Laparoscopic cholecystectomy performed by a surgical care practitioner: a review of outcomes.

INTRODUCTION: Surgical care practitioners (SCPs) are non-medical workers involved in various aspects of the management of surgical patients. The role includes assisting and performing surgical procedures. More than 60,000 laparoscopic cholecystectomies (LC) are performed annually in the UK. With ever-increasing pressure on waiting lists, it is important to look at fully utilising the skills of our entire workforce. We report what we believe is the first published series of LC performed by an SCP. METHODS: A retrospective review of a prospectively collected database was performed. The primary outcome was any complication requiring intervention. Secondary outcomes were minor complications, operative time, length of stay, conversion and readmission. RESULTS: In total, 170 patients were operated on. Indications were biliary colic in 127 (74.7%), cholecystitis in 30 (17.6%) and pancreatitis in 13 (7.6%). Mean operating time was 65min (range 35-152min). Fifty-three operations were assisted by a consultant, 110 by a specialist or associate specialist grade (SAS) doctor and 7 by a core trainee (CT2). Some 139 (81.7%) patients were discharged on the day of surgery and 24 (14.1%) stayed one night in hospital. There were no major complications. Five patients required readmission, three with pain and two with port site infections. There were no conversions or transfusions required. CONCLUSIONS: There is a paucity of published data on surgical outcomes of procedures performed by SCPs. With a structured, supervised approach, SCPs could be trained to take on more complex procedures and further strengthen the surgical workforce. This study demonstrates that elective LC can be safely performed by an appropriately trained and supervised SCP.

Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047].

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for PSA failure. METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, pre-op PSA≥10ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ("Adjuvant-RT") or an observation policy with salvage RT for PSA failure ("Salvage-RT") defined as PSA≥0.1ng/ml or 3 consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5Gy/20 fractions or 66Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant metastasis, designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10yr with Adjuvant-RT. Secondary outcome measures were bPFS, freedom-from-non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; HR<1 favours Adjuvant-RT. FINDINGS: Between Oct-2007 and Dec-2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with median age 65yr. 93% (649/697) Adjuvant-RT reported RT within 6m after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10yr FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 (95%CI 0·43-1·07, p=0·095). Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95%CI 0.667-1.440, p=0.917). Adjuvant-RT reported worse urinary and faecal incontinence one year after randomisation (p=0.001); faecal incontinence remained significant after ten years (p=0.017). INTERPRETATION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy.

Long term outcomes of nonmyeloablative allogeneic stem cell transplantation with TSEB TLI and ATG for Mycosis Fungoides and Sezary Syndrome.

Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.

Patient Outcomes Are Not Improved by Platelet-Rich Plasma Injection Onto the Capsule at the Time of Closure During Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Purpose: To determine the effect of platelet-rich plasma (PRP) injection onto the capsule at time of closure on outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. Methods: Patients who underwent hip arthroscopy between January 2014 and December 2021 were retrospectively identified. The first cohort included patients who received PRP injection onto the capsule following capsular closure at the conclusion of the case. The second cohort did not receive PRP. Pain scores on a visual analog scale, Modified Harris Hip Scores, Single Assessment Numeric Evaluation (SANE), as well as Patient-Reported Outcomes Measurement Information System Physical Function scores were obtained preoperatively as well as at multiple time points postoperatively up to 2 years. Results: In total, 345 patients were included in the study, with 293 in the PRP cohort and 52 in the non-PRP cohort. There was no significance difference in age (P = .69), sex, or preoperative pain (P = .92) and patient-reported outcome scores between the 2 groups (modified Harris Hip Score, P = .38; Patient-Reported Outcomes Measurement Information System Physical Function, P = .48), except for preoperative SANE scores, which had a greater baseline in the PRP group (P < .001). Using both observed data as well as repeated measure analysis of variance model to estimate for missing data after baseline, we found there were no differences in visual analog scale pain scores nor patient-reported outcome scores at any time point. There was similarly no difference in change from baseline for SANE scores. There was no difference in rate of revision surgery between the 2 cohorts (P = .66). Conclusions: Based on the results of this study, intraoperative PRP injection onto the capsule at the time of capsular closure does not improve outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. Level of Evidence: Level III, retrospective comparative study.

Two cases of MPXV infection during pregnancy in heterosexual cisgender women without classic cutaneous lesions, Northern California, 2022.

