Diagnosis and management of pneumonitis following chemoradiotherapy and immunotherapy in stage III non-small cell lung cancer.

BACKGROUND: In inoperable stage III NSCLC, the standard of care is chemoradiotherapy and adjuvant durvalumab (IO) for 12 months. Pneumonitis is the commonest toxicity leading to discontinuation of IO. A failure to distinguish between expected radiation-induced changes, IO pneumonitis and infection can lead to unnecessary durvalumab discontinuation. We investigated the use of a structured multidisciplinary review of CT-scans, radiation dose distributions and clinical symptoms for the diagnosis of IO pneumonitis. METHODS: A retrospective study was conducted at an academic medical center for patients treated for stage III NSCLC with chemoradiotherapy and adjuvant durvalumab between 2018 and 2021. An experienced thoracic radiologist reviewed baseline and follow-up chest CT-scans, systematically scored radiological features suspected for pneumonitis using a published classification system (Veiga C, Radioth Oncol 2018), and had access to screenshots of radiation dose distributions. Next, two experienced thoracic oncologists reviewed each patients' case record, CT-scans and radiation fields. A final consensus diagnosis incorporating views of expert clinicians and the radiologist was made. RESULTS: Among the 45 included patients, 14/45 (31.1%) had a pneumonitis scored in patient records and durvalumab was discontinued in 11/45 cases (24.4%). Review by the radiologist led to a diagnosis of immune-related pneumonitis only in 6/45 patients (13.3%). Review by pulmonary oncologists led to a diagnosis of immune-related pneumonitis in only 4/45 patients (8.9%). In addition a suspicion of an immune-related pneumonitis was rejected in 3 separate patients (6.7%), after the thoracic oncologists had reviewed the patients' radiation fields. CONCLUSIONS: In patients treated using the PACIFIC regimen, multidisciplinary assessment of CT-scans, radiation doses and patient symptoms, resulted in fewer diagnoses of immune-related pneumonitis (8.9%). Our study underscores the challenges in accurately diagnosing either IO-related or radiation pneumonitis in patients undergoing adjuvant immunotherapy after chemoradiotherapy and highlights the need for multidisciplinary review in order to avoid inappropriate cessation of adjuvant IO.

The sexuality of women with cervical cancer undergoing definitive radiotherapy in Ghana.

INTRODUCTION: The purpose of this study was to assess the sexuality of cervical cancer patients undergoing radiotherapy at a major cancer treatment center in Ghana. This is an area of interest as globally; cervical cancer kills approximately 342,000 people per annum with an estimated number of 604,000 new cases in 2020. Acknowledging the World Health Organization's definition of sexual health as a state of physical, mental and social well-being in relation to sexuality, this paper sheds light on how these dimensions affect the quality of life of cervical cancer patients. METHODS: This was a longitudinal study, which assessed the impact of radiotherapy on the sexuality of both premenopausal and postmenopausal cervical cancer patients presenting for primary treatment with chemoradiation from April to July, 2021 at a major cancer treatment centre in Ghana. The Female Sexual Function Index and Body Image Scale questionnaires were respectively used to evaluate the sexual functions scores among the cervical cancer patients, and to assess the impact of the treatment on their body image. MATLAB software was used for data analysis. RESULTS: Most of the cervical cancer patients sampled were postmenopausal (57 %). About 79 % premenopausal and 96 % postmenopausal cervical cancer patients were sexually inactive during radiotherapy (day 15). Also, 48 % premenopausal and 24 % postmenopausal patients were very dissatisfied with their bodies at the onset of treatment. The frequency of orgasm in cervical cancer patients declined after treatment causing a deterioration in their sexual function. The patients' sexuality was influenced by age and menopausal status. The decreased sexual desire of the patients resulted in emotional distancing from their partners, which invariably induced changes in their partners' level of sexual interest. This study established significant differences between premenopausal and postmenopausal cervical cancer patients who were generally very dissatisfied with their sexual relationships with their partners on day 1 (p = 0.02) and on day 15 (p = 0.00) of treatment. CONCLUSION: The majority of patients who presented for treatment for cervical cancer in this study were postmenopausal. Their interest in sexual activity was more influenced by their menopausal status than their antineoplastic treatment. This study indicates that cervical cancer patients are more likely to develop sexual health problems which could substantially worsen over the course of their treatment and beyond. IMPLICATION FOR PRACTICE: The study will contribute within the oncology team by assisting personnel in putting in place measures that will guide the treatment of cervical cancer patients and improve quality of care.

The effects of simulated hydropower turbine rapid decompression on two Neotropical fish species.

Barotrauma is a major cause of injury and mortality of fish as they pass through hydropower turbines. Current understanding of hydropower related barotrauma is biased towards northern temperate and southern subtropical species with single chambered swim bladders, specifically North American and Australian species, respectively. Today, unprecedented hydropower development is taking place in Neotropical regions where many species have complex multi-chambered swim bladder architecture. This study investigated barotrauma in two dual-chambered physostomous Neotropical fish (pacu, Piaractus mesopotamicus, and piracanjuba, Brycon orbignyanus) exposed to rapid (< 1 s) decompression at different Ratios of Pressure Change (RPC), using a hypo-hyperbaric chamber. The incidence and intensity (percentage surface area of organ affected) of injury and physiological and behavioural response (hereafter just response) of each species immediately after decompression was assessed. Twenty-two injury types (e.g. gill haemorrhage and exophthalmia) and eight response categories (e.g. rising to the surface and loss of orientation) were identified and the influence of: 1) species, 2) RPC, and 3) swim bladder rupture on each was quantified. There was considerable interspecific difference with emboli type injuries occurring more frequently in piracanjuba, but injury intensity tending to be higher in pacu. Both swim bladder chambers tended to rupture in piracanjuba but only the anterior chamber in pacu. RPC was positively correlated with response, incidence and intensity of several injury types for both species with some injuries occurring at very low RPC (e.g. 50 % probability of swim bladder rupture at 2.2 and 1.75 for piracanjuba and pacu, respectively). Multiple responses (e.g. loss of orientation) and injuries (e.g. eye haemorrhage) were correlated with swim bladder rupture suggesting gas venting into the body cavity likely causes secondary injury. When directly comparing our results with those available in the published literature, both pacu and piracanjuba appear to be more susceptible to barotrauma than previously studied subtropical and temperate species.

Systematic review of the effectiveness of remifentanil in term breech pregnancies undergoing external cephalic version.

BACKGROUND: External cephalic version (ECV) is a moderately painful procedure used to turn a fetus from a non-vertex to cephalic position. This systematic review and meta-analysis compared intravenous remifentanil with other analgesia or no analgesia or placebo on the success rate and associated pain of ECV. METHODS: Systematic searches for randomised controlled trials using remifentanil during ECV for non-cephalic term singleton pregnancies were conducted in EMBASE, MEDLINE and the Cochrane Library to October 2021. The primary outcomes were successful ECV and maternal pain; secondary outcomes included mode of delivery and adverse effects. The Cochrane Risk of Bias tool was used and meta-analysis undertaken if there were ≥2 comparable studies. RESULTS: Four trials were identified, three placebo-controlled and one vs no analgesia, totalling 482 participants. Comparisons against nitrous oxide or neuraxial anaesthesia were not analysed. Two studies had a low overall risk of bias, and two had some concern for bias. Remifentanil compared with placebo increased the success of ECV by 43% (risk ratio [RR] 1.43; 95% confidence interval [CI] 1.14 to 1.78). Pain scores (0-10) were lower (mean difference -1.97; 95% CI -2.49 to -1.46) whilst there was no impact on caesarean delivery rate (RR 0.97; 95% CI 0.81 to 1.17). Adverse events were rare, with fetal bradycardia observed less often with remifentanil than placebo. CONCLUSIONS: Remifentanil increases the procedural success of ECV and reduces pain compared with placebo. Trials were at low risk of bias and contained a sufficient number of participants to have reasonable confidence in this finding.

Reasons for missed opportunities to screen and test for TB in healthcare facilities.

Missed opportunities for TB screening and/or passive testing in clinics continues to contribute to the number of missed cases. To understand reasons for these missed opportunities, we conducted focus group discussions with clinic-based nurses. Nurses described low indices of suspicion, prioritization of seemingly more urgent ailments and clinic operational challenges as barriers to TB screening and testing. To improve TB screening and testing in clinics, standard patients should be used to identify real-time factors that impact nurses' clinical decision-making and engage in real-time feedback and discussion with nurses to help optimize opportunities for TB screening and testing.

