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Kirsten Kiers, Josef Kröll, Gerald Mitterbauer, Johannes Scherr,
Published: 16 September 2021
by BMJ
BMJ Open Sport & Exercise Medicine, Volume 7; https://doi.org/10.1136/bmjsem-2021-001111

Abstract:
Objectives (1) To update experts’ priorities of perceived key injury risk factors in alpine ski racing based on a framework and list derived 10 years ago, (2) to identify additionally emerging risk factors since then and (3) to compile a list with countermeasure suggestions. Methods A sample of 532 expert stakeholders (athletes, coaches, team medical staff, Ski Racing Suppliers (SRS) and International Ski Federation (FIS) representatives) from the World Cup (WC), European Cup (EC) and FIS-race level participated in a cross-sectional online survey. Experts were asked to name those risk factors with the highest believed impact on injury risk and rank them according to their current priority from a predefined list. In addition, experts were encouraged to name additional (not listed) risk factors and to suggest countermeasures. Results Regardless of stakeholder role and competition level, snow-related factors appeared to have the highest perceived priority. However, WC athletes’ and coaches’ perceptions were also related to equipment, while at the EC and FIS-race level fatigue and physical fitness-related factors were considered important. Athletes’ perceptions were largely in agreement with SRS (ie, snow-related and equipment-related factors). At the same time, while coaches, team medical staff and FIS representatives additionally emphasised fatigue and physical fitness-related factors. Conclusion Experts’ perceptions on key injury risk factors in alpine ski racing depend on the stakeholder role and differ between the competition levels. Thus, to develop effective prevention measures and to successfully implement them, all relevant stakeholders should be given a voice, and prevention efforts should be targeted to the specific level.
, Monica Siaulys, Rachel Riera, Ana Luiza Cabrera Martimbianco, Rafael Leite Pacheco, Carolina De Oliveira Cruz Latorraca, Mariana Widmer, Ana Pilar Betran
Published: 16 September 2021
by BMJ
Abstract:
Objectives Assess the effects of different routes of prophylactic oxytocin administration for preventing blood loss at caesarean section (CS). Design Systematic review and meta-analysis. Methods Medline, EMBASE, CINAHL, Cochrane Library, BVS, SciELO and Global Index Medicus were searched through 24 May 2020 for randomised controlled trials (RCTs) comparing different routes of prophylactic oxytocin administration during CS. Study selection, data extraction and quality assessment were conducted by two investigators independently. We pooled results in fixed effects meta-analyses and calculated average risk ratio (RR), mean difference (MD) and 95% CI. We used GRADE to assess the overall quality of evidence for each outcome. Results Three trials (180 women) were included in the review. All studies compared intramyometrial (IMY) versus intravenous oxytocin in women having prelabour CS. IMY compared with intravenous oxytocin administration may result in little or no difference in the incidence of postpartum haemorrhage (RR 0.14, 95% CI 0.01 to 2.70; N=100 participants; 1 RCT), hypotension (RR 1.00, 95% CI 0.29 to 3.45; N=40; 1 RCT), headache (RR 3.00, 95% CI 0.13 to 69.52; N=40; 1 RCT) or facial flushing (RR 0.50, 95% CI 0.05 to 5.08; N=40; 1 RCT); IMY oxytocin may reduce nausea/vomiting (RR 0.13, 95% CI 0.02 to 0.69; N=140; 2 RCTs). We are very uncertain about the effect IMY versus intravenous oxytocin on the need for additional uterotonics (RR 0.82; 95% CI 0.25 to 2.69; N=140; 2 RCTs). IMY oxytocin may reduce blood loss slightly (MD −57.40 mL, 95% CI −101.71 to −13.09; N=40; 1 RCT). Conclusions There is limited, low to very low certainty evidence on the effects of IMY versus intravenous oxytocin at CS for preventing blood loss. The evidence is insufficient to support choosing one route over another. More trials, including studies that assess intramuscular oxytocin administration, are needed on this relevant question. PROSPERO registration number CRD42020186797.
Kamlesh Kothari, , Aayesha Razzaque
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-245120

Abstract:
Ankylosis of the temporomandibular joint is a debilitating condition resulting in progressive trismus and facial disfigurement. Common trigger factors include paediatric mandibular trauma, middle ear infection or traumatic childbirth. Although diminishing in incidence among urban population, it is still prevalent in the underprivileged world. Substandard child safety norms, delayed presentation, lack of access to specialties like maxillofacial surgery in rural areas and absence of follow-up contribute to ankylosis. Afflictions in ankylosis are multipronged, involving aesthetic, functional, psychological and nutritional implications to name a few. The damage this pathology causes to the young mind and their morale is humongous. Although well documented, a complete presentation of cases with follow-up till oral and myofascial rehabilitation is seldom reported. This paper describes multidisciplinary management of a young female patient with temporomandibular joint ankylosis. Staged management commencing from interpositional arthroplasty until dental restoration with a 2-year follow-up is presented in this paper.
Sanjeev Yadav, Rajeev Kumar, Rakesh Kumar,
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-243530

Abstract:
Mucormycosis is a very commonly encountered disease in the sinonasal region in patients with diabetes and immunocompromised status specially in the northern part of the Indian continent. Due to its fulminant nature and involvement in the rhino-orbital-cerebral region, prognosis is poor even after extensive debridement and amphotericin-B therapy. We present a case with diagnosis of sarcoidosis being treated with systemic steroids who developed sudden-onset ptosis and left lateral rectus palsy. On radiological evaluation with MRI, a heterogenously peripherally enhancing lesion was seen in the nasopharynx suggestive of nasopharyngeal abscess. The patient was taken up for emergency surgery; a necrotic lesion with destruction of sphenoid bone, pterygoids and clivus was seen originating in the nasopharynx. The lesion on fungal staining came out to be broad aseptate hyphae suggestive of mucormycosis.
, , , Clarissa A Pilkington, Reema Syed, Syuji Takei, Diego O Viola, , , , et al.
Published: 16 September 2021
by BMJ
Abstract:
Objective To assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE). Methods We performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score; anti-dsDNA/C3/C4 levels); Week 52 SRI-6 response rate; and time to first severe flare (SELENA-SLEDAI Flare Index) over 52 weeks. Safety data were compared for all aforementioned studies along with adult LBSL02 (phase II) and BLISS-SC (phase III). Results SRI-4 response rates were similar across the paediatric and adult studies; more belimumab-treated patients achieved SRI-4 responses versus placebo (PLUTO: 52.8% vs 43.6%; BLISS-52: 57.6% vs 43.6%; BLISS-76: 43.2% vs 33.8%; BLISS-NEA: 53.8% vs 40.1%; EMBRACE: 48.7% vs 41.6%). Across all studies, SRI-4 response rates were generally greater in patients with baseline SELENA-SLEDAI scores ≥10 than in patients with baseline SELENA-SLEDAI scores ≤9. A similar proportion of belimumab-treated patients achieved SRI-6 across all studies (PLUTO: 41.2%; BLISS-52: 46.2%; BLISS-76: 33.1%; BLISS-NEA: 43.9%; EMBRACE: 37.5%). Belimumab reduced the risk of severe flare versus placebo in all studies. The incidence of adverse events was similar across all studies. Conclusions These analyses demonstrate consistent efficacy and safety of belimumab plus standard therapy across paediatric and adult patients with SLE. Trial registration numbers PLUTO (NCT01649765); BLISS-52 (NCT00424476); BLISS-76 (NCT00410384); BLISS-NEA (NCT01345253); EMBRACE (NCT01632241); BLISS-SC (NCT01484496); and LBSL02 (NCT00071487).
, Enrique Coss-Adame, Mercedes Amieva-Balmori, José Antonio Velarde-Ruiz Velasco, Paulo César Gómez-Castaños, Ricardo Flores-Rendón, Octavio Gómez-Escudero, María Celina Rodríguez-Leal, Cristina Durán-Rosas, Samanta Mayanin Pinto-Gálvez, et al.
Published: 16 September 2021
by BMJ
BMJ Open Gastroenterology, Volume 8; https://doi.org/10.1136/bmjgast-2021-000729

