A systematic review of reporting quality for anaesthetic interventions in randomised controlled trials

Interventions from randomised controlled trials can only be replicated if they are reported in sufficient detail. The results of trials can only be confidently interpreted if the delivery of the intervention was systematic and the protocol adhered to. We systematically reviewed trials of anaesthetic interventions published in 12 journals from January 2016 to September 2019. We assessed the detail with which interventions were reported, using the Consolidated Standards of Reporting Trials statement for non-pharmacological treatments. We analysed 162 interventions reported by 78 trials in 18,675 participants. Detail sufficiently precise to replicate the intervention was reported for 111 (69%) interventions. Intervention standardisation was reported for 135 (83%) out of the 162 interventions, and protocol adherence was reported for 20 (12%) interventions. Sixty (77%) out of the 78 trials reported the administrative context in which interventions were delivered and 36 (46%) trials detailed the expertise of the practitioners. We conclude that bespoke reporting tools should be developed for anaesthetic interventions and interventions in other areas such as critical care.     

Ultrathin chitosan–poly(ethylene glycol) hydrogel films for corneal tissue engineering

Due to the high demand for donor corneas and their low supply, autologous corneal endothelial cell (CEC) culture and transplantation for treatment of corneal endothelial dysfunction would be highly desirable. Many studies have shown the possibility of culturing CECs in vitro, but lack potential robust substrates for transplantation into the cornea. In this study, we investigate the properties of novel ultrathin chitosan–poly(ethylene glycol) (PEG) hydrogel films (CPHFs) for corneal tissue engineering applications. Cross-linking of chitosan films with diepoxy-PEG and cystamine was employed to prepare ～50 μm (hydrated) hydrogel films. Through variation of the PEG content (1.5–5.9 wt.%) it was possible to tailor the CPHFs to have tensile strains and ultimate stresses identical to or greater than those of human corneal tissue while retaining similar tensile moduli. Light transmission measurements in the visible spectrum (400–700 nm) revealed that the films were >95% optically transparent, above that of the human cornea (maximum ～90%), whilst in vitro degradation studies with lysozyme revealed that the CPHFs maintained the biodegradable characteristics of chitosan. Cell culture studies demonstrated the ability of the CPHFs to support the attachment and proliferation of sheep CECs. Ex vivo surgical trials on ovine eyes demonstrated that the CPHFs displayed excellent characteristics for physical manipulation and implantation purposes. The ultrathin CPHFs display desirable mechanical, optical and degradation properties whilst allowing attachment and proliferation of ovine CECs, and as such are attractive candidates for the regeneration and transplantation of CECs, as well as other corneal tissue engineering applications.     

A Prospective Study of Patient Reported Outcomes in Pancreatic and Peri-ampullary Malignancy

Background

The purpose of the present study was to describe the impact of treatment of pancreatic and peri-ampullary malignancy on patient reported outcomes (PRO). However, limited data are available describing the impact of curative or palliative therapy on pancreatic/peri-ampullary malignancy and quality of life.

Methods

Patients selected for pancreaticoduodenectomy (PD) completed the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire pre-surgery and 6 weeks, 3, 6, 12, 18, and 24 months postoperatively. Patients selected for palliative treatments completed the same questionnaire before treatment and monthly thereafter. Mean scores and 95 % confidence intervals (CI) were calculated for functional scales. Symptom scales and single items were categorized as either minimal or severe, and they were reported as proportions of patients experiencing severe symptoms with 95 % CI.

Results

A total of 100 patients (53 planned PD, 47 palliative) were enrolled. Of the 53 patients planned for surgery, 12 had tumors that were unresectable and 41 underwent pancreatoduodenectomy (PD). Seven patients were excluded because of benign histology or concurrent malignancy. Baseline questionnaire compliance was 70 %. For those undergoing PD, there were 53 complications, 7 deaths at 1 year, and 14 deaths at 2 years. Post-surgery most functions and symptoms deteriorated. Recovery in global health and most symptoms occurred by 3 months, and functional scales recovered by 6 months. Recovery of PRO was maintained in the survivors at 2 years. Palliative patients had poorer function and more symptoms at baseline; however, poor follow-up questionnaire compliance prevented further analysis of this group.

Conclusions

Pancreaticoduodenectomy has a short-term negative impact on PRO that recovers within 6 months and is maintained at 2 years in survivors. Further work evaluating palliative and curative treatment in larger patient groups with disease-specific questionnaires is necessary.     