Les occasions manquées de dépistage de la TB et/ou de tests passifs dans les cliniques continuent de contribuer au nombre de cas manqués. Pour comprendre les raisons de ces occasions manquées, nous avons organisé des discussions de groupe avec des infirmières travaillant dans des cliniques. Les infirmières ont décrit les faibles indices de suspicion, la priorité accordée à des affections apparemment plus urgentes et les défis opérationnels des cliniques comme des obstacles au dépistage de la TB. Pour améliorer le dépistage et le test de la TB dans les cliniques, il faudrait utiliser des patients standard pour identifier les facteurs en temps réel qui influent sur la prise de décision clinique des infirmières et engager une rétroaction et une discussion en temps réel avec les infirmières pour aider à optimiser les occasions de dépistage et de test de la TB.

Causes of loss to follow-up from drug-resistant TB treatment in Khayelitsha, South Africa.

Patients initiated on drug-resistant TB(DR-TB) treatment in 2019 in Khayelitsha, South Africa, with a loss to follow-up outcome were evaluated to better understand reasons for loss to follow-up and to determine if any had returned to care. Of a total of 187 patients, 28 (15%) were lost to follow-up (LTFU), 24 (86%) of whom were traced: 20/24 (83%) were found when they re-presented to facilities and 8/28 (29%) were linked back to DR-TB care. People with DR-TB continue to seek care even after being LTFU; thus better coordination between different components of the healthcare system are required to re-engage with these patients. Interventions to mitigate the socio-economic challenges of people on DR-TB treatment are needed. Many people who were LTFU and symptomatic were willing to re-engage with DR-TB care, which highlights the importance of for compassionate interventions to welcome them back.

Les patients placés sous traitement pour TB pharmacorésistante (DR-TB) en 2019 à Khayelitsha, Afrique du Sud, et ayant été perdus de vue ont été évalués afin de mieux comprendre les raisons de la perte de vue et de déterminer si certains étaient de nouveau suivis. Sur 187 patients, 28 (15%) ont été perdus de vue, dont 24 (86%) ont été retrouvés : 20/24 (83%) ont été retrouvés lorsqu'ils se sont de nouveau présentés en consultation et 8/28 (29%) ont été réinsérés dans le parcours de soins de la DR-TB. Les patients atteints de DR-TB sont toujours en demande de soins, même après avoir été perdus de vue. Ainsi, une meilleure coordination entre les différentes composantes du système de santé est nécessaire afin de rétablir le lien avec ces patients. Des interventions visant à atténuer les problèmes socio-économiques des patients sous traitement pour DR-TB sont nécessaires. De nombreux patients symptomatiques ayant été perdus de vue étaient enclins à reprendre leur traitement de la DR-TB. Il est donc important de mettre en place des programmes compassionnels afin de les réinsérer dans le parcours de soins.

Early mortality during rifampicin-resistant TB treatment.

BACKGROUND: Data suggest that treatment with newer TB drugs (linezolid [LZD], bedaquiline [BDQ] and delamanid [DLM]), used in Khayelitsha, South Africa, since 2012, reduces mortality due to rifampicin-resistant TB (RR-TB).METHODS: This was a retrospective cohort study to assess 6-month mortality among RR-TB patients diagnosed between 2008 and 2019.RESULTS: By 6 months, 236/2,008 (12%) patients died; 12% (78/651) among those diagnosed in 2008-2011, and respectively 8% (49/619) and 15% (109/738) with and without LZD/BDQ/DLM in 2012-2019. Multivariable analysis showed a small, non-significant mortality reduction with LZD/BDQ/DLM use compared to the 2008-2011 period (aOR 0.79, 95% CI 0.5-1.2). Inpatient treatment initiation (aOR 3.2, 95% CI 2.4-4.4), fluoroquinolone (FQ) resistance (aOR 2.7, 95% CI 1.8-4.2) and female sex (aOR 1.5, 95% CI 1.1-2.0) were also associated with mortality. When restricted to 2012-2019, use of LZD/BDQ/DLM was associated with lower mortality (aOR 0.58, 95% CI 0.39-0.87).CONCLUSIONS: While LZD/BDQ/DLM reduced 6-month mortality between 2012 and 2019, there was no significant effect overall. These findings may be due to initially restricted LZD/BDQ/DLM use for those with high-level resistance or treatment failure. Additional contributors include increased treatment initiation among individuals who would have otherwise died before treatment due to universal drug susceptibility testing from 2012, an effect that also likely contributed to higher mortality among females (survival through to care-seeking).

Managing an adult CF population in the COVID-19 pandemic-1 year on.

BACKGROUND: The advent of the COVID-19 pandemic in 2020 required an alteration in the routine care of people with CF (pwCF), deemed to be extremely vulnerable. AIM: We wished to report the alterations in clinical practice, including the introduction of remote video-assisted clinics, made to manage the adult pwCF attending our large centre. METHODS: We studied clinical records over a period of 2 years (March 2019 to February 2021) by comparing 19th March to 20th February (Y1) with 20th March to 21st February (Y2). RESULTS: We have shown out of hospital Multi Disciplinary Team (MDT) support increased and a greater proportion of IV therapy was administered at home. The VAC model of care increased clinical activity while reducing clinic non-attendance rates, suggesting more individuals engage with their carers. CONCLUSIONS: This new model of care has allowed greater engagement with pwCF.

Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions.

Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease.

Morbidity and extent of surgical resection of carcinoid tumors after endobronchial treatment.

OBJECTIVES: This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity. MATERIAL AND METHODS: Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups. RESULTS: A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT). CONCLUSION: EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.

Uterine artery embolisation or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: a cost-utility analysis of the FEMME trial.

OBJECTIVES: To assess the cost-effectiveness of uterine artery embolisation (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. DESIGN: Economic evaluation alongside the FEMME randomised controlled trial. SETTING: 29 UK hospitals. POPULATION: Premenopausal women who had symptomatic uterine fibroids amenable to UAE or myomectomy wishing to avoid hysterectomy. 254 women were randomised to UAE (127) and myomectomy (127). METHODS: A within-trial cost-utility analysis was conducted from the perspective of the UK NHS. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) measured using the EuroQoL EQ-5D-3L, combined with costs to estimate cost-effectiveness over 2 and 4 years of follow-up. RESULTS: Over a 2-year time horizon, UAE was associated with higher mean costs (difference £645; 95% CI -1381 to 2580) and lower QALYs (difference -0.09; 95% CI -0.11 to -0.04) when compared with myomectomy. Similar results were observed over the 4-year time horizon. Thus, UAE was dominated by myomectomy. Results of the sensitivity analyses were consistent with the base case results for both years. Over 2 years, UAE was associated with higher costs (difference £456; 95% CI -1823 to 3164) and lower QALYs (difference -0.06; 95% CI -0.11 to -0.02). CONCLUSIONS: Myomectomy is a cost-effective option for the treatment of uterine fibroids. The differences in costs and QALYs are small. Women should be fully informed and have the option to choose between the two procedures. TWEETABLE ABSTRACT: Fully informed women with uterine fibroids should have a choice between uterine artery embolisation or myomectomy.

Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy.

Premature ovarian insufficiency (POI) - the loss of ovarian function before the age of 40 years, a decade before natural menopause - is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women's decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI.

Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC).

BACKGROUND: Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. There is an unmet need for new medical treatment options for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that creates an environment favouring the formation and survival of endometriosis lesions. We have generated powerful preclinical proof-of-concept data to show that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), a non-hormonal compound previously used to treat rare metabolic disorders in children. We plan a single-arm, open-label, single site exploratory clinical trial to inform the design of a future randomised controlled trial (RCT) to determine the efficacy of DCA for the treatment of endometriosis-associated pain. METHODS: We will recruit 30 women with endometriosis-associated pain over a 6-month period. All participants will receive approximately 6.25 mg/kg oral DCA capsules twice daily for 6 weeks, with a dose increase to approximately 12.5 mg/kg twice daily for a further 6 weeks if their pain has not been adequately controlled on this dose regime and side-effects are acceptable. If pain is adequately controlled with minimal side-effects, the lower dose will be continued for a further 6 weeks. The primary objective is to determine whether it is possible to achieve acceptable recruitment and retention rates within the defined exclusion and inclusion criteria. Secondary objectives are to determine the acceptability of the trial to participants, including the proposed methods of recruitment, treatment, follow-up frequency and number of questionnaires. The recruitment rate will be determined by the proportion of patients recruited from the pool of eligible women. The retention rate will be determined by the proportion of participants who attended the final trial visit. DISCUSSION: This is a feasibility study to explore effectiveness and acceptability of the proposed field methodology (recruitment, retention, study processes and compliance with treatment). The results will be used to inform the design of a future RCT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04046081 Registered 6 August 2019.

Practitioner review: health anxiety in children and young people in the context of the COVID-19 pandemic.

Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.

Crop production in the USA is frequently limited by a lack of pollinators.

Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.