Abstract:
Objective A minimum of physical activity and low liquid intake are factors that have been associated with constipation. The health emergency brought on by the COVID-19 pandemic has resulted in adopting behaviour, such as sheltering-in-place (less mobility) and dietary changes, creating a scenario we believe to be an adequate model for examining the appearance of symptoms of constipation and its associated factors. Design A cross-sectional and descriptive study was conducted on an open population, applying an electronic survey (4 weeks after lockdown due to COVID-19 in Mexico) to evaluate demographic characteristics, physical activity, water and fibre intake, appearance of constipation symptoms (including stool consistency), and quality of life. Results Out of 678 subjects evaluated, 170 (25%, 95% CI: 21.7 to 28.4) developed symptoms of ‘new-onset’ constipation, with a significant decrease in the number of daily bowel movements (p<0.05) and stool consistency (p<0.05) during lockdown. Furthermore, in the ‘new-onset’ constipation population there was a higher proportion of subjects (79 (47%) of 170) who stopped exercising during the pandemic compared with the subjects who did not develop constipation symptoms (187 (37%) of 508, p=0.03, OR: 1.49, 95% CI: 1.0 to 2.1). The multivariate analysis (logistic regression) showed that female sex (p=0.001), water intake (p=0.039), and physical activity (p=0.012) were associated with ‘new-onset’ constipation. Conclusions In our study on an open population in Mexico, we found that one-fourth of the population developed ‘new-onset’ constipation symptoms during the lockdown imposed due to the COVID-19 pandemic. A reduction of physical activity and less water consumption were associated factors.
M C Sage Ishimwe, Annemarie Wentzel, Elyssa M Shoup, Nana H Osei-Tutu, Thomas Hormenu, Arielle C Patterson, Hadi Bagheri, Christopher W DuBose, Lilian S Mabundo, Joon Ha, et al.
Published: 16 September 2021
by BMJ
BMJ Open Diabetes Research & Care, Volume 9; https://doi.org/10.1136/bmjdrc-2021-002447

Abstract:
Introduction Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America. Research design and methods Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan. Results The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group. Conclusions Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ. Trial registration number NCT00001853.
, Atmakur Snigdha, N K Manjunath, Raghuram Nagarathna, Ramesh Mavathur, Amit Singh, Kalpana S R, Nagendra H R
Published: 16 September 2021
by BMJ
Abstract:
Introduction The conceptualisation of healthy ageing phenotype (HAP) and the availability of a tentative panel for HAP biomarkers raise the need to test the efficacy of potential interventions to promote health in older adults. This study protocol reports the methodology for a 24-week programme to explore the holistic influence of the yoga-based intervention on the (bio)markers of HAP. Methods and analysis The study is a two-armed, randomised waitlist controlled trial with blinded outcome assessors and multiple primary outcomes. We aim to recruit 250 subjects, aged 60–80 years from the residential communities and old age clubs in Bangalore city, India, who will undergo randomisation into intervention or control arms (1:1). The intervention will include a yoga-based programme tailored for the older adults, 1 hour per day for 6 days a week, spread for 24 weeks. Data would be collected at the baseline and post-intervention, the 24th week. The multiple primary outcomes of the study are the (bio)markers of HAP: glycated haemoglobin, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, and forced expiratory volume in 1 s for physiological and metabolic health; Digit Symbol Substitution Test, Trail Making Tests A and B for cognition; hand grip strength and gait speed for physical capability; loneliness for social well-being and WHO Quality of Life Instrument-Short Form for quality of life. The secondary outcomes include inflammatory markers, tumour necrosis factor-alpha receptor II, C reactive protein, interleukin 6 and serum Klotho levels. Analyses will be by intention-to-treat and the holistic impact of yoga on HAP will be assessed using global statistical test. Ethics and dissemination The study is approved by the Institutional Ethics Committee of Swami Vivekananda Yoga Anusandhana Samsthana University, Bangalore (ID: RES/IEC-SVYASA/143/2019). Written informed consent will be obtained from each participant prior to inclusion. Results will be available through research articles and conferences. Trial registration number CTRI/2021/02/031373.
, Alexandros Rekkas, Jelmer Alsma, Rob J C G Verdonschot, Dick T J J Koning, Marlijn J A Kamps, Tom Dormans, Robert Stassen, Sebastiaan Weijer, Klaas-Sierk Arnold, et al.
Published: 16 September 2021
by BMJ
Abstract:
Objectives Develop simple and valid models for predicting mortality and need for intensive care unit (ICU) admission in patients who present at the emergency department (ED) with suspected COVID-19. Design Retrospective. Setting Secondary care in four large Dutch hospitals. Participants Patients who presented at the ED and were admitted to hospital with suspected COVID-19. We used 5831 first-wave patients who presented between March and August 2020 for model development and 3252 second-wave patients who presented between September and December 2020 for model validation. Outcome measures We developed separate logistic regression models for in-hospital death and for need for ICU admission, both within 28 days after hospital admission. Based on prior literature, we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. We assessed model performance by the area under the receiver operating characteristic curve (AUC) and by calibration plots. Results Of 5831 first-wave patients, 629 (10.8%) died within 28 days after admission. ICU admission was fully recorded for 2633 first-wave patients in 2 hospitals, with 214 (8.1%) ICU admissions within 28 days. A simple model—COVID outcome prediction in the emergency department (COPE)—with age, respiratory rate, C reactive protein, lactate dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well calibrated and showed good discrimination for mortality in second-wave patients (AUC in four hospitals: 0.82 (95% CI 0.78 to 0.86); 0.82 (95% CI 0.74 to 0.90); 0.79 (95% CI 0.70 to 0.88); 0.83 (95% CI 0.79 to 0.86)). COPE was also able to identify patients at high risk of needing ICU admission in second-wave patients (AUC in two hospitals: 0.84 (95% CI 0.78 to 0.90); 0.81 (95% CI 0.66 to 0.95)). Conclusions COPE is a simple tool that is well able to predict mortality and need for ICU admission in patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.
Kathrin Louise Braeuninger-Weimer, Naffis Anjarwalla, Alison H McGregor, , Philip Sell, Tamar Pincus
Published: 16 September 2021
by BMJ
Abstract:
Objective This study aimed to explore the perceptions of orthopaedic clinicians about consultations for people with persistent musculoskeletal low back pain (PMLBP) in which surgery is not recommended. Surgery is not recommended for the majority of PMLBP consulting in secondary care settings. Setting Secondary care sector in the UK. Participants Semi-structured qualitative interviews were conducted with 24 orthopaedic team clinicians from 17 different hospitals in the UK and Ireland. Interviews explored clinicians’ perceptions of the challenges in consultations where surgery is not indicated. Interviews were transcribed verbatim and analysed using thematic analysis. Results Two meta-themes, Difficulties and Enablers, each consisting of several subthemes were identified. Difficulties included challenges around the choice of appropriate terminology and labels for PMLBP, managing patients’ expectations, working with mentally vulnerable patients and explaining imaging findings. Enablers included early management of expectations, use of routine imaging, triaging, access to direct referral elsewhere, including other non-surgical practitioners in the team, training to improve communication skills and understanding of psychological issues. Conclusion The findings highlight clinicians’ perceived need for concordance in messages delivered across the care pathway and training of orthopaedic clinicians to deliver effective reassurance and address patients’ needs in circumstances where surgery is not indicated.
, Janusz Jankowski, Angharad P Davies, Peter English, Ellis Friedman, Helena McKeown, Su Sethi, Mala Rao
Published: 16 September 2021
by BMJ
Abstract:
Objectives Healthcare workers have greater exposure to SARS-CoV-2 and an estimated 2.5-fold increased risk of contracting COVID-19 than the general population. We wished to explore the predictive role of basic demographics to establish a simple tool that could help risk stratify healthcare workers. Setting We undertook a review of the published literature (including multiple search strategies in MEDLINE with PubMed interface) and critically assessed early reports on preprint servers. We explored the relative risk of mortality from readily available demographics to identify the population at the highest risk. Results The published studies specifically assessing the risk of healthcare workers had limited demographics available; therefore, we explored the general population in the literature. Clinician demographics: Mortality increased with increasing age from 50 years onwards. Male sex at birth, and people of black and minority ethnicity groups had higher susceptibility to both hospitalisation and mortality. Comorbid disease. Vascular disease, renal disease, diabetes and chronic pulmonary disease further increased risk. Risk stratification tool: A risk stratification tool was compiled using a white female aged <50 years with no comorbidities as a reference. A point allocated to risk factors was associated with an approximate doubling in risk. This tool provides numerical support for healthcare workers when determining which team members should be allocated to patient facing clinical duties compared with remote supportive roles. Conclusions We generated a tool that provides a framework for objective risk stratification of doctors and healthcare professionals during the COVID-19 pandemic, without requiring disclosure of information that an individual may not wish to share with their direct line manager during the risk assessment process. This tool has been made freely available through the British Medical Association website and is widely used in the National Health Service and other external organisations.
Published: 16 September 2021
by BMJ
BMJ Sexual & Reproductive Health; https://doi.org/10.1136/bmjsrh-2021-201259