The use of Nolvadex in the treatment of generic Tamoxifen-associated small joint arthralgia

IntroductionSmall joint arthralgia has been anecdotally reported for many years by women taking generic Tamoxifen (gT). However, it is a symptom that is absent from the side effect profile of the original Tamoxifen preparation Nolvadex. Our aim was to determine the prevalence of arthralgia in Tamoxifen users and to investigate whether it was associated with the excipient profile of the newer, generic formulations of Tamoxifen.MethodsWomen diagnosed with oestrogen receptor positive breast cancer between 2001 and 2005 were eligible. Those with new-onset arthralgia following commencement of gT were entered into a one year double crossover study. Patients were swapped from gT to Nolvadex for 6 months, the response noted, and then swapped back to gT for 6 months.ResultsOf 1020 new breast cancer patients, 918 (90%) were oestrogen receptor (OR) positive and were started on gT as part of their treatment. Of those, a total of 121 (13.2%) suffered with arthralgia. All 121 patients agreed to enter the study and swap treatment to Nolvadex for 6 months 114 patients (94.2%) had resolution of their arthralgia whilst on Nolvadex (p < 0.05).ConclusionOur findings suggest that there is an arthralgia syndrome which is prevalent in women taking generic Tamoxifen preparations. Symptoms are abolished when Nolvadex is used instead of gT. This suggests that the excipient profiles are an important factor. We hypothesise that either the excipient profile of gT induces arthralgia, or an unknown excipient of Nolvadex has a protective effect.     

Novel reversible, irreversible and fluorescent inhibitors of platelet-activating factor acetylhydrolase as mechanistic probes.

Phosphatidylcholines (1-O-alcoxy-2-amino-2-desoxy-phosphocholines and 1-pyrene-labeled analogs) were synthesized and used to examine interactions with recombinant human PAF-acetylhydrolase (PAF-AH), an enzyme purified from plasma, and with macrophage-like U937 cells. Novel phosphatidylcholines containing a sn-2-carbamoylester group such as 1-O-hexadecyl-2-desoxy-2-amino-methylcarbamoyl-2-methyl-rac-glycer o-3-phosphocholine 11 were found to act as site-specific irreversible enzyme inhibitors with Ki-values up to 83 (K(irev)) and 177 (Ki(inact)) microm. The compounds exhibit only marginal inhibition of Ca2+-dependent phospholipases. Kinetic data show that phosphocholines carrying a terminal sn-1-pyrene moiety inhibit PAF-AH activity with an effectivity similar to analogs with an aliphatic chain. 1-O-Decyloxy-[10-(4-pyrenyl)-butoxy]-2-desoxy-2-amino-carbamoyl-me thyl-rac(-glycero-3-phosphocholine 13 could be used for enzyme labeling and to demonstrate an inhibitor-enzyme stoichiometry of 0.7:1. At 8 degrees C, the compound accumulated in the membranes of U937 cells, at 37 degrees C it was internalized into intracellular compartments. Structure activity studies in a mixed micelle assay indicated that the inhibition power of reversible and irreversible inhibitors increases along with the (sn)-1-chain length similar to the structure-dependent binding of ether phospholipids to the PAF-receptor. Unlike the situation at the (sn)-1-position, increasing chain length at the sn-2-position, or an alkyl branching of the glycerol backbone significantly reduced the inhibitory potency.     

Inpatient care of small and sick newborns: a multi-country analysis of health system bottlenecks and potential solutions

Background

The Every Newborn Action Plan (ENAP) and Ending Preventable Maternal Mortality targets cannot be achieved without high quality, equitable coverage of interventions at and around the time of birth. This paper provides an overview of the methodology and findings of a nine paper series of in-depth analyses which focus on the specific challenges to scaling up high-impact interventions and improving quality of care for mothers and newborns around the time of birth, including babies born small and sick.

Methods

The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the ENAP process. Country workshops engaged technical experts to complete a tool designed to synthesise "bottlenecks" hindering the scale up of maternal-newborn intervention packages across seven health system building blocks. We used quantitative and qualitative methods and literature review to analyse the data and present priority actions relevant to different health system building blocks for skilled birth attendance, emergency obstetric care, antenatal corticosteroids (ACS), basic newborn care, kangaroo mother care (KMC), treatment of neonatal infections and inpatient care of small and sick newborns.

Results

The 12 countries included in our analysis account for the majority of global maternal (48%) and newborn (58%) deaths and stillbirths (57%). Our findings confirm previously published results that the interventions with the most perceived bottlenecks are facility-based where rapid emergency care is needed, notably inpatient care of small and sick newborns, ACS, treatment of neonatal infections and KMC. Health systems building blocks with the highest rated bottlenecks varied for different interventions. Attention needs to be paid to the context specific bottlenecks for each intervention to scale up quality care. Crosscutting findings on health information gaps inform two final papers on a roadmap for improvement of coverage data for newborns and indicate the need for leadership for effective audit systems.

Conclusions

Achieving the Sustainable Development Goal targets for ending preventable mortality and provision of universal health coverage will require large-scale approaches to improving quality of care. These analyses inform the development of systematic, targeted approaches to strengthening of health systems, with a focus on overcoming specific bottlenecks for the highest impact interventions.