Healthcare workers acquired COVID-19 disease from patients? An investigation by phylogenomics.

The increasing number of coronavirus disease 2019 (COVID-19) cases in the community has posed a significant epidemic pressure on healthcare settings. When healthcare workers (HCWs) acquire COVID-19, contact tracing and epidemiological investigation might not be adequate for determining the source of transmission. Here, we report a phylogenetic investigation involving two infected HCWs and nine patients to determine whether patient-to-HCW transmission had occurred in a hospital without a previous COVID-19 outbreak. This is the first study to apply phylogenomics to investigate suspected nosocomial transmission in a region with low prevalence of COVID-19. Our results do not support the occurrence of direct patient-to-HCW transmission.

Relationship of Urethral Dose and Genitourinary Toxicity Among Patients Receiving Vaginal High Dose Rate Interstitial Brachytherapy.

AIMS: Interstitial brachytherapy (ISBT) plays an important role in the management of locally advanced gynaecological malignancies. However, the relationship between urinary toxicity and dose to the urethra is not well understood. We sought to evaluate the correlation between urethral dose and the incidence of genitourinary complications among patients undergoing vaginal high dose rate ISBT. MATERIALS AND METHODS: Eighty-three patients treated with ISBT between August 2014 and April 2018 were retrospectively reviewed. CTCAE version 5.0 was used to grade toxicity. Individual treatment plans were evaluated to collect dose parameters. Urethral contours were added to the structure sets using a uniform 1 cm diameter brush and minimum doses to the hottest 0.1, 0.2 and 0.5 cm3 (D0.1cm3, D0.2cm3 and D0.5cm3) of the urethra were obtained. Total (ISBT ± external beam radiotherapy) equivalent doses in 2 Gy fractions (EQD2) received by the targets and organs at risk were calculated. Numerical counts (%) and medians (interquartile range) were used to characterise the data. Fisher's exact and the Mann-Whitney-Wilcox tests were used as appropriate. Receiver operator curve analysis was used to define the urethral threshold dose that correlated to genitourinary toxicity. RESULTS: The median age and follow-up times were 67 years (59-75) and 25 months (16-37), respectively. Patients had predominantly primary endometrial (49%) and vaginal (37%) cancer, with four (5%) patients with metastatic rectal cancer to the vagina. Twenty-four of 79 (30%) patients experienced acute genitourinary toxicity and 34 of 71 (48%) experienced late genitourinary toxicity. In both analyses, the median urethral dose was significantly higher among those with toxicity. Receiver operator curve analysis indicated that D0.1cm3, D0.2cm3 and D0.5cm3 of the urethra were associated with the development of toxicity at doses >78, >71 and >62 Gy, respectively. CONCLUSION: Urethral dose seems to predict genitourinary toxicity in ISBT of vaginal tumours. Further study with an expanded cohort and longer follow-up is warranted.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Diagnostic stewardship programme for urine culture: impact on antimicrobial prescription in a multi-centre cohort.

BACKGROUND: Restricting urine culture to patients with genuine urinary tract infection (UTI) reduces excessive antimicrobial prescription for asymptomatic bacteriuria. AIM: To evaluate the impact of urine culture diagnostic stewardship on antimicrobial consumption. METHODS: This quasi-study involved two general hospitals and 10 community clinics. In the pre-intervention (control) phase (25th November 2018-2nd February 2019), microscopy and culture results of all urine specimens were reported. In the post-intervention (study) phase (25th November 2019-2nd February 2020), urine cultures were processed and reported only if at least one of the following criteria were met: presence of white blood cells or bacteria on microscopy; patient from obstetrics, urology, paediatrics, oncology or renal transplant ward; specimen labelled as 'pregnancy', 'urological procedure', 'renal transplant' or 'neutropenic'; and ureteric, nephrostomy or suprapubic urine. For urine samples that did not fulfil these criteria, the microscopy results and a rejection comment were reported. FINDINGS: In total, 12,282 urine specimens were included in the intervention phase. Of these, 4757 (38.7%) specimens did not fulfil the screening criteria, and the microscopy result and a rejection comment were reported. One hundred and sixty-three (3.4%) of these non-reported urine cultures yielded significant bacterial growth, and the majority were Escherichia coli (N=58, 35.6%). Diagnostic stewardship was independently associated with lower antimicrobial consumption [adjusted odds ratio 0.76, 95% confidence interval (CI) 0.70-0.83, P<0.001] on multi-variable logistic regression across all healthcare settings. Diagnostic stewardship had no effect on patient mortality (adjusted hazard ratio=0.95, 95% CI 0.89-1.01, P=0.08). No patients with unreported urine culture developed bacteraemia from untreated UTI. CONCLUSION: Diagnostic stewardship of urine culture safely reduced excessive antimicrobial prescription for asymptomatic bacteriuria.

Contemporary endovascular management of splenic vascular pathologies.

The spleen is a commonly injured organ and the splenic vasculature is also susceptible to inflammation and trauma, often resulting in aneurysm formation. Splenic artery aneurysms carry a high risk of rupture and are associated with high mortality and morbidity. Due to the advances in endovascular techniques and devices, endovascular management of splenic vascular pathologies is now considered a first-line strategy. Endovascular embolisation and advance techniques including balloon- or stent-assisted coil embolisation enables minimally invasive management option while preserving splenic function.

Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

Tablet-based electroencephalography diagnostics for patients with epilepsy in the West African Republic of Guinea.

BACKGROUND AND PURPOSE: Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. METHODS: Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. RESULTS: There were 149 participants (41% female; median age 17.9 years; 66.6% ≤21 years of age; mean seizures per month 5.7 ± SD 15.5). The mean duration of EEG1 was 53 ± 12.3 min and that of EEG2 was 29.6 ± 12.8 min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n = 53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. CONCLUSIONS: Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

R0 Resection Margin, A New Quality Measure in the Era of National Bowel Screening?

Aims To determine the completeness of polyp resection (i.e. achieving an R0 margin) and its relation with Endoscopists, histopathologist, size, location and technique of polypectomy in an NSS cohort. The definition of R0 margin is complete macroscopic resection with a negative microscopic margin at polypectomy. Method NCCS (National Colon Cancer Screening) colonoscopies are offered to bowel cancer screening patients after a positive faecal immunochemical test (FIT) test in a Joint Advisory Group (JAG) accredited Gastrointestinal Endoscopy centre. We histologically evaluated the polyp margins for complete resection, which was defined as the absence of adenomatous or hyperplastic tissue in the resected polyp margins in a cohort of faecal immunochemical test positive patients. Results A total of 186 consecutive NCCS colonoscopies out of a total of 542 performed between 2013 and 2017 were included in this study. Of the polyps excised 152(27%) had a R0 margin histologically, and 30(5%) had involvement of the margin. Surprisingly in 373(67%) of polyps pathologists were unable to assess the margin. Conclusion Achieving an R0 margin should be a key performance indicator for endoscopists performing polypectomy. At the same time more studies on polyp margins are recommended.

Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

A randomised phase II trial of three dosing regimens of radium-223 in patients with bone metastatic castration-resistant prostate cancer.

BACKGROUND: Radium-223 prolongs overall survival and delays symptomatic skeletal events (SSEs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. The approved radium-223 regimen is 55 kBq/kg every 4 weeks (q4w) for six cycles (standard dose). We investigated different radium-223 regimens in patients with mCRPC. PATIENTS AND METHODS: Patients were randomised 1 : 1 : 1 to radium-223 standard-dose, high-dose (88 kBq/kg q4w for six cycles) or extended-schedule arms (55 kBq/kg q4w for 12 cycles). The primary end point, SSE-free survival (SSE-FS), was compared in patients treated with a high- versus standard-dose regimen, or with a standard dose in an extended (>6 to 12 cycles) versus standard schedule (six cycles). RESULTS: A total of 391 patients were randomised; baseline characteristics were balanced between arms. On-treatment SSEs developed in 37/130 (28%), 42/130 (32%) and 48/131 (37%) patients in the standard-dose, high-dose and extended-schedule arms, respectively. There was no statistically significant difference in SSE-FS in the high- versus standard-dose arms [median 12.9 months versus 12.3 months; hazard ratio (HR) 1.06, 80% confidence interval (CI) 0.88-1.27, P = 0.70], and in the extended- versus standard-schedule arms (median 10.8 months versus 13.2 months; HR 1.26, 80% CI 0.94-1.69, P = 0.31). Overall survival in the three treatment arms was similar. As many as 370 (95%) patients received treatment (median of six cycles) in each arm. Grade ≥3 treatment-emergent adverse events (TEAEs) affected 34% of patients in the standard-dose, 48% in the high-dose and 53% in the extended-schedule arm, causing permanent discontinuation in 9%, 16% and 17% of patients, respectively. CONCLUSION: Radium-223 high-dose or extended-schedule regimens resulted in no change in SSE-FS or other efficacy end points and were associated with more grade ≥3 TEAEs. The extended-schedule regimen (beyond six doses) could not be implemented in a large proportion of patients due to disease progression. Therefore, the standard-dose schedule remains one of the standard therapies for patients with symptomatic mCRPC. TRIAL REGISTRATION: ClinicalTrials.govNCT02023697.

