Quantification and purification of isotopic contamination at the ReAccelerator of the Facility for Rare Isotope Beams.

At the ReAccelerator within the Facility for Rare Isotope Beams, a combination of an interchangeable aluminum foil and a silicon detector was developed to quantify isobaric contamination in rare isotope beams. The device is simple to operate and is now used routinely. In this article, we describe the system and show an application of the device to determine the level of contamination of an Si-32 rare isotope beam by stable S-32. In addition, we describe how the new diagnostic device helped confirm an enhancement of the beam purity prior to beam delivery to experiments.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

BACKGROUND: Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. METHODS: Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. RESULTS: At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. CONCLUSION: Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

HYSTEROSCOPIC MYOMECTOMY.

Leiomyomas are the most common pelvic tumors. Submucosal fibroids are a common cause of abnormal bleeding and infertility. Hysteroscopic myomectomy is the definitive management of symptomatic submucosal fibroids, with high efficacy and safety. Several techniques have been introduced over time and will be covered in depth in this manuscript. Advances in optics, fluid management, electrosurgery, smaller diameter scopes, and tissue removal systems, along with improved training have contributed to improving the safety and efficiency of hysteroscopic myomectomy.

Hysteroscopic Myomectomy.

Hysteroscopic myomectomy is the treatment of choice for symptomatic submucosal myomas, with excellent success rate and low complication rate.

Outcomes of laparoscopic management of chronic pelvic pain and endometriosis.

This study was designed to determine the rates of reoperation following laparoscopic management of endometriosis, with additional aims to examine long-term fertility and quality of life outcomes. This is a retrospective study and a prospective questionnaire of subjects who underwent laparoscopic surgery for pelvic pain and/or endometriosis from 2010 to 2015. The rate of reoperation was 8.60%. Following surgery, 83.3% of previously infertile subjects with endometriosis attempted to conceive with an 80.0% success rate. Subjects had significant improvement in each quality of life measurement and most sexual function indices analysed.Impact StatementWhat is already known on this subject? Endometriosis is estimated to affect around 35-50% of women experiencing chronic pelvic pain and/or infertility. Surgical management of endometriosis is recommended for patients who desire fertility, are afflicted by a more severe form of endometriosis, or have had persistent or recurrent pain in spite of medical management.What the results of this study add? The overall rate of reoperation for subjects was low at 8.6%. The majority of infertile patients were able to conceive following surgery.What the implications are of these findings for clinical practice and/or further research? Laparoscopic management of endometriosis is an effective management tool with low rates of reoperation and high efficacy in treating infertility caused by endometriosis.

HIV prevalence and HIV clinical outcomes of transgender and gender-diverse people in England.

OBJECTIVES: We provide the first estimate of HIV prevalence among trans and gender-diverse people living in England and compare outcomes of people living with HIV according to gender identity. METHODS: We analysed a comprehensive national HIV cohort and a nationally representative self-reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two-step question co-designed with community members and civil society. Responses were validated by clinic follow-up and/or self-report. Population estimates were obtained from national government offices. RESULTS: In 2017, HIV prevalence among trans and gender-diverse people was estimated at 0.46-4.78 per 1000, compared with 1.7 (95% credible interval: 1.6-1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender-diverse. Compared with cisgender people, trans and gender-diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self-care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups. CONCLUSIONS: HIV prevalence among trans and gender-diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender-diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people.

Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial.

BACKGROUND: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation. METHODS: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue. DISCUSSION: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Coronavirus disease 2019 pandemic: staged management of surgical services for gynecology and obstetrics.

The coronavirus disease 2019 pandemic warrants an unprecedented global healthcare response requiring maintenance of existing hospital-based services while simultaneously preparing for high-acuity care for infected and sick individuals. Hospitals must protect patients and the diverse healthcare workforce by conserving personal protective equipment and redeployment of facility resources. While each hospital or health system must evaluate their own capabilities and surge capacity, we present principles of management of surgical services during a health emergency and provide specific guidance to help with decision making. We review the limited evidence from past hospital and community responses to various health emergencies and focus on systematic methods for adjusting surgical services to create capacity, addressing the specific risks of coronavirus disease 2019. Successful strategies for tiered reduction of surgical cases involve multidisciplinary engagement of the entire healthcare system and use of a structured risk-assessment categorization scheme that can be applied across the institution. Our institution developed and operationalized this approach over 3 working days, indicating that immediate implementation is feasible in response to an unforeseen healthcare emergency.

Towards elimination of HIV transmission, AIDS and HIV-related deaths in the UK.

