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The Effect of Postoperative Analgesia on the Day-Case Rate of Laparoscopic Cholecystectomy: A Randomised Pilot Study of the Laparoscopic-Assisted Right Subcostal Transversus Abdominis Plane Block plus Local Anaesthetic Wound Infiltration versus Local Anaesthetic Wound Infiltration only
No full textOBJECTIVE: The transversus abdominis plane (TAP) block and local anaesthetic infiltration (LAI) of port sites provide adequate analgesia after laparoscopic cholecystectomy (LC). Little is known if the two techniques affect the day-case (DC) rate of LC. We tested the appropriateness of the research design in view of a larger randomised controlled trial (RCT) - laparoscopic-assisted right subcostal TAP block plus local anaesthetic wound infiltration (STALA) versus LAI. SUBJECTS AND METHODS: Sixty patients having DC LC were randomised into STALA and LAI. Participants received bupivacaine 0.5% 30 mL. Pain scores were evaluated with the Visual Analogue Scale (VAS) score, at 1 h post-surgery and at discharge. Need of postoperative intravenous (IV) opioids, DC rate, and Quality of Recovery-15 questionnaires were compared between groups and were considered as measures of efficacy of the interventions and follow-up in a definitive trial. RESULTS: Twenty-nine participants were randomised to STALA, and 31 to LAI. Subjects in LAI group were all women (p = 0.0007) and younger (43.8 vs. 37.7 years, p = 0.023). Median VAS scores were 0 versus 1 at 1 h (p = 0.60), 0 versus 1.5 at discharge (p = 0.55). The need of IV opioids was 15/29 (51.7%) versus 13/31 (41.9%; p = 0.60). The DC rate was 93.1% versus 93.5% (p = 0.39). Fifty (83.3%) participants responded the questionnaires. CONCLUSIONS: The laparoscopically guided right subcostal TAP block provided no additional benefit to LAI on pain control after LC and DC rate. Despite the appropriate design, our findings do not support a larger RCT.This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Something that helped the whole picture': Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service
No full textOBJECTIVES: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. METHODS: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. CONCLUSION: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care.Published version, accepted version (12 month embargo)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results
No full textOBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD. DESIGN: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence. RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180. CONCLUSION: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested. TRIAL REGISTRATION NUMBER: ISRCTN41353774.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Development and pilot testing of a patient-reported outcome measure to assess symptoms of parastomal hernia
No full textAIM: The aim was to develop and pilot a patient-reported outcome measure (PROM) to assess symptoms of parastomal hernia (PSH). METHODS: Standard questionnaire development was undertaken (phases 1-3). An initial list of questionnaire domains was identified from validated colorectal cancer PROMs and from semi-structured interviews with patients with a PSH and health professionals (phase 1). Domains were operationalized into items in a provisional questionnaire, and 'think-aloud' patient interviews explored face validity and acceptability (phase 2). The updated questionnaire was piloted in patients with a stoma who had undergone colorectal surgery and had a computed tomography scan available for review. Patient-reported symptoms were examined in relation to PSH (phase 3). Three sources determined PSH presence: (i) data about PSH presence recorded in hospital notes, (ii) independent expert review of the computed tomography scan and (iii) patient report of being informed of a PSH by a health professional. RESULTS: For phase 1, 169 and 127 domains were identified from 70 PROMs and 29 interviews respectively. In phase 2, 14 domains specific to PSH were identified and operationalized into questionnaire items. Think-aloud interviews led to three minor modifications. In phase 3, 44 completed questionnaires were obtained. Missing data were few: 5/660 items. PSH symptom scores associated with PSH presence varied between different data sources. The scale with the most consistent differences between PSH presence and absence and all data sources was the stoma appearance scale. CONCLUSION: A PROM to examine the symptoms of PSH has been developed from the literature and views of key informants. Although preliminary testing shows it to be understandable and acceptable it is uncertain if it is sensitive to PSH-specific symptoms and further psychometric testing is needed.Accepted version (12 month embargo)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial
No full textBACKGROUND: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. METHODS: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m(2) for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m(2) for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. FINDINGS: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. INTERPRETATION: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. FUNDING: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Patient-centred composite scores as tools for assesment of response to biological therapy for paediatric and adult severe asthma