As part of an epidemiologic survey, we screened remnant samples collected for STI testing for mpox virus. We identified two cases of presumed MPXV infection in pregnant, heterosexual cisgender women. Here, we describe their pregnancy and birth outcomes. Both patients required induction of labor and experienced labor complicated by chorioamnionitis.

A Longitudinal Study of Journal Club to Enhance Physical Therapy Students' Research Appraisal Skill for Evidence-Based Practice: A Mixed-Methods Study.

Evidence-based practice (EBP) requires that clinicians possess skills in appraisal of evidence. Journal club (JC) is demonstrated to increase EBP skills in medicine, nursing, and occupational therapy. Study in physical therapy remains elusive. The objective of this study was to examine the impact of JC on appraisal skills in student physical therapists (SPTs) and explore factors enhancing or hindering the utility of JC. One hundred fifteen SPTs from three cohorts participated in this mixed-methods study. In the first year, participants completed a survey assessing self-reported confidence level on EBP skills before and after attending multiple JCs. Cohorts I and II continued participation in the second year. Additionally, 36 participants attended focus-group interviews after completing 2 years of JC. All cohorts' confidence level increased. Wilcoxon signed-rank test revealed a significant increase (p < 0.001) for cohort III. Remaining cohorts' confidence continuously increased in the subsequent year. Thematic analysis revealed themes on benefits and barriers of JC, strategies for improvements, and connection of JC to clinical practice. The findings indicate that integration of JC promotes SPTs' confidence in EBP skills and connects with practice. Utilizing JC as a pedagogical strategy impacts curricular design and strengthens future health professionals' EBP skills pivotal for delivering quality healthcare.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Prevalence of Mpox (Monkeypox) in patients undergoing STI screening in northern California, April-September 2022.

BACKGROUND: Despite the sharp increase in mpox (formerly monkeypox) incidence and the wide geographic spread of mpox during the 2022 outbreak, the community prevalence of infection remains poorly characterized. This study is a retrospective epidemiologic survey to estimate mpox prevalence. METHODS: Samples obtained for sexually transmitted infection (STI) testing from April to September 2022 in the public hospital and clinic system of San Mateo County, California were screened for mpox virus (MPXV) using polymerase chain reaction. RESULTS: 16/1,848 samples from 11/1,645 individuals were positive for MPXV by qPCR. 4/11 individuals with positive MPXV testing were cisgender women, 2 of whom were pregnant at the time of sample collection. Both deliveries were complicated by chorioamnionitis. Anorectal and oropharyngeal samples were the most likely to be positive for MPXV (4/60 anorectal samples and 4/66 oropharyngeal samples compared with 5/1,264 urine samples and 3/445 vaginal samples). CONCLUSIONS: Our study is one of the first epidemiologic surveys for MPXV infection outside of sexual health/STI clinic settings. Relatively high rates of MPXV from oropharyngeal and anorectal samples reinforces the importance of MPXV testing at various anatomic sites, particularly if patients are presenting with non-lesional symptoms (pharyngitis, proctitis). However, the United States Food and Drug Administration (FDA) has not yet authorized non-lesional MPXV testing. The identification of MPXV in women in our cohort suggests that the rates of mpox in women may have previously been underestimated and highlights the risk of pregnancy complications associated with mpox.

Osteoarthritis consumers as co-researchers: identifying consumer insights to improve osteoarthritis management by co-designing translational research solutions.

INTRODUCTION: Co-design is a consumer-driven approach that facilitates consumer participation in creating meaningful solutions to complex problems. Poor uptake of core management strategies for osteoarthritis suggests there is a missing link in translation between research and practice. We partnered with osteoarthritis consumers as 'co-researchers' to identify translational research solutions to improve uptake of core management strategies that are grounded in lived experiences. OBJECTIVE: To transparently describe a theory-driven, generative co-design approach using an integrated conceptual framework to collaborate with consumers at the equal partnership level. DESIGN: We used co-design workshops with a non-hierarchical participatory framework. Three workshops with six co-researchers [2 female, mean age 68.7 (9.8) years, 3-30 years symptom duration] were conducted using activities to encourage creative thinking, promote deep reflection on personal/societal beliefs and minimise sensitivities around sharing personal beliefs (e.g., establishing a safe space, prompting questions, perspective-taking, counter-stereotypical exemplars). RESULTS: All six co-researchers actively participated in the workshops. Achievement of an equal collaborative partnership was evidenced by co-researchers challenging a project proposed by the research team and making alternative recommendations that have been implemented in prospective decision-making - representing a complete change in research focus driven by consumer input. A key suggested solution was to develop a scalable knowledge translation intervention that targets misconceptions about osteoarthritis and its management at the societal-level. CONCLUSIONS: Through an innovative co-design approach in partnership with co-researchers, we identified meaningful areas on which to focus translational research for osteoarthritis. Discordance between existing research priorities and novel solutions proposed by co-researchers highlights the value of co-design.

The impact of having a carer on adult health and social care utilisation across five settings of care: A matched cohort study.

INTRODUCTION: An estimated 6.8 million people are (informal) carers in the UK. The economic value of annual carer contributions is an estimated .·132bn. Reliance on carers appears to be increasing. There is mixed evidence on whether carers are substitutes for formal care. This study investigated the association between having a carer and service use patterns across five care settings when compared to a matched cohort without a carer. MATERIALS AND METHODS: A matched case-control group analysis using person-level data in Barking and Dagenham (B&D), a London borough in the U.K., to assess the impact of having a carer in terms of the differences in cost-weighted utilisation relative to a matched control group. RESULTS: In 2016/17, for adult residents of B&D, having a carer (n = 1,295) was associated with 27% increased cost-weighted utilisation (mean difference of £2,662, CI £1,595, £3,729, p<0.001) compared to a matched cohort without a carer. 39% of the cost difference was social care. CONCLUSIONS: Findings suggest additional service use induced by carers may dominate any substitution effect. Having a carer may be a key element in enabling access to services. As such, there may be wider inequalities in service access for people without a carer. For an ageing society with projections suggesting there will be more people without carers in the future, these inequalities need to be addressed.

Paediatric quality-of-life following adenotonsillectomy: an evaluation of T14 paediatric throat disorder quality-of-life outcomes according to operative indication.

INTRODUCTION: Adenotonsillectomy is the most common surgical intervention for obstructive sleep apnoea (OSA) or recurrent tonsillitis. The Paediatric Throat Disorder Quality of Life Outcome (T14) questionnaire is a validated tool completed by parents to compare the outcome of surgery by measuring the pre- and postoperative scores. This study was undertaken to evaluate the quality-of-life outcome in children undergoing surgical intervention for recurrent tonsillitis and/or OSA. METHODS: This was a prospective, uncontrolled study of 117 children who underwent adenotonsillectomy and tonsillectomy at a single tertiary ear, nose and throat department. An analysis of pre- and postoperative T14 paediatric throat disorder quality-of-life outcomes was undertaken at 12 months. RESULTS: Of the 117 children, 105 were included in the study sample; 75 with recurrent tonsillitis, 8 with OSA and 22 with both tonsillitis and OSA. All children had an improved T14 score postoperatively. The greatest change in pre- and postoperative T14 score was observed in the tonsillitis and OSA combined group (mean change -29.36, p<0.001). However, an improvement in T14 score was also noted in the tonsilitis (-24.453, p<0.001) and OSA groups (-14.25, p<0.001). CONCLUSIONS: This study found a statistically significant improvement in the T14 quality-of-life score at 12 months postoperatively in children undergoing adenotonsillectomy. This demonstrates improved parental perception of their child's symptoms for all operative indications of adenotonsillectomy.

Symptoms of sleep disordered breathing: Association with the apnea-hypopnea index and somatic arousal.

We investigated the association of typical symptoms of obstructive sleep apnea with a measure of daytime somatic arousal and with the apnea-hypopnea index. We extended the finding of an association between sleepiness, fatigue and somatic arousal previously reported in a US sleep apnea population to a German sleep apnea population (n = 374) and to other typical sleep apnea symptoms, insomnia, anxiety, daytime alertness and non-restorative sleep. Somatic arousal was measured using the body sensation questionnaire (BSQ). Correlations of apnea-hypopnea index and BSQ were computed with values of polysomnographic variables derived from overnight sleep studies and with severity of OSA symptoms. Apnea-hypopnea index and BSQ scores showed only a small negative correlation with each other; each correlated independently with the Epworth Sleepiness Scale score. Controlling for BSQ score, the apnea-hypopnea index was found to affect sleepiness only when it exceeded 50/h. Severity of all other sleep apnea symptoms did not increase with increasing apnea-hypopnea index. In contrast, severity of all symptoms of sleep apnea increased consistently with increasing BSQ scores. Thus, autonomic stress associated with obstructive sleep apnea may be the driving force behind sleep apnea symptoms rather than the sleep fragmentation associated with obstructive sleep apnea severity (apnea-hypopnea index). These findings support previously reported correlations by Gold and associates between the levels of somatic arousal, sleepiness and fatigue. Using the apnea-hypopnea index and BSQ together renders a more comprehensive assessment of sleep apnea than apnea-hypopnea index alone, which appears to impact only on sleepiness and only when it exceeds 50/h. More work is needed to elucidate the source of the chronic stress, which appears to arise endogenously in affected individuals, likely as a function of sleep disordered breathing, such as snoring/inspiratory flow limitation.

Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization.

An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes.

A comparison of the kinematics and kinetics of barefoot and shod running in children with cerebral palsy.

BACKGROUND: The biomechanics of barefoot and shod running are different for typically developing children but unknown for children with cerebral palsy (CP). Such differences may have implications for injury and performance. AIMS: The primary aims of this study were to compare the lower limb biomechanics of barefoot and shod running in children with CP, and to determine whether any differences were the same in GMFCS levels I and II. METHODS: This cross-sectional study examined 38 children with CP (n = 24 (GMFCS) level I; n = 14 GMFCS II), running overground at 3 speeds (jog, run, sprint) in barefoot and shod conditions. Marker trajectories and force plate data were recorded, and lower limb kinematics, kinetics and spatiotemporal variables were derived. Differences between barefoot and shod running were analysed using linear mixed models. RESULTS: For both GMFCS levels, barefoot running resulted in higher loading rates, but smaller impact peaks at all speeds. Barefoot running was associated with greater hip and knee power; less ankle dorsiflexion and hip flexion at initial contact, and less ankle and knee range of motion during stance, compared to shod running, at all speeds. Barefoot stride length was shortened, and cadence increased compared to shod during jogging and running but not sprinting. For GMFCS level I only, barefoot running involved a higher incidence of forefoot strike, greater ankle power generation and less hip range of motion during stance. SIGNIFICANCE: Running barefoot may facilitate running performance by increasing power generation at the ankle in children with CP, GMFCS level I. Higher barefoot loading rates may have implications for performance and injury.

The role of collisional ionization in heavy ion acceleration by high intensity laser pulses.

We present here simulation results of the laser-driven acceleration of gold ions using the EPOCH code. Recently, an experiment reported the acceleration of gold ions up to 7 MeV/nucleon with a strong dependency of the charge-state distribution on target thickness and the detection of the highest charge states [Formula: see text]. Our simulations using a developmental branch of EPOCH (4.18-Ionization) show that collisional ionization is the most important cause of charge states beyond Z = 51 up to He-like Au.

Enhanced inhibition of Pseudomonas aeruginosa virulence factor production and biofilm development by sublethal concentrations of eugenol and phenyllactic acid.

Biofilm development in Pseudomonas aeruginosa is regulated by its quorum sensing (QS) systems. It has three major QS systems: LasI/R, RhlI/R and PQS/MvfR. Previous studies showed that phenyllactic acid (PLA) binds to RhlR and PqsR and inhibits the Rhl and PQS QS; and eugenol at sublethal concentration inhibits Las and PQS QS systems. Here, we have demonstrated that a combination of sublethal doses of eugenol and PLA enhanced the inhibition of the QS mediated production of the virulence factors and biofilm development of this pathogen. A combination of 50 µmol l-1 eugenol and 0·3 mmol l-1 PLA significantly inhibited the pyocyanin production, protease activity, swarming motility and cytotoxic activities of P. aeruginosa strain PAO1, whereas eugenol and PLA when added individually to PAO1 cultures were less effective in inhibiting its virulence factor expression. Biofilm formation of PAO1 was reduced by 32, 19 and 87% on glass surfaces; and 54, 49 and 93% on catheter surfaces when treated using 50 µmol l-1 eugenol or 0·3 mmol l-1 PLA and their combinations, respectively. The in vitro finding in the reduction of biofilm development was further validated in vivo using a catheter associated medaka fish biofilm model. Our results indicate that a combination of QS inhibitors targeting different QS pathways should be selected while designing therapeutic molecules to achieve maximum QS mediated biofilm inhibition and clinical outcome against P. aeruginosa.

Associations with sub-optimal clinic attendance and reasons for missed appointments among heterosexual women and men living with HIV in London.

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.