Abstract:
Background While abortion care is widely legal in Australia, access to care is often poor. Many Australians must travel long distances or interstate to access abortion care, while others face stigma when seeking care. Telehealth-at-home medical abortion is a potential solution to these challenges. In this study, we compared the experience of accessing an abortion via telehealth-at-home to accessing care in-clinic. Methods Over a 20-month period, we surveyed patients who received medical abortion services at Marie Stopes Australia via the telehealth-at-home service or in-clinic. We conducted bivariate analyses to assess differences in reported acceptability and accessibility by delivery model. Results In total, 389 patients were included in the study: 216 who received medical abortion services in-clinic and 173 through the telehealth-at-home service. Telehealth-at-home and in-clinic patients reported similarly high levels of acceptability: satisfaction with the service (82% vs 82%), provider interaction (93% vs 84%), and recommending the service to a friend (73% vs 72%). Only 1% of telehealth-at-home patients reported that they would have preferred to be in the same room as the provider. While median time between discovering the pregnancy to first contact with a clinic was similar between groups, median time from first contact to taking the first abortion medication was 7 days longer for telehealth-at-home patients versus in-clinic patients (14 days (IQR 9–21) vs 7 days (IQR 4–14); p<0.01). Conclusion The telehealth-at-home medical abortion service has the potential to address some of the challenges with provision of abortion care in Australia.
, , Jeffrey Woods, , Anita Hodge, Cathy Jones, Damien Lloyd, Vincent Rovtar, , Victoria Atkinson
Published: 16 September 2021
by BMJ
Abstract:
Introduction Incorporating patient-reported outcome measures (PROMs) into usual care in hospitals can improve safety and quality. Gaps exist in electronic PROM (ePROM) implementation recommendations, including for elective surgery. The aims are to: (1) understand barriers and enablers to ePROM implementation in hospitals and develop Australian ePROM implementation recommendations (AusPROM); (2) test the feasibility and acceptability of the Quality of Recovery 15 item short-form (QoR-15) PROM for elective surgery patients applying the AusPROM and (3) establish if the QoR-15 PROM has concurrent validity with the EQ-5D-5L. Methods and analysis Phase I will identify staff barriers and facilitators for the implementation of the AusPROM recommendations using a Delphi technique. Phase II will determine QoR-15 acceptability for elective surgery patients across four pilot hospitals, using the AusPROM recommendations. For phase II, in addition to a consumer focus group, patients will complete brief acceptability surveys, incorporating the QoR-15, in the week prior to surgery, in the week following surgery and 4 weeks postsurgery. The primary endpoint will be 4 weeks postsurgery. Phase III will be the national implementation of the AusPROM (29 hospitals) and the concurrent validity of the QoR-15 and generic EQ-5D-5L. This protocol adopts the Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trials Protocols guidelines. Ethics and dissemination The results will be disseminated via public forums, conferences and peer-reviewed journals. Ethics approval: La Trobe University (HEC20479). Trial registration number ACTRN12621000298819 (Phase I and II) and ACTRN12621000969864 (Phase III)
Wenyan Li, Lan Guo, Sheng Zhang, Wanxin Wang, Xiaoliang Chen, Qian Li,
Published: 16 September 2021
by BMJ
Abstract:
Objectives This study was conducted to estimate whether emotional and behavioural problems mediate the association between sexual minority status and suicidal behaviour among Chinese adolescents. We also tested whether such mediation is moderated by the sex assigned at birth. Design Cross-sectional observational study. Setting A secondary analysis of the cross-sectional data collected from 7th-grade to 12th-grade students in junior high schools (n=36), senior high schools (n=24) and vocational high schools (n=12) in six cities of Guangdong Province, China. A multistage, stratified cluster, random sampling method was used in the 2019 School-based Chinese Adolescents Health Survey. Participants A total of 16 663 students aged 11–20 years. Outcome measures Two main psychological and mental health outcomes: (1) self-reported version of the Strengths and Difficulties Questionnaire to measure emotional and behavioural problems; and (2) presence of suicidal ideation and suicide attempts in the past 12 months. Results Emotional and behavioural problems (peer problems, emotional problems, conduct problems and hyperactivity) partially mediated the effects of sexual minority status on suicidal ideation (indirect effect=0.020, 95% CI 0.015 to 0.025) and suicide attempts (indirect effect=0.012, 95% CI 0.009 to 0.016), accounting for 18.18% and 14.46% of the total effect, respectively. Further moderated mediation analyses revealed a greater risk of suicidality among sexual minority girls. Conclusions Emotional and behavioural problems partially explained the increased risk of suicidality among sexual minority adolescents, and appreciably higher among sexual minority girls than boys. To prevent subsequent suicidality, the risks of emotional and behavioural problems in sexual minority adolescents should be identified at an early stage and reduced by means of preventive measures.
, Sophie Walford, David Howe
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2020-241412

Abstract:
A 34-year-old woman with a history of congenital hypothyroidism and 15 years of obstructive sleep apnoea was admitted with a left submandibular swelling secondary to a dental infection. A CT scan of the neck identified an incidental 27 mm tongue base mass and the absence of any cervical thyroid tissue. This mass was not observable on examination of the oropharynx but was seen on fine nasendoscopy while thyroid function tests showed good thyroid stimulating hormone suppression. Her acute dental infection was treated and, following multidisciplinary team discussion, she was diagnosed with an ectopic lingual thyroid. She was offered different management options including no intervention and radio-iodide treatment but opted for transoral robotic resection. The lesion was resected en bloc with clear margins and histology confirmed lingual thyroid tissue. Since the procedure, she has remained free of sleep apnoea with a significantly improved quality of life.
Mikako Nishida, Nahoko Yamashita, Taisaku Ogawa, Keita Koseki, Eiji Warabi, Tomoyuki Ohue, Masaaki Komatsu, , , Eiryo Kawakami, et al.
Published: 16 September 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-002954

Abstract:
Background Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging. However, the underlying mechanism of Met-dependent antitumor immunity remains to be elucidated. Methods MitoTEMPO, a scavenger of mitochondrial superoxide, abolished the antitumor effect of Met, but not antiprogrammed cell death (PD-1) antibody (Ab) treatment. Consequently, we studied the mechanism of the Met-induced antitumor effect. Expressions of glucose transporter (Glut)-1, mitochondrial reactive oxygen species (mtROS), interferon (IFN)-γ, Ki67, autophagy markers, activation markers for NF-E2-related factor 2 (Nrf2), and mammalian target of rapamaycin complex 1 (mTORC1) in CD8+ tumor-infiltrating T lymphocytes (CD8TILs) were examined by flow cytometry analysis. In addition, conditional knockout mice for Nrf2 and p62 were used to detect these markers, together with the monitoring of in vivo tumor growth. RNA sequencing was performed for CD8TILs and tumor cells. Melanoma cells containing an IFN-γ receptor (IFNγR) cytoplasmic domain deletion mutant was overexpressed and used for characterization of the metabolic profile of those tumor cells using a Seahorse Flux Analyzer. Results Met administration elevates mtROS and cell surface Glut-1, resulting in the production of IFN-γ in CD8TILs. mtROS activates Nrf2 in a glycolysis-dependent manner, inducing activation of autophagy, glutaminolysis, mTORC1, and p62/SQSTM1. mTORC1-dependent phosphorylation of p62 at serine 351 (p-p62(S351)) is also involved in activation of Nrf2. Conditional deletion of Nrf2 in CD8TILs abrogates mTORC1 activation and antitumor immunity by Met. In synergy with the effect of anti-PD-1 Ab, Met boosts CD8TIL proliferation and IFN-γ secretion, resulting in decreased glycolysis and oxidative phosphorylation in tumor cells. Consequently, Glut-1 is elevated in CD8TILs, together with the expansion of activated dendritic cells. Moreover, tumor cells lacking in IFNγR signaling abolish IFN-γ production and proliferation of CD8TILs. Conclusions We found that Met stimulates production of mtROS, which triggers Glut-1 elevation and Nrf2 activation in CD8TILs. Nrf2 activates mTORC1, whereas mTORC1 activates Nrf2 in a p-p62(S351)-dependent manner, thus creating a feedback loop that ensures CD8TILs’ proliferation. In combination with anti-PD-1 Ab, Met stimulates robust proliferation of CD8TILs and IFN-γ secretion, resulting in an IFN-γ-dependent reprogramming of the tumor microenvironment.
Priya K Nair, Beena R Varma, Ravi Veeraraghavan,
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-243319