No full textBACKGROUND: We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL). METHODS: International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity. RESULTS: Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001)). CONCLUSIONS: We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Expanding the genetic spectrum of hereditary motor sensory neuropathies in Pakistan
No full textBACKGROUND: Hereditary motor and sensory neuropathy (HMSN) refers to a group of inherited progressive peripheral neuropathies characterized by reduced nerve conduction velocity with chronic segmental demyelination and/or axonal degeneration. HMSN is highly clinically and genetically heterogeneous with multiple inheritance patterns and phenotypic overlap with other inherited neuropathies and neurodegenerative diseases. Due to this high complexity and genetic heterogeneity, this study aimed to elucidate the genetic causes of HMSN in Pakistani families using Whole Exome Sequencing (WES) for variant identification and Sanger sequencing for validation and segregation analysis, facilitating accurate clinical diagnosis. METHODS: Families from Khyber Pakhtunkhwa with at least two members showing HMSN symptoms, who had not previously undergone genetic analysis, were included. Referrals for genetic investigations were based on clinical features suggestive of HMSN by local neurologists. WES was performed on affected individuals from each family, with Sanger sequencing used to validate and analyze the segregation of identified variants among family members. Clinical data including age of onset were assessed for variability among affected individuals, and the success rate of genetic diagnosis was compared with existing literature using proportional differences and Cohen's h. RESULTS: WES identified homozygous pathogenic variants in GDAP1 (c.310 + 4 A > G, p.?), SETX (c.5948_5949del, p.(Asn1984Profs*30), IGHMBP2 (c.1591 C > A, p.(Pro531Thr) and NARS1 (c.1633 C > T, p.(Arg545Cys) as causative for HMSN in five out of nine families, consistent with an autosomal recessive inheritance pattern. Additionally, in families with HMSN, a SETX variant was found to cause cerebellar ataxia, while a NARS1 variant was linked to intellectual disability. Based on American College of Medical Genetics and Genomics criteria, the GDAP1 variant is classified as a variant of uncertain significance, while variants in SETX and IGHMBP2 are classified as pathogenic, and the NARS1 variant is classified as likely pathogenic. The age of onset ranged from 1 to 15 years (Mean = 5.13, SD = 3.61), and a genetic diagnosis was achieved in 55.56% of families with HMSN, with small effect sizes compared to previous studies. CONCLUSIONS: This study expands the molecular genetic spectrum of HMSN and HMSN plus type neuropathies in Pakistan and facilitates accurate diagnosis, genetic counseling, and clinical management for affected families.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Can Cemented Femoral Stems Be Used During Revision Total Hip Arthroplasty?
No full textRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Efficacy and Safety of Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials
No full textHypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options. This meta-analysis aims to evaluate the efficacy and safety of CMIs in HCM patients. PubMed/MEDLINE, Embase, the Cochrane Library, Ovid, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared CMIs to control treatments in HCM patients from inception till June 15, 2024. A random-effects model was used to pool odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes along with the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the χ2 test and Higgins I2 statistic, and sensitivity and subgroup analyses were performed. Six RCTs involving 826 patients were included. CMI therapy significantly reduced resting left ventricular outflow tract (LVOT) gradient (MD, -37.64; 95% CI, -46.71 to -28.56), Valsalva LVOT gradient (MD, -46.04; 95% CI, -57.60 to -34.48), post-exercise LVOT peak gradient (MD, -48.64; 95% CI, -68.20 to -28.88), N-terminal pro-b-type natriuretic peptide levels (MD, -1.05; 95% CI, -1.64 to -0.47), and cardiac troponin I levels (MD, -7.96; 95% CI, -12.84 to -3.07). Improvements were observed in peak oxygen consumption (MD, 1.20; 95% CI, 0.23-2.17) and patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score: MD, 6.44; 95% CI, 3.50-9.37), with more patients achieving New York Heart Association class improvement >1 (OR, 4.05; 95% CI, 2.61-6.30). Treatment-emergent adverse events were higher with CMI therapy (OR, 1.45; 95% CI, 1.02-2.05), but serious adverse events and other safety outcomes were comparable in both groups. CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies.Not hel
Challenges in developing and implementing international best practice guidance for intermediate-risk variants in cancer susceptibility genes: APC c.3920T>A p.(Ile1307Lys) as an exemplar
No full textPublished version, accepted version, submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted