 35% of ischaemic cardiomyopathies (1) and 57% of dilated cardiomyopathies (2). Due to the prevalence of coronary artery disease worldwide, ischaemic cardiomyopathy is the most frequently encountered cause of sMR in clinical practice. Although mortality from cardiovascular disease has gradually fallen in Western countries, severe sMR remains an independent predictor of mortality (3) and hospitalization for heart failure (4). The presence of even mild sMR following acute MI reduces long-term survival free of major adverse events (1). Such adverse outcomes worsen as the severity of sMR increases, due to a cycle in which LV remodeling begets sMR and vice versa. Current guidelines do not recommend invasive treatment of the sMR alone as a first-line approach, due to the paucity of evidence supporting improvement in clinical outcomes. Furthermore, a lack of international consensus on the thresholds that define severe sMR has resulted in confusion amongst clinicians determining whether intervention is warranted (5, 6). The recent Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial (7) assessing the effectiveness of transcatheter mitral valve repair is the first study to demonstrate mortality benefit from correction of sMR and has reignited interest in identifying patients who would benefit from mitral valve intervention. Multimodality imaging, including echocardiography and cardiovascular magnetic resonance (CMR), plays a key role in helping to diagnose, quantify, monitor, and risk stratify patients for surgical and transcatheter mitral valve interventions
Validation of an extended total joint replacement (eTJR) classification system for the temporomandibular joint (TMJ).
No full textThe aim of this paper was to validate a previously described classification system for extended total joint replacements (eTJRs) of the temporomandibular joint (TMJ). We engaged an expert panel to review 60 TMJ eTJR devices and classify them using the system, examining their responses for inter-rater agreement and concordance with the correct response as determined by the authors. Conger's kappa was 0.34 for the fossa (F) component sub-classification and 0.67 for the mandibular (M) component. A posthoc analysis showed improvements in inter-rater agreement for a modified three-tiered F sub-classification system which is suggested in a revised version of the TMJ eTJR classification system
Performance measures in inflammatory bowel disease surveillance colonoscopy: Implementing changes to practice improves performance.
No full textBACKGROUND AND AIM
Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for inflammatory bowel disease (IBD) surveillance. However, DCE has not yet been widely adopted into clinical practice. We evaluated quality indicators in IBD surveillance following introduction of structured changes in service delivery.
METHODS
In August 2016, we introduced a number of changes to IBD surveillance practice in our endoscopy unit. These included training using interactive videos/images in a structured module, DCE as standard by using a foot-pedal operated pump jet, allocation of 45-minute procedure timeslots, targeted biopsies (except in high-risk patients), scoring of endoscopic disease activity, and lesion detection/morphology characterization. All IBD surveillance colonoscopies were allocated to a small team of four DCE-trained endoscopists. We compared quality measures for surveillance procedures carried out pre- and post-August 2016. The two groups were compared using chi-squared statistics RESULTS: A total of 598 IBD surveillance procedures (277 pre-August 2016 and 321 post-August 2016) were done and included in the study. Use of DCE increased (54.2% vs 76.0% P < 0.0005) whereas random biopsy surveillance decreased (12.3% vs 3.1% P < 0.0005). Use of Paris classification (26.1% vs 57.0% P < 0.0005) and Kudo pit pattern increased (21.7% vs 59.0% P < 0.0005). There was also an increase in lesion detection rate (24.9% vs 33.1% P < 0.05).
CONCLUSIONS
Implementation of extensive changes in practice of surveillance colonoscopy resulted in significant improvement in quality indicators within a short period of time. Training, education and audit may continue to facilitate the adoption of DCE and further improve quality of performance in IBD surveillance
Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.
No full textBACKGROUND
The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression.
METHODS
We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020).
INTERPRETATION
These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy.
FUNDING
Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society
Congenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant.
No full textCongenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of disorders caused by mutations which lead to impaired neuromuscular transmission. SLC25A1 encodes a mitochondrial citrate carrier, associated mainly with the severe neurometabolic disease combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). We previously reported a single family with a homozygous missense variant in SLC25A1 with a phenotype restricted to relatively mild CMS with intellectual disability, but to date no additional cases of this CMS subtype had been reported. Here, we performed whole exome sequencing (WES) in three additional and unrelated families presenting with CMS and mild intellectual disability to identify the underlying causative gene. The WES analysis revealed the presence of a homozygous c.740G>A; p.(Arg247Gln) missense SLC25A1 variant, the same SLC25A1 variant as identified in the original family with this phenotype. Electron microscopy of muscle from two cases revealed enlarged and accumulated mitochondria. Haplotype analysis performed in two unrelated families suggested that this variant is a result of recurrent mutation and not a founder effect. This suggests that p.(Arg247Gln) is associated with a relatively mild CMS phenotype with subtle mitochondrial abnormalities, while other variants in this gene cause more severe neurometabolic disease. In conclusion, the p.(Arg247Gln) SLC25A1 variant should be considered in patients presenting with a presynaptic CMS phenotype, particularly with accompanying intellectual disability
Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey.
No full textBACKGROUND & AIMS
The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF).
METHODS
In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions.
RESULTS
HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001).
CONCLUSIONS
This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care