Abstract:
Canalicular adenoma is a unique, rare, benign salivary gland neoplasm whose reported prevalence varies in different studies. According to literature, this neoplasm has a marked predilection to occur in the upper lip of elderly women. Histological features are usually distinctive and diagnostic. This neoplasm has good prognosis after conservative surgical management but the propensity of multifocal nature and recurrence of this lesion mandates regular follow-up. This case report illustrates the case of a canalicular adenoma in the palate in a 71-year-old male patient. Here, we discuss the differential diagnosis with a brief review of literature.
, Juliette E Hommes, Todor K Krastev, Daniëlle Derks, Mikko Larsen, , Ute Schmidbauer, Jan Maerten Smit, Tik Tan, Kim Wehrens, et al.
Published: 16 September 2021
by BMJ
Abstract:
Introduction Pioneers have shown that it is possible to reconstruct a full breast using just autologous fat harvested by liposuction or autologous fat transfer (AFT). This study describes the first multicentre randomised study protocol to thoroughly investigate the effectiveness of AFT to reconstruct full breasts following mastectomy procedures (primarily and delayed). Methods and analysis This study is designed as a multicentre, randomised controlled clinical superiority trial with a 1:1 allocation ratio. A total of 196 patients (98 patients per treatment arm) are aimed to be included. Patients who wish to undergo breast reconstruction with either one of the two techniques are randomly allocated into the AFT group (intervention) or the tissue-expander/prosthesis group (control). The primary outcome measure for the quality of life is measured by the validated BREAST-Q questionnaire. Ethics and dissemination Approval for this study was obtained from the medical ethics committee of Maastricht University Medical Centre/Maastricht University; the trial has been registered at ClinicalTrials.gov. The results of this randomised controlled trial will be presented at scientific meetings as abstracts for poster or oral presentations and published in peer-reviewed journals. Trial status Enrolment into the trial has started in October 2015. Data collection and data analysis are expected to be completed in December 2021. Trial registration number NCT02339779.
Min Tao, Xiaoyan Ma, Xiaoling Pi, Yingfeng Shi, Lunxian Tang, Yan Hu, Hui Chen, Xun Zhou, Lin Du, Yongbin Chi, et al.
Published: 16 September 2021
by BMJ
Abstract:
Objective Women in different age phases have different metabolism and hormone levels that influence the production and excretion of uric acid. We aimed to investigate the prevalence and related factors of hyperuricaemia among women in various age phases. Study design Observational, cross-sectional study. Setting Data were obtained from women at three health check-up centres in Shanghai. Participants Adult women from three health check-up centres were recruited. Exclusion criteria were individuals with pregnancy, cancer, incomplete information. Finally, 11 601 participants were enrolled. Results The prevalence rates of hyperuricaemia of total subjects were 11.15% (95% CIs 10.57% to 11.72%). The prevalence of hyperuricaemia in 18–29, 30–39, 40–49, 50–59, 60–69 and ≥70 years old was 6.41% (95% CI 4.97% to 7.86%), 5.63% (4.71% to 6.55%), 6.02% (5.01%% to 7.03%), 11.51% (10.19% to 12.82%), 16.49% (15.03% to 17.95%) and 23.98% (21.56% to 26.40%), respectively. Compared with 18–29 years old, the ORs for hyperuricaemia in other age phases were 0.870 (95% CI 0.647 to 1.170, p=0.357), 0.935 (0.693 to 1.261, p=0.659), 1.898 (1.444 to 2.493, p<0.001), 2.882 (2.216 to 3.748, p<0.001) and 4.602 (3.497 to 6.056, p<0.001), respectively. During the 18–29 years old, the related factors for hyperuricaemia were obesity and dyslipidaemia. During the 30–59 years old, the related factors were obesity, dyslipidaemia, hypertension and chronic kidney disease (CKD). Over the 60 years old, the occurrence of hyperuricaemia was mainly affected by obesity, dyslipidaemia and CKD, while hypertension cannot be an impact factor for hyperuricaemia independently of obesity and dyslipidaemia. Conclusion After 50 years old, the prevalence of hyperuricaemia in Shanghai women has increased significantly and reaches the peak after 70. Obesity and dyslipidaemia are two main related factors for hyperuricaemia during all ages, while diabetes mellitus and nephrolithiasis have no relationship with hyperuricaemia throughout. CKD is an independent impact factor for hyperuricaemia after 30 years old.
, Nicole Korman, Joseph Firth, Davy Vancampfort, Trevor Thompson, Brendon Stubbs
Published: 16 September 2021
by BMJ
British Journal of Sports Medicine; https://doi.org/10.1136/bjsports-2021-103984

Abstract:
Objective High-intensity interval training (HIIT) is a safe and feasible form of exercise. The aim of this meta-analysis was to investigate the mental health effects of HIIT, in healthy populations and those with physical illnesses, and to compare the mental health effects to non-active controls and other forms of exercise. Design Random effects meta-analyses were undertaken for randomised controlled trials (RCTs) comparing HIIT with non-active and/or active (exercise) control conditions for the following coprimary outcomes: mental well-being, symptoms of depression, anxiety and psychological stress. Positive and negative affect, distress and sleep outcomes were summarised narratively. Data sources Medline, PsycINFO, Embase and CENTRAL databases were searched from inception to 7 July 2020. Eligibility criteria for selecting studies RCTs that investigated HIIT in healthy populations and/or those with physical illnesses and reported change in mental well-being, depression, anxiety, psychological stress, positive/negative affect, distress and/or sleep quality. Results Fifty-eight RCTs were retrieved. HIIT led to moderate improvements in mental well-being (standardised mean difference (SMD): 0.418; 95% CI: 0.135 to 0.701; n=12 studies), depression severity (SMD: –0.496; 95% CI: −0.973 to −0.020; n=10) and perceived stress (SMD: −0.474; 95% CI: −0.796 to −0.152; n=4) compared with non-active controls, and small improvements in mental well-being compared with active controls (SMD:0.229; 95% CI: 0.054 to 0.403; n=12). There was a suggestion that HIIT may improve sleep and psychological distress compared with non-active controls: however, these findings were based on a small number of RCTs. Conclusion These findings support the use of HIIT for mental health in the general population. Level of evidence The quality of evidence was moderate-to-high according to the Grading of Recommendations Assessment, Development and Evaluation) criteria. PROSPERO registration number CRD42020182643
, Mark D Lyttle, Charlotte Munday, Steven Foster, Marc McNulty, Rebecca Platt, Michael Barrett, Emma Rogers, Sheena Durnin, Nida Jameel, et al.
Published: 16 September 2021
by BMJ
Archives of Disease in Childhood; https://doi.org/10.1136/archdischild-2021-322586

Abstract:
Objective To report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC). Design Retrospective multicentre cohort study. Patients Febrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019. Main outcome measures The sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI. Setting Six paediatric Emergency Departments in the UK/Ireland. Results 555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001). Conclusion None of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making. Trial registration number NCT04196192.
, Karl-Fredrik Eriksson, Per Wollmer, Gunnar Engström
Published: 16 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001043

Abstract:
Background Many of those who suffer from a first acute coronary event (CE) die suddenly during the day of the event, most of them die outside hospital. Poor lung function is a strong predictor of future cardiac events; however, it is unknown whether the pattern of lung function impairment differs for the prediction of sudden cardiac death (SCD) versus non-fatal CEs. We examined measures of lung function in relation to future SCD and non-fatal CE in a population-based study. Methods Baseline spirometry was assessed in 28 584 middle-aged subjects, without previous history of CE, from the Malmö Preventive Project. The cohort was followed prospectively for incidence of SCD (death on the day of a first CE, inside or outside hospital) or non-fatal CE (survived the first day). A modified version of the Lunn McNeil’s competing risk method for Cox regression was used to run models for both SCD and non-fatal CE simultaneously. Results A 1-SD reduction in forced expiratory volume in 1 s (FEV1) was more strongly associated with SCD than non-fatal CE even after full adjustment (FEV1: HR for SCD: 1.23 (1.15 to 1.31), HR for non-fatal CE 1.08 (1.04 to 1.13), p value for equal associations=0.002). Similar associations were found for forced vital capacity (FVC) but not FEV1/FVC. The results remained significant even in life-long never smokers (FEV1: HR for SCD: 1.34 (1.15 to 1.55), HR for non-fatal CE: 1.11 (1.02 to 1.21), p value for equal associations=0.038). Similar associations were seen when % predicted values of lung function measures were used. Conclusions Low FEV1 is associated with both SCD and non-fatal CE, but consistently more strongly associated with future SCD. Measurement with spirometry in early life could aid in the risk stratification of future SCD. The results support the use of spirometry for a global assessment of cardiovascular risk.
Xueqing Peng, Zhiguang Li, Chi Zhang, Rui Liu, Yongzhi Jiang, Jiayu Chen, Zixin Qi, , Shiqi Zhao, Meng Zhou, et al.
Published: 16 September 2021
by BMJ
Abstract:
Objective To investigate the determinants of willingness and practice of physicians’ online medical services (OMS) uptake based on social ecosystem theory, so as to formulate OMS development strategies. Design Cross-sectional survey. Setting Research was conducted in two comprehensive hospitals and two community hospitals in Jiangsu, China, and the data were gathered from 1 June to 31 June 2020. Participants With multistage sampling, 707 physicians were enrolled in this study. Outcome measure Descriptive statistics were reported for the basic characteristics. χ2 test, Mann-Whitney U test and Spearman’s correlation analysis were used to perform univariate analysis. Linear regression and logistic regression were employed to examine the determinants of physicians’ OMS uptake willingness and actual uptake, respectively. Results The mean score of the physicians’ OMS uptake willingness was 17.33 (range 5–25), with an SD of 4.39, and 53.3% of them reported having conducted OMS. In the micro system, factors positively associated with willingness included holding administrative positions (b=1.03, p<0.05), OMS-related awareness (b=1.32, p<0.001) and OMS-related skills (b=4.88, p<0.001); the determinants of actual uptake included holding administrative positions (OR=2.89, 95% CI 1.59 to 5.28, p<0.01), OMS-related awareness (OR=1.90, 95% CI 1.22 to 2.96, p<0.01), OMS-related skills (OR=2.25, 95% CI 1.35 to 3.74, p<0.01) and working years (OR=2.44, 95% CI 1.66 to 3.59, p<0.001). In the meso system, the hospital’s incentive mechanisms (b=0.78, p<0.05) were correlated with willingness; hospital advocated for OMS (OR=2.34, 95% CI 1.21 to 4.52, p<0.05), colleagues’ experiences (OR=3.81, 95% CI 2.25 to 6.45, p<0.001) and patients’ consultations (OR=2.93, 95% CI 2.02 to 4.25, p<0.001) were determinants of actual uptake. In the macro system, laws and policies were correlated with willingness (b=0.73, p<0.05) and actual uptake (OR=1.98, 95% CI 1.31 to 2.99, p<0.01); media orientation was also associated with willingness (b=0.74, p<0.05). Conclusion Multiple determinants influence physicians’ OMS application. Comprehensive OMS promotion strategies should be put forward from multidimensional perspectives including the micro, meso and macro levels.
Julia R Schiff, Benjamin P Fiorillo, Raha Sadjadi, , Judah K Gruen, Lauren M Gensler
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-244316

Abstract:
A 59-year-old woman presented to the hospital with acute, hypoactive altered mental status. Her symptoms had begun 3 days prior when she developed hallucinations, urinary and faecal incontinence, and somnolence. She also exhibited confabulations, amnesia, motor memory loss and a wide-based gait. Medical, psychiatric and neurological evaluations including imaging and laboratory workup were unrevealing. Treatment for possible Wernicke encephalopathy and psychosis with high-dose intravenous thiamine and antipsychotic medications did not lead to improvement. After discharge, a send-out cerebrospinal fluid autoimmune encephalitis panel resulted positive for the newly identified neuronal inositol triphosphate receptor one (ITPR1) antibody. This prompted readmission for intravenous steroids, plasmapheresis and intravenous immunoglobulin, which yielded mild clinical improvement. Here, we describe confabulations and psychiatric symptoms as novel manifestations of the primary presentation of anti-ITPR1 encephalitis in an effort to promote faster recognition of this disease and early initiation of treatment in suspected cases.
Shajith Anoop S, Riddhi Dasgupta, Grace Rebekah, Arun Jose, Mercy Prem Inbakumari, Geethanjali Finney, Nihal Thomas
Published: 16 September 2021
by BMJ
BMJ Open Diabetes Research & Care, Volume 9; https://doi.org/10.1136/bmjdrc-2021-002414

Abstract:
Introduction We aimed to compare the predictive accuracy of surrogate indices namely the lipid accumulation product (LAP) index, homeostatic model of assessment of insulin resistance (HOMA-IR), fasting glucose-insulin ratio (FG-IR) and the quantitative-insulin sensitivity check index (QUICKI), against the M value of hyperinsulinemic-euglycemic clamp (HEC), and to determine a cut-off value for the LAP index to predict risk of insulin resistance in non-obese (body mass index <21 kg/m2), normoglycemic, Asian Indian males from Southern India. Research design and methods Data of HEC studies performed in 108 non-obese, normoglycemic, Asian Indian males was obtained retrospectively and the M value (a measure of whole-body insulin sensitivity) was calculated. The M value is the rate of whole-body glucose metabolism at the hyperinsulinemic plateau (a measure of insulin sensitivity) and is calculated between 60 and 120 min after the start of the insulin infusion in the HEC procedure. The LAP index, the HOMA-IR, FG-IR and QUICKI were calculated. Spearman’s correlation and logistic regression analysis were performed. Cut-off value for the LAP index was obtained using receiver operating characteristics with area under curve (AUC) analysis at 95% CI. P value <0.05 was considered to be statistically significant. Results Significant negative correlation was observed for the M value with LAP index (r=−0.39, p<0.001) while significant positive correlation was noted with FG-IR (r=0.25; p<0.01) and QUICKI (r=0.22; p<0.01). The LAP index cut-off value ≥33.4 showed 75% sensitivity and 75% specificity with AUC (0.72) to predict risk of insulin resistance in this cohort. Conclusion The LAP index showed higher predictive accuracy for the risk of insulin resistance as compared with HOMA-IR, QUICKI and FG-IR in non-obese, normoglycemic Asian Indian males from Southern India.
Ralph Rommualdo Abareta Zuniega, Julian Alejandro Santos, Romelito Jose Galvan Galsim, Jonathan Saputil Elevazo
Published: 16 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-242439

Abstract:
Dural venous sinus ectasia is a rare anomaly characterised by the formation of a large vascular lake within the leaves of the dural sinuses, usually associated with thrombosis. These lesions can cause brain compression, cardiac insufficiency and disseminated intravascular coagulation, which may lead to poor prognosis. We present the case of a neonate who presented with an intracranial mass on prenatal ultrasound. Postnatal transcranial ultrasonography, cranial CT and cranial MRI demonstrated a large lesion predominantly occupying the dural sinus confluence, extending into the sagittal sinus, straight sinus and right transverse sinus. The left marginal sinus remains unfused and patent. Concomitant arteriovenous malformations were evident in the median interhemispheric fissure and the left Sylvian fissure. There are several published case reports and case series describing malformations of the dural sinuses in perinatal and neonatal patients in recent years, but this case is unique in that: (1) there is the presence of a vascular malformation concomitant to the dural sinus ectasia and (2) it highlights the importance of imaging in clinching the diagnosis of giant dural venous sinus ectasia, as it is often misdiagnosed as more common conditions such as extra-axial intracranial haemorrhage.
, Naji Younes, , Joshua I Barzilay, Mary Ann Banerji, Robert M Cohen, Erica V Gonzalez, Faramarz Ismail-Beigi, Kieren J Mather, Philip Raskin, et al.
Published: 16 September 2021
by BMJ
BMJ Open Diabetes Research & Care, Volume 9; https://doi.org/10.1136/bmjdrc-2021-002264

Abstract:
Introduction The shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone. Research design and methods This is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed <10 years who underwent 2-hour 75 g OGTT at baseline as part of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Insulin sensitivity (homeostasis model of insulin sensitivity, HOMA2-S) and β-cell function (early, late, and total incremental insulin and C peptide responses adjusted for HOMA2-S) were calculated. Glucose curve shape was classified as monophasic, biphasic, or continuous rise. Results The monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all p<0.05 vs monophasic and continuous rise). Compared with the monophasic subgroup, the continuous rise subgroup had similar early insulin (p=0.3) and C peptide (p=0.6) responses but lower late insulin (p<0.001) and total insulin (p=0.008) and C peptide (p<0.001) responses. Conclusions Based on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates. Trial registration number NCT01794143.
Kelly Chu, Batool Alharahsheh, Naveen Garg, Payal Guha
Published: 14 September 2021
by BMJ
BMJ Health & Care Informatics, Volume 28; https://doi.org/10.1136/bmjhci-2021-100389

Abstract:
Background The COVID-19 pandemic has necessitated efficient and accurate triaging of patients for more effective allocation of resources and treatment. Objectives The objectives are to investigate parameters and risk stratification tools that can be applied to predict mortality within 90 days of hospital admission in patients with COVID-19. Methods A literature search of original studies assessing systems and parameters predicting mortality of patients with COVID-19 was conducted using MEDLINE and EMBASE. Results 589 titles were screened, and 76 studies were found investigating the prognostic ability of 16 existing scoring systems (area under the receiving operator curve (AUROC) range: 0.550–0.966), 38 newly developed COVID-19-specific prognostic systems (AUROC range: 0.6400–0.9940), 15 artificial intelligence (AI) models (AUROC range: 0.840–0.955) and 16 studies on novel blood parameters and imaging. Discussion Current scoring systems generally underestimate mortality, with the highest AUROC values found for APACHE II and the lowest for SMART-COP. Systems featuring heavier weighting on respiratory parameters were more predictive than those assessing other systems. Cardiac biomarkers and CT chest scans were the most commonly studied novel parameters and were independently associated with mortality, suggesting potential for implementation into model development. All types of AI modelling systems showed high abilities to predict mortality, although none had notably higher AUROC values than COVID-19-specific prediction models. All models were found to have bias, including lack of prospective studies, small sample sizes, single-centre data collection and lack of external validation. Conclusion The single parameters established within this review would be useful to look at in future prognostic models in terms of the predictive capacity their combined effect may harness.
Sergej Godec, Michael Jozef Gradisek, Tomislav Mirkovic,
Published: 14 September 2021
by BMJ
Regional Anesthesia & Pain Medicine; https://doi.org/10.1136/rapm-2021-102498

Abstract:
Background Tranexamic acid (TXA) decreases hemorrhage-related mortality in trauma patients and is increasingly being used during obstetric and orthopedic surgeries. Inadvertent intrathecal injection of TXA is a rare, potentially lethal event leading to dose-dependent cardiotoxicity and neurotoxicity. TXA enhances neuronal excitation by antagonizing inhibitory γ-aminobutyric acid type A and glycine receptors. Until now, mechanistic-based pharmacological treatments targeting multiple central nervous system receptors have been advocated for use in such cases, with no data on intrathecal TXA elimination techniques. Case presentation A patient scheduled for hip surgery accidentally received 350 mg of intrathecal TXA instead of levobupivacaine. The clinical picture progressed from spinal segmental myoclonus to generalized convulsions and malignant arrhythmias. The treatment consisted of ventriculolumbar perfusion with normal saline at a rate of 50 mL/hour starting 5 hours after TXA administration and inhalational sedation with sevoflurane, in addition to drugs acting on multiple receptors at different central nervous system levels. Over 2 months the neurological status improved, although it was not complete. Conclusions For the first time, the feasibility and possible clinical efficacy of combined treatment with ventriculolumbar perfusion and inhalational sedation with sevoflurane were demonstrated. A referral to a neurosurgical facility is recommended in patients with acute TXA-induced neurotoxicity and cardiotoxicity.
Aditya Kallimath, Reema Garegrat, Suprabha Patnaik, Pradeep Suryawanshi
Published: 14 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-246100

Abstract:
Most reports of COVID-19 in neonates suggest that they are infected postnatally and present with gastrointestinal or respiratory symptoms. We describe a neonate who had community-acquired COVID-19, and presented with late-onset sepsis and developed dyselectrolytemia. The 26-day-old male baby had fever, feed refusal and shock. Rapid antigen test for SARS-CoV-2 by nasopharyngeal swab was positive and levels of circulating inflammatory markers were high. The baby was supported with antibiotics, and inotropic and vasopressor drugs. He had seizures and bradycardia due to dyselectrolytemia on day 2 of admission. On day 3, he had respiratory distress, with non-specific chest radiographic findings, and was managed with non-invasive support for 24 hours. The baby was discharged after 8 days. On serial follow-up, he was breastfeeding well and gaining weight appropriately with no morbidity. Our report highlights a unique presentation of COVID-19, with late-onset infection and shock-like features along with dyselectrolytemia and seizures.
Brandon Wen Bing Chua, Vinh Anh Huynh, Jing Lou, Fang Ting Goh, , Yot Teerawattananon, Hwee Lin Wee
Published: 14 September 2021
by BMJ
Abstract:
Introduction Several treatment options are available for COVID-19 to date. However, the use of a combination of non-pharmaceutical interventions (NPIs) is necessary for jurisdictions to contain its spread. Although the implementation cost of NPIs may be low from the healthcare system perspective, it can be costly when considering the indirect costs from the societal perspective. COVID-19 vaccination campaigns have begun in several countries worldwide. Nonetheless, the quantity of vaccines available remain limited over the next 1 to 2 years. A tool for informing vaccine prioritisation that considers both cost and effectiveness will be highly useful. This study aims to identify the most cost-effective combination of COVID-19 response policies, using Singapore as an example. Methods and analysis An age-stratified Susceptible-Exposed-Infectious-Recovered model will be used to generate the number of infections stratified by disease severity under different intervention scenarios. Polices of interest include test-trace-isolate, travel restriction, compulsory face mask and hygiene practices, social distancing, dexamethasone/remdesivir therapy and vaccination. The latest phase 3 trial results and the WHO Target Product Profiles for COVID-19 vaccines will be used to model vaccine characteristics. A cost (expected resource utilisation and productivity losses) and quality-adjusted life years (QALYs) will be attached to these outputs for a cost-utility analysis. The primary outcome measure will be the incremental cost-effectiveness ratio generated from the incremental cost of policy alternatives expressed as a ratio of the incremental benefits (QALYs gained). Efficacy of policy options will be gathered from literature review and from its observed impacts in Singapore. Cost data will be gathered from healthcare institutions, Ministry of Health and published data. Sensitivity analysis such as threshold analysis and scenario analysis will be conducted. Ethics and dissemination Ethics approval was not required for this study. The study findings will be disseminated through peer-reviewed journals.
Grégoire Muller, Toufik Kamel, Damien Contou, , Maëlle Martin, , Jean-Claude Lacherade, Florence Boissier, Alexandra Monnier, Sylvie Vimeux, et al.
Published: 14 September 2021
by BMJ
Abstract:
Introduction The use of peripheral indwelling arterial catheter for haemodynamic monitoring is widespread in the intensive care unit and is recommended in patients with shock. However, there is no evidence that the arterial catheter could improve patient’s outcome, whereas the burden of morbidity generated is significant (pain, thrombosis, infections). We hypothesise that patients with shock may be managed without an arterial catheter. Methods and analysis The EVERDAC study is an investigator-initiated, pragmatic, multicentre, randomised, controlled, open-label, non-inferiority clinical trial, comparing a less invasive intervention (ie, no arterial catheter insertion until felt absolutely needed, according to predefined safety criteria) or usual care (ie, systematic arterial catheter insertion in the early hours of shock). 1010 patients will be randomised with a 1:1 ratio in two groups according to the strategy. The primary outcome is all-cause mortality by 28 days after inclusion. A health economic analysis will be carried out. Ethics and dissemination The study has been approved by the Ethics Committee (Comité de Protection des Personnes Île de France V, registration number 61606 CAT 2, 19 july 2018) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. Trial registration number NCT03680963.
, Ville Aalto, Jaana Pentti, Tuula Oksanen, Mika Kivimäki,
Published: 14 September 2021
by BMJ
Occupational and Environmental Medicine; https://doi.org/10.1136/oemed-2021-107745

