Development of the Addenbrooke's MSK screening tool (AMST) for children and adolescents with cystic fibrosis.

Background: Musculoskeletal (MSK) issues are common in the paediatric population and in people with CF. There is currently no MSK screening tool for children and adolescents with CF. Methods: The protocol to develop the pGALS (paediatric Gait, Arms, Legs, Spine) was followed to create this screening tool. Paediatric respiratory and MSK physiotherapists, and paediatric respiratory doctors at a large teaching hospital were involved in the creation of this tool. This was then reviewed by paediatric respiratory doctors and physiotherapists at a second large teaching hospital with amendments added. One year data of this screening tool used on children over 7 was collected and analysed as a secondary outcome of this project. Results: There were 81.8 % more positive screens for MSK issues in the newly developed screening tool compared to the year using Manchester MSK screening tool; there were also 6 more referrals all deemed as appropriate by the services referred to. Almost half of the population screened using the developed tool were positive for an MSK issue, this was commonly related to poor posture or correctable kyphosis. Kyphosis, as measured by plumb line, appeared to be associated with negative health outcomes in this population; pectoralis major length was also associated with kyphosis and these negative health outcomes. Conclusion: The development of this tool has followed the protocol set out by the PGALs and has shown some promise with interesting initial results. This tool will need further validation before it is used in the wider paediatric CF population.

Natural history of chronic thromboembolic pulmonary disease with no or mild pulmonary hypertension.

BACKGROUND: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. METHODS: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. RESULTS: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. CONCLUSIONS: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.

Prevalence and clinical significance of conduction disease in patients with idiopathic pulmonary arterial hypertension.

Anatomical and physiological changes in the right heart as a direct consequence of the upstream pressure overload characteristic of idiopathic pulmonary hypertension (IPAH) are likely to lead to conduction disease in these patients. However, the prevalence and clinical implications of atrioventricular conduction disease in IPAH patients are not well-characterized. In this observational cohort study, we show that conduction disease is far more prevalent in a cohort of 175 IPAH patients than a group of matched comparators (37.1% vs 10.8%), and is associated with older age, male sex and more severe right heart dilatation. However, conduction disease is independently associated with worse functionality and higher mortality in this patient group. Prospective study is required to substantiate this, and whether intervention such as prophylactic pacing could restore prognosis.

Management of arrhythmias in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a potentially devastating clinical condition with a poor long-term prognosis. Cardiac arrhythmias are frequent in PH, and pulmonary hypertensives are particularly susceptible to the adverse haemodynamic effects of heart rhythm disorders. However, arrhythmia management in PH patients can be more challenging than in the general population due to the particular physiological idiosyncrasies associated with the condition. Here, we summarise and appraise the data pertaining to multimodality treatment of cardiac arrhythmias in PH to help refine the management strategy for this vulnerable patient group. RESULTS: The majority of our understanding of the safety and effectiveness of different arrhythmia treatments in PH is based on observational and retrospective data. Rhythm control is the overall goal, and for atrial and ventricular tachyarrhythmias, referral for catheter ablation, ideally using electroanatomical mapping technology in specialist centres, is the preferable means of achieving this. Contradictory viewpoints are expounded regarding the safety of beta blocker use in PH, though in three small prospective clinical trials and at least six animal models they appear to be well-tolerated. Nevertheless, amiodarone remains the preferred pharmacological treatment. Direct current cardioversion can be carried out effectively to terminate tachyarrhythmias in both the emergency and elective setting, though mechanistic studies demonstrate a higher recurrence rate in PH patients. Individual reports and series suggest that device implantation may be technically challenging and associated with a higher complication rate due to anatomical distortion and chamber enlargement. Modulation of sympathetic input to the heart appears to reduce arrhythmia vulnerability in canine models of PH, and its clinical application in humans is a worthwhile area of further study. CONCLUSION: Prompt restoration of sinus rhythm improves outcomes in PH, and at present, the most reliable and safest strategy for long-term rhythm control is amiodarone and, where possible, ablation. Reinforcement of the evidence base with randomised prospective trials is necessary. This would be particularly beneficial to clarify the role of atrial fibrillation ablation and the safety and efficacy of beta-blockers. In addition, a more comprehensive assessment of the vulnerability of PH patients to potentially fatal brady- and ventricular tachyarrhythmias may help guide recommendations for provision of primary prevention device therapy.

Safety, Feasibility and Economic Impact of Same-Day Discharge Following Atrial Fibrillation Ablation.