Salvage Re-irradiation With Single-modality Interstitial Brachytherapy for the Treatment of Recurrent Gynaecological Tumours in the Pelvis: A Multi-institutional Study.

AIMS: Recurrent gynaecological tumours can cause significant morbidity with limited salvage options. This study investigates the strategy of salvage single-modality interstitial brachytherapy (SM-ISBT) for recurrent gynaecological pelvic cancer at two specialised ISBT centres. MATERIALS AND METHODS: Patients who had received salvage SM-ISBT for pelvic recurrence of gynaecological cancers from September 2008 to January 2017 were included. None had distant metastasis at the time of recurrence. Local control, progression-free and overall survival and long-term toxicities were evaluated. RESULTS: Twenty-six patients with a median follow-up of 24 months (range 2.5-106.3 months) after SM-ISBT were included. Primary cancer sites were endometrium (20), cervix (4), vulva (1) and vagina (1). All patients had prior whole-pelvic external beam irradiation and 16 had prior brachytherapy. The median disease-free survival prior to SM-ISBT was 20.3 months (interquartile range 9.9-30.5). SM-ISBT was delivered with high dose rate technique over three to six fractions. The median high-risk clinical target volume was 34.6 cm3, with a median D90 of 29.1 Gy (range 16.1-64.6). The median bladder, rectum and sigmoid D2cm3 were 15.5, 18.7 and 3.7 Gy, respectively. After SM-ISBT, complete and partial responses were achieved in 17 (64%) and 5 (19%) patients, respectively. Two (7.4%) patients had grade 3 toxicities (both vaginal stenosis), with no grade 4 complications. Eighteen patients (69%) recurred, including local, regional and metastatic in 14 (54%), 8 (30%) and 5 (19%) patients, respectively. Two-year local control, progression-free survival and overall survival were 50, 38 and 78%, respectively. In follow-up, 12 patients (46%) remained in local control. CONCLUSIONS: Salvage SM-ISBT re-irradiation for pelvic recurrence of gynaecological malignancies was feasible and safe. With limited salvage options, the local control obtained in more than a quarter of patients seems reasonable. Further efforts are needed to establish a consensus about the optimal patient selection, dose fractionation, implant technique and combination with systemic therapies.

Negative pressure wound therapy in elective stoma reversal surgery: results of a UK district general hospital pilot.

The role of negative pressure wound therapy in stoma reversal surgery remains unknown. To evaluate this, a retrospective, non-randomized, single-institution, pilot study was conducted. Surgeon preference determined type of wound closure and application of the single-brand negative wound pressure device. No patient in the intervention group suffered wound complications, but five of the thirty-six patients in the control group suffered surgical site infection-related complications. Primary closure and negative pressure wound therapy use decreases wound complications in stoma reversal surgery, thereby alleviating the wound-management burden in hospitals and in the community. This has cost-saving implications, but further studies are needed.

Novel tyrosyl-DNA phosphodiesterase 1 inhibitors enhance the therapeutic impact of topoteсan on in vivo tumor models.

The druggability of the tyrosyl-DNA phosphodiesterase 1 (Tdp1) enzyme was investigated in conjunction with topoisomerase 1 inhibition. A novel class of thiazole, aminothiazole and hydrazonothiazole usnic acid derivatives was synthesized and evaluated as Tdp1 inhibitors and their ability to sensitize tumors to topotecan, a topoisomerase inhibitor in clinical use. Of all the compounds tested, four hydrazinothiazole derivatives, 20c, 20d, 20h and 20i, inhibited the enzyme in the nanomolar range. The activity of the compounds was verified by affinity experiments as well as supported by molecular modelling. The most effective Tdp1 inhibitor, 20d, was ton-toxic and increased the effect of topotecan both in vitro and in vivo in the Lewis lung carcinoma model. Furthermore, 20d showed significant increase in the antitumor and antimetastatic effect of topotecan in mice. The results presented here justify compound 20d to be considered as a drug lead for antitumor therapy.

Risk factors associated with 1-year mortality among patients with HIV-associated tuberculosis in areas with intermediate tuberculosis burden and low HIV prevalence.

INTRODUCTION: Data