Abstract:
Objectives To examine the associations of COVID-19-related changes in work with perceptions of psychosocial work environment and employee health. Methods In a cohort of 24 299 Finnish public sector employees, psychosocial work environment and employee well-being were assessed twice before (2016 and 2018=reference period) and once during (2020) the COVID-19 pandemic. Those who reported a change (=‘Exposed’) in work due to the pandemic (working from home, new tasks or team reorganisation) were compared with those who did not report such change (=‘Non-exposed’). Results After adjusting for sex, age, socioeconomic status and lifestyle risk score, working from home (44%) was associated with greater increase in worktime control (standardised mean difference (SMD)Exposed=0.078, 95% CI 0.066 to 0.090; SMDNon-exposed=0.025, 95% CI 0.014 to 0.036), procedural justice (SMDExposed=0.101, 95% CI 0.084 to 0.118; SMDNon-exposed=0.053, 95% CI 0.038 to 0.068), workplace social capital (SMDExposed=0.094, 95% CI 0.077 to 0.110; SMDNon-exposed=0.034, 95% CI 0.019 to 0.048), less decline in self-rated health (SMDExposed=−0.038, 95% CI −0.054 to –0.022; SMDNon-exposed=−0.081, 95% CI −0.095 to –0.067), perceived work ability (SMDExposed=−0.091, 95% CI −0.108 to –0.074; SMDNon-exposed=−0.151, 95% CI −0.167 to –0.136) and less increase in psychological distress (risk ratio (RR)Exposed=1.06, 95% CI 1.02 to 1.09; RRNon-exposed=1.16, 95% CI 1.13 to 1.20). New tasks (6%) were associated with greater increase in psychological distress (RRExposed=1.28, 95% CI 1.19 to 1.39; RRNon-exposed=1.10, 95% CI 1.07 to 1.12) and team reorganisation (5%) with slightly steeper decline in perceived work ability (SMDExposed=−0.151 95% CI −0.203 to –0.098; SMDNon-exposed=−0.124, 95% CI −0.136 to –0.112). Conclusion Employees who worked from home during the pandemic had more favourable psychosocial work environment and health, whereas those who were exposed to work task changes and team reorganisations experienced more adverse changes.
, Kelsey Flott, Roberto Fernandez Crespo, , Gianluca Fontana, , Ara Darzi, Sarah Elkin
Published: 14 September 2021
by BMJ
Abstract:
Objectives To determine the safety and effectiveness of home oximetry monitoring pathways for patients with COVID-19 in the English National Health Service. Design Retrospective, multisite, observational study of home oximetry monitoring for patients with suspected or proven COVID-19. Setting This study analysed patient data from four COVID-19 home oximetry pilot sites in England across primary and secondary care settings. Participants A total of 1338 participants were enrolled in a home oximetry programme across four pilot sites. Participants were excluded if primary care data and oxygen saturations at rest at enrolment were not available. Data from 908 participants were included in the analysis. Interventions Home oximetry monitoring was provided to participants with a known or suspected diagnosis of COVID-19. Participants were enrolled following attendance to emergency departments, hospital admission or referral through primary care services. Results Of 908 patients enrolled into four different COVID-19 home oximetry programmes in England, 771 (84.9%) had oxygen saturations at rest of 95% or more, and 320 (35.2%) were under 65 years of age and without comorbidities. 52 (5.7%) presented to hospital and 28 (3.1%) died following enrolment, of which 14 (50%) had COVID-19 as a named cause of death. All-cause mortality was significantly higher in patients enrolled after admission to hospital (OR 8.70 (2.53–29.89)), compared with those enrolled in primary care. Patients enrolled after hospital discharge (OR 0.31 (0.15–0.68)) or emergency department presentation (OR 0.42 (0.20–0.89)) were significantly less likely to present to hospital than those enrolled in primary care. Conclusions This study finds that home oximetry monitoring can be a safe pathway for patients with COVID-19; and indicates increases in risk to vulnerable groups and patients with oxygen saturations <95% at enrolment, and in those enrolled on discharge from hospital. Findings from this evaluation have contributed to the national implementation of home oximetry across England.
Shruti Sinha, Bhaimangesh Bhanudas Naik, Jaishree Ghanekar
Published: 14 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-244830

Abstract:
A 48-year-old woman presented with sudden-onset altered sensorium 2 days after a snake bite (unidentified species) and was found to have a large right frontal intracerebral haemorrhage (ICH) with transtentorial herniation (TTH) causing brain stem compression. A day later, neurological examination revealed internuclear ophthalmoplegia (INO) fitting the clinical description of wall eyed bilateral INO syndrome. INO is a rare ocular motor sign, the most common causes being brain stem infarction, haemorrhage or demyelinating disease. It rarely acts as a false localising sign, such as in this case, and in an even rarer cause for ICH, that is, haemotoxic snake bite without initial evidence of coagulopathy. An emphasis needs to be laid on detailed physical examination, often considered a lost art nowadays, to help detect subtle clinical signs which could herald ominous complications of conditions like TTH and help in early diagnosis and treatment of the same.
, Andrew Steptoe,
Published: 14 September 2021
by BMJ
Journal of Epidemiology and Community Health; https://doi.org/10.1136/jech-2021-216876

Abstract:
Background Governments have implemented a range of measures to tackle COVID-19, primarily focusing on changing citizens’ behaviours in order to lower the transmission of the virus. Few studies have looked at the patterns of compliance with different measures within individuals: whether people comply with all measures or selectively choose some but not others. Such research is important for designing interventions to increase compliance. Methods We used cross-sectional data from 20 947 UK adults in the COVID-19 Social Study collected from 17 November to 23 December 2020. Self-report compliance was assessed with six behaviours: mask wearing, hand washing, indoor household mixing, outdoor household mixing, social distancing and compliance with other guidelines. Patterns of compliance behaviour were identified using latent class analysis, and multinomial logistic regression was used to assess demographic, socioeconomic and personality predictors of behaviour patterns. Results We selected a four-latent class solution. Most individuals reported similar levels of compliance across the six behaviour measures. High level of compliance was the modal response. Lower self-reported compliance was related to young age, high risk-taking behaviour, low confidence in government and low empathy, among other factors. Looking at individual behaviours, mask wearing had the highest level of compliance while compliance with social distancing was relatively low. Conclusion Results suggest that individuals choose to comply with all guidelines, rather than some but not others. Strategies to increase compliance should focus on increasing general motivations to comply alongside specifically encouraging social distancing.
, Sofia El Oussoul, Amélie Pavard, Delphine Fabre, Caroline Cellard, Laurent Magaud, Fabien Subtil, Eleonore Damiolini, Eric Fakra, Julie Haesebaert
Published: 14 September 2021
by BMJ
Abstract:
Introduction The prognosis of first episode psychosis (FEP), which is a severe disorder, can be notably impaired by patients’ disengagement from healthcare providers. Coordinated specialty care with case management is now considered as the gold standard in this population, but there are still challenges for engagement with subsequent functional impairments. Youth-friendly and patient-centred clinical approaches are sought to improve engagement in patients with FEP. Mobile applications are widely used by young people, including patients with FEP, and can increase the youth friendliness of clinical tools. We hypothesise that a co-designed mobile application used during case management can improve functioning in patients with FEP as compared with usual case management practices. Methods and analysis A mobile case management application for planning and monitoring individualised care objectives will be co-designed with patients, caregivers and health professionals in a recovery-oriented approach. The application will be compared with usual case management practices in a multicentre, two-arm and parallel groups clinical trial. Patients will be recruited by specialised FEP teams. Impact on functioning will be assessed using the Personal and Social Performance Scale; the variation between baseline and 12 months in each group (control and active) will be the primary outcome. Ethics and dissemination This study has been approved by the Inserm Institutional Review Board IRB00003888 (Comité d’évaluation éthique de l’INSERM, reference number 20-647). The results of the study will be published in a peer-reviewed journal and presented at national and international conferences. We will also communicate the results to patients and family representatives’ associations. An optimised version of the application will be then disseminated through the French FEP network (Transition Network). Trial registration number ClinicalTrials.gov: NCT04657380
Sarah Fernández-Suárez, Giuliana Reyes-Florian, ,
Published: 14 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-244768