BACKGROUND: The widely accepted model for atrial fibrillation (AF) ablation involves overnight hospital stay post-procedure. Day case AF ablation has been carried out at Royal Papworth Hospital (RPH) since early 2017. We evaluated the feasibility, safety and efficacy of day case AF ablation at RPH. METHOD: This was a retrospective, single-centre study of consecutive AF ablations at RPH between March 2017 and April 2018. Demographic, procedural and outcome data were analysed. RESULTS: Over the study period, 452 AF ablations were performed in 448 patients. One hundred and twenty-nine (129) (28.5%) were planned day cases; of these 128 were discharged on the same day. Two hundred and eighty-three (283) procedures resulted in at least one night admission. There was no significant difference in age or sex between the groups. Of note, day case procedures were significantly shorter, more likely to commence in the morning and less likely to require general anaesthetic than overnight stays. Patients listed as day cases also had less far to travel. The overall complication rate was 3.3%, with no significant difference between groups. Follow-up data was available for 448 cases (99.1%). Procedural success rates were comparable between groups. The overall cost saving attributable to providing AF ablation as a day case was £67,200 over the 13-month period. CONCLUSIONS: Day case AF ablation is efficacious and associated with a low event rate, even without strict standardisation of patient selection or procedural protocols, in a high-volume centre. Substantial reduction in health care expenditure can be achieved with more widespread implementation of outpatient AF ablation.

Rare case of congenital chylothorax and challenges in its management.

This case describes the difficulties faced in treating recurrent pleural effusions and diagnosing chylothorax in a preterm neonate. The mother of this case was one of the first neonates to undergo in utero pleural shunting for bilateral pleural effusions 30 years ago. She then presented with an antenatal diagnosis of fetal hydrops at 31+1 weeks gestation in her own pregnancy and her baby was delivered 3 days later due to concerns about fetal distress. The baby was clinically unstable with recurrent bilateral effusions which were extensively investigated and shown to be the result of congenital chylothorax of possible genetic origin. This case demonstrates the challenges of managing chylothorax in the newborn.

Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials.

BACKGROUND: The net benefit of aspirin in prevention of CVD and nonvascular events remains unclear. Our objective was to assess the impact (and safety) of aspirin on vascular and nonvascular outcomes in primary prevention. DATA SOURCES: MEDLINE, Cochrane Library of Clinical Trials (up to June 2011) and unpublished trial data from investigators. STUDY SELECTION: Nine randomized placebo-controlled trials with at least 1000 participants each, reporting on cardiovascular disease (CVD), nonvascular outcomes, or death were included. DATA EXTRACTION: Three authors abstracted data. Study-specific odds ratios (ORs) were combined using random-effects meta-analysis. Risks vs benefits were evaluated by comparing CVD risk reductions with increases in bleeding. RESULTS: During a mean (SD) follow-up of 6.0 (2.1) years involving over 100, 000 participants, aspirin treatment reduced total CVD events by 10% (OR, 0.90; 95% CI, 0.85-0.96; number needed to treat, 120), driven primarily by reduction in nonfatal MI (OR, 0.80; 95% CI, 0.67-0.96; number needed to treat, 162). There was no significant reduction in CVD death (OR, 0.99; 95% CI, 0.85-1.15) or cancer mortality (OR, 0.93; 95% CI, 0.84-1.03), and there was increased risk of nontrivial bleeding events (OR, 1.31; 95% CI, 1.14-1.50; number needed to harm, 73). Significant heterogeneity was observed for coronary heart disease and bleeding outcomes, which could not be accounted for by major demographic or participant characteristics. CONCLUSIONS: Despite important reductions in nonfatal MI, aspirin prophylaxis in people without prior CVD does not lead to reductions in either cardiovascular death or cancer mortality. Because the benefits are further offset by clinically important bleeding events, routine use of aspirin for primary prevention is not warranted and treatment decisions need to be considered on a case-by-case basis.

Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.

BACKGROUND: Whether intensive control of glucose reduces macrovascular events and all-cause mortality in individuals with type 2 diabetes mellitus is unclear. We undertook a meta-analysis of randomised controlled trials to determine whether intensive treatment is beneficial. METHODS: We selected five prospective randomised controlled trials of 33 040 participants to assess the effect of an intensive glucose-lowering regimen on death and cardiovascular outcomes compared with a standard regimen. We gathered information about events of non-fatal myocardial infarction, coronary heart disease (fatal and non-fatal myocardial infarction), stroke, and all-cause mortality, and did a random-effects meta-analysis to obtain summary effect estimates for the clinical outcomes with use of odds ratios calculated from the raw data of every trial. Statistical heterogeneity across trials was assessed with the chi(2) and I(2) statistics. FINDINGS: The five trials provided information on 1497 events of non-fatal myocardial infarction, 2318 of coronary heart disease, 1127 of stroke, and 2892 of all-cause mortality during about 163 000 person-years of follow-up. The mean haemoglobin A(1c) concentration (HbA(1c)) was 0.9% lower for participants given intensive treatment than for those given standard treatment. Intensive glycaemic control resulted in a 17% reduction in events of non-fatal myocardial infarction (odds ratio 0.83, 95% CI 0.75-0.93), and a 15% reduction in events of coronary heart disease (0.85, 0.77-0.93). Intensive glycaemic control had no significant effect on events of stroke (0.93, 0.81-1.06) or all-cause mortality (1.02, 0.87-1.19). INTERPRETATION: Overall, intensive compared with standard glycaemic control significantly reduces coronary events without an increased risk of death. However, the optimum mechanism, speed, and extent of HbA(1c) reduction might be different in differing populations. FUNDING: None.