OBJECTIVES: Our objective was to present recent trends in the UK HIV epidemic (2007-2016) and the public health response. METHODS: HIV diagnoses and clinical markers were extracted from the HIV and AIDS Reporting System; HIV testing data in sexual health services (SHS) were taken from GUMCAD STI Surveillance System. HIV data were modelled to estimate the incidence in men who have sex with men (MSM) and post-migration HIV acquisition in heterosexuals. Office for National Statistics (ONS) data enabled mortality rates to be calculated. RESULTS: New HIV diagnoses have declined in heterosexuals as a result of decreasing numbers of migrants from high HIV prevalence countries entering the UK. Among MSM, the number of HIV diagnoses fell from 3570 in 2015 to 2810 in 2016 (and from 1554 to 1096 in London). Preceding the decline in HIV diagnoses, modelled estimates indicate that transmission began to fall in 2012, from 2800 [credible interval (CrI) 2300-3200] to 1700 (CrI 900-2700) in 2016. The crude mortality rate among people promptly diagnosed with HIV infection was comparable to that in the general population (1.22 vs. 1.39 per 1000 aged 15-59 years, respectively). The number of MSM tested for HIV at SHS increased annually; 28% of MSM who were tested in 2016 had been tested in the preceding year. In 2016, 76% of people started antiretroviral therapy within 90 days of diagnosis (33% in 2007). CONCLUSIONS: The dual successes of the HIV transmission decline in MSM and reduced mortality are attributable to frequent HIV testing and prompt treatment (combination prevention). Progress towards the elimination of HIV transmission, AIDS and HIV-related deaths could be achieved if combination prevention, including pre-exposure prophylaxis, is replicated for all populations.

Total Laparoscopic Hysterectomy Under Regional Anesthesia.

BACKGROUND: Laparoscopic hysterectomies comprise a large proportion of all hysterectomies in the United States. Procedures completed under regional anesthesia pose a number of benefits to patients, but laparoscopic hysterectomies traditionally have been performed under general anesthesia. We describe a case of total laparoscopic hysterectomy under epidural anesthesia with the patient fully awake. CASE: A 51-year-old woman with abnormal uterine bleeding underwent an uncomplicated total laparoscopic hysterectomy, bilateral salpingectomy, and excision of endometriosis. The procedure was completed under epidural anesthesia without intravenous sedation or systemic narcotics. Pneumoperitoneum with a pressure of 12 mm Hg and Trendelenburg to 15° allowed for adequate visualization. Anesthesia was achieved with midthoracic and low lumbar epidural catheters. Bilevel positive airway pressure was used for augmentation of respiratory function. CONCLUSION: With a committed patient, adequate planning, and knowledge of the potential intraoperative complications, regional anesthesia is an option for select women undergoing laparoscopic hysterectomy.

Improving patient experiences of mental health inpatient care: a randomised controlled trial.

BACKGROUND: Poorer patient views of mental health inpatient treatment predict both further admissions and, for those admitted involuntarily, longer admissions. As advocated in the UK Francis report, we investigated the hypothesis that improving staff training improves patients' views of ward care. METHOD: Cluster randomised trial with stepped wedge design in 16 acute mental health wards randomised (using the ralloc procedure in Stata) by an independent statistician in three waves to staff training. A psychologist trained ward staff on evidence-based group interventions and then supported their introduction to each ward. The main outcome was blind self-report of perceptions of care (VOICE) before or up to 2 years after staff training between November 2008 and January 2013. RESULTS: In total, 1108 inpatients took part (616 admitted involuntarily under the English Mental Health Act). On average 51.6 staff training sessions were provided per ward. Involuntary patient's perceptions of, and satisfaction with, mental health wards improved after staff training (N582, standardised effect -0·35, 95% CI -0·57 to -0·12, p = 0·002; interaction p value 0·006) but no benefit to those admitted voluntarily (N469, -0.01, 95% CI -0.23 to 0.22, p = 0.955) and no strong evidence of an overall effect (N1058, standardised effect -0.18 s.d., 95% CI -0.38 to 0.01, p = 0.062). The training costs around £10 per patient per week. Resource allocation changed towards patient perceived meaningful contacts by an average of £12 (95% CI -£76 to £98, p = 0.774). CONCLUSION: Staff training improved the perceptions of the therapeutic environment in those least likely to want an inpatient admission, those formally detained. This change might enhance future engagement with all mental health services and prevent the more costly admissions.

Sorafenib for the Treatment of Advanced Hepatocellular Cancer - a UK Audit.

AIMS: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials. MATERIALS AND METHODS: Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan-Meier method. RESULTS: Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17-89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin-bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n=109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients. CONCLUSION: For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment.

Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian Function and Fertility Preservation.

Survivors of pelvic cancer treatment live with the ramifications of pelvic radiation for many years after their cure. Several options are available to preserve ovarian function and fertility in reproductive age women undergoing pelvic radiation. Laparoscopic ovarian transposition is an under-utilized, yet fairly simple surgical procedure to relocate the ovaries away from the radiation field. Although randomized-controlled trials on the outcomes of ovarian transposition are scarce, there is a growing body of evidence on the risks and benefits of this procedure, in terms of prevention of premature ovarian failure, and potentially preserving fertility. In this review, we summarize the available data on the indications, patient selection and outcomes of ovarian transposition, as well as illustrate the technique of the procedure.