Abstract:
SARS-CoV-2 infection in children with primary immunodeficiency disease (PID) and its complications have not yet been well described, the course of COVID-19 can range from mild illness to death. We aim to report the case of a child with a PID who develop a severe and persistent pulmonary COVID-19 infection. We present chronologically his clinical course, tests, interventions and radiological findings showing his irregular evolution and poor response to infection. This case highlights the need to accurately monitor the immune response in these cases to try to stop the progression of the damage.
, Fan Lee, Agatha Bula, Clement Mapanje, Billy Rodwell Phiri, Nenani Kamtuwange, Mercy Tsidya, , Lameck Chinula
Published: 14 September 2021
by BMJ
Abstract:
Introduction Cervical cancer is the leading cause of cancer deaths among women in Malawi, but preventable through screening. Malawi primarily uses visual inspection with acetic acid (VIA) for screening, however, a follow-up for positive screening results remains a major barrier, in rural areas. We interviewed women who underwent a community-based screen-and-treat campaign that offered same-day treatment with thermocoagulation, a heat-based ablative procedure for VIA-positive lesions, to understand the barriers in accessing post-treatment follow-up and the role of male partners in contributing to, or overcoming these barriers. Methods We conducted in-depths interviews with 17 women recruited in a pilot study that evaluated the safety and acceptability of community-based screen-and-treat programme using VIA and thermocoagulation for cervical cancer prevention in rural Lilongwe, Malawi. Ten of the women interviewed presented for post-treatment follow-up at the healthcare facility and seven did not. The interviews were analysed for thematic content surrounding barriers for attending for follow-up and role of male partners in screening. Results Transportation was identified as a major barrier to post-thermocoagulation follow-up appointment, given long distances to the healthcare facility. Male partners were perceived as both a barrier for some, that is, not supportive of 6-week post-thermocoagulation abstinence recommendation, and as an important source of support for others, that is, encouraging follow-up attendance, providing emotional support to maintaining post-treatment abstinence and as a resource in overcoming transportation barriers. Regardless, the majority of women desired more male partner involvement in cervical cancer screening. Conclusion Despite access to same-day treatment, long travel distances to health facilities for post-treatment follow-up visits remained a major barrier for women in rural Lilongwe. Male partners were identified both as a barrier to, and an important source of support for accessing and completing the screen-and-treat programme. To successfully eliminate cervical cancer in Malawi, it is imperative to understand the day-to-day barriers women face in accessing preventative care.
, Mai Khanh Le, Chou Chuen Yu, Sok Ying Liaw, Tanya Tierney, Yun Ying Ho, Evelyn Lim, Daphne Lim, , Colin Ngeow, et al.
Published: 14 September 2021
by BMJ
Abstract:
Objective To define clinical empathy from the perspective of healthcare workers and patients from a multicultural setting. Design Grounded theory approach using focus group discussions. Setting A health cluster in Singapore consisting of an acute hospital, a community hospital, ambulatory care teams, a medical school and a nursing school. Participants 69 participants including doctors, nurses, medical students, nursing students, patients and allied health workers. Main outcome measures A robust definition of clinical empathy. Results The construct of clinical empathy is consistent across doctors, nurses, students, allied health and students. Medical empathy consists of an inner sense of empathy (imaginative, affective and cognitive), empathy behaviour (genuine concern and empathic communication) and a sense of connection (trust and rapport). This construct of clinical empathy is similar to definitions by neuroscientists but challenges a common definition of clinical empathy as a cognitive process with emotional detachment. Conclusions This paper has defined clinical empathy as ‘a sense of connection between the healthcare worker and the patient as a result of perspective taking arising from imaginative, affective and cognitive processes, which are expressed through behaviours and good communication skills that convey genuine concern’. A clear and multidimensional definition of clinical empathy will improve future education and research efforts in the application and impact of clinical empathy.
Henryk Bukowski, Nor Faizaah Ahmad Kamal, , Gabriella Rizzo,
Published: 14 September 2021
by BMJ
Abstract:
Objective Physicians’ cognitive empathy is associated with improved diagnosis and better patient outcomes. The relationship between self-reported and performance-based measures of cognitive empathic processes is unclear. Design Cross-sectional analysis of the association between medical students’ empathy scale scores and their empathic performance in a visuospatial perspective-taking (VPT) task. Participants Undergraduate medical students across two European medical schools (n=194). Primary and secondary outcome measures Two self-report empathy and one performance-based perspective-taking outcome: Jefferson Scale of Physician Empathy (JSPE); Empathy Quotient (EQ); Samson’s level-1 VPT task. Results Higher scores on the ‘standing in patient’s shoes’ subscale of the JSPE were associated with a lower congruency effect (as well as lower egocentric and altercentric biases) in the VPT (B=−0.007, 95% CI=−0.013 to 0.002, p<0.05), which reflects an association with better capacity to manage conflicting self-other perspectives, also known as self-other distinction. Lower egocentric bias was also associated with higher scores on the ‘social skills’ EQ subscale (B=−10.17, 95% CI=−17.98 to 2.36, p<0.05). Additionally, selection of a ‘technique-oriented’ clinical specialty preference was associated with a higher self-perspective advantage in the VPT, reflecting greater attentional priority given to the self-perspective. Conclusions We show that self-assessment scores are associated with selected performance-based indices of perspective taking, providing a more fine-grained analysis of the cognitive domain of empathy assessed in medical student empathy scales. This analysis allows us to generate new critical hypotheses about the reasons why only certain self-report empathy measures (or their subscales) are associated with physicians’ observed empathic ability.
, Ye-Jee Kim, Min-Ju Kim, Jwa Hoon Kim, Sung-Cheol Yun, Jiwon Jung, Yong Pil Chong, Sung-Han Kim, Sang-Ho Choi, Yang Soo Kim, et al.
Published: 14 September 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-002960

Abstract:
Background While some recent studies have reported the development of tuberculosis (TB) in patients exposed to immune checkpoint inhibitors (ICIs), there is limited evidence to date. Therefore, we evaluated the risk of TB in patients with cancer exposed to ICIs using the National Health Insurance claims data in South Korea. Methods Patients with diagnostic codes for non-small cell lung cancer, urothelial carcinoma or melanoma between August 2017 and June 2019 were identified. The incidence rate and standardized incidence ratio (SIR) of TB were calculated for both the ICI exposure and non-exposure groups. The risk of TB according to ICI exposure was assessed using a multivariable Cox regression model. Results During the study period, 141 550 patients with cancer and 916 new TB cases were identified. Among the 5037 patients exposed to ICIs, 20 were diagnosed with TB at a median of 2.2 months after the ICI was initiated. The crude incidence rate of TB per 100,000 person-years was 675.8 (95% CI 412.8 to 1043.8) for the ICI exposure group and 599.1 (95% CI 560.5 to 639.6) for the non-exposure group. The SIR for TB was 8.1 (95% CI 8.0 to 8.2) in the ICI exposure group. After adjusting for potential confounding factors, ICI treatment was not significantly associated with an increased risk of TB (HR: 0.73; 95% CI 0.47 to 1.14). Conclusions While the incidence of TB in cancer patients exposed to ICIs was eightfold higher than in the general population, the risk of patients with cancer developing TB did not significantly differ according to ICI exposure.
, , Masashi Shigeyasu, Nobuyuki Sakai
Published: 14 September 2021
by BMJ
BMJ Case Reports, Volume 14; https://doi.org/10.1136/bcr-2021-244950

Abstract:
The standard endovascular treatment for ruptured dissecting aneurysm is a parent artery occlusion. However, this treatment is unsuitable when the artery of the lesion gives off perforating vessels that supply blood to critical regions or when the collateral flow cannot be expected due to the sacrifice of the parent artery. Here, we present an infrequent case of ruptured dissecting aneurysm on P1 segment of the posterior cerebral artery. The aneurysm had little sac for coiling and the artery of the lesion had some perforator branches; thus, we selected the monotherapy with three overlapping low-profile visualised intraluminal support stents as radical treatment, which resulted in prompt obliteration of the aneurysm. The patient was fully recovered at 3 months after the procedure. Previous studies have reported the effectiveness of multiple stents alone for dissecting aneurysms, whereas this case showed that overlapping stents may also be effective on the P1 segment.
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