Domoic Acid Poisoning as a Possible Cause of Seasonal Cetacean Mass Stranding Events in Tasmania, Australia.

The periodic trend to cetacean mass stranding events in the Australian island state of Tasmania remains unexplained. This article introduces the hypothesis that domoic acid poisoning may be a causative agent in these events. The hypothesis arises from the previously evidenced role of aeolian dust as a vector of iron input to the Southern Ocean; the role of iron enrichment in Pseudo-nitzschia bloom proliferation and domoic acid production; and importantly, the characteristic toxicosis of domoic acid poisoning in mammalian subjects leading to spatial navigation deficits. As a pre-requisite for quantitative evaluation, the plausibility of this hypothesis was considered through correlation analyses between historical monthly stranding event numbers, mean monthly chlorophyll concentration and average monthly atmospheric dust loading. Correlation of these variables, which under the domoic acid stranding scenario would be linked, revealed strong agreement (r = 0.80-0.87). We therefore advocate implementation of strategic quantitative investigation of the role of domoic acid in Tasmanian cetacean mass stranding events.

Taking stock: UK national antidote availability increasing, but further improvements are required.

BACKGROUND: A 2010/2011 audit of the Royal College of Emergency Medicine (RCEM) National Poisons Information Service (NPIS) UK guidelines on antidote availability demonstrated variable stocking of antidotes for the management of poisoned patients; the guidelines were updated and republished in 2013. AIM: To assess if antidote stocking has improved since the 2010/2011 audit and introduction of the 2013 guidelines. METHODS: Questionnaires were sent to Chief Pharmacists at all 215 acute hospitals in England, Wales and Northern Ireland in October 2014. Data were collected on the timing of availability (category A antidotes should be available immediately, category B within 1 h and category C can be held supraregionally) and stock levels. RESULTS: 169 (78.6%) responses were received. Atropine, calcium gluconate and flumazenil (category A) were the only antidotes available in all hospitals within the recommended time and stock levels. Forty-one (24.3%) hospitals held every category A antidote; this increased to 81 (47.9%) for those holding at least one cyanide antidote and all other category A antidotes. The proportion of hospitals stocking category A/B antidotes within the recommended time increased for 20 (90.9%) category A/B antidotes. Fomepizole (category B) availability increased to 62.1% of hospitals from 11.4% in 2010/2011. Other than penicillamine (63.3% hospitals), there was poor availability (2.4%-36.1%) of category C antidotes. CONCLUSIONS: Availability of category A and B antidotes has improved since the 2010/2011 audit and 2013 guidelines. However, there remains significant variability particularly for category C antidotes. More work is required to ensure that those treating poisoned patients have timely access to antidotes focusing particularly on category C antidotes.

Derived neutrophil lymphocyte ratio may predict benefit from cisplatin in the advanced biliary cancer: the ABC-02 and BT-22 studies.

BACKGROUND: The superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone in patients with advanced biliary tract cancer (ABC) has been demonstrated in two randomised trials; ABC02 and the Biliary Tract (BT) 22 study. We used a combined dataset from these two trials to investigate the derived neutrophil-to-lymphocyte ratio (dNLR), which is thought to be a prognostic factor associated with clinical outcomes in several solid tumours, including ABC. METHODS: White blood cell (WBC) and absolute neutrophil count (ANC) were available for 379 of 410 patients from ABC-02 and all 83 patients in BT-22. The dNLR was calculated as ANC/(WBC-ANC), as previously specified. We examined the association between dNLR and overall survival (OS) and progression-free survival (PFS), as well as comparing the treatment effect in two patient groups defined by their dNLR level. A high dNLR was defined as ≥3.0, which was approximately the upper tertile value. RESULTS: A total of 462 individual patient records were analysed, 328 with baseline dNLR <3 and 134 with dNLR ≥3. There were 443 deaths in the cohort, and all surviving patients had a dNLR <3. There was strong evidence that dNLR was closely associated with both OS [hazard ratio (HR), 1.62; 95% confidence interval (CI) 1.32-2.01] and PFS (HR, 1.40; 95% CI 1.13-1.72). There was limited evidence (P = 0.10) of a differential effect of CisGem on OS between the two dNLR groups, but this was clearest in the ABC-02 dataset (P = 0.06). There was good evidence (P = 0.008) of an association between low baseline dNLR and long-term survival on a CisGem regimen. There was also good evidence of an association between ECOG performance status (split at 0 and 1 versus 2) on both OS (P < 0.001) and PFS (P = 0.01), but no evidence of a differential treatment effect, with both groups receiving benefit from the addition of cisplatin. CONCLUSIONS: These data confirm that high dNLR is associated with worse OS and PFS, and suggests it may also be predictive of benefit for the addition of cisplatin to gemcitabine in European patients with ABC. Incorporating dNLR into the clinical context may better inform prognosis and chemotherapy decisions in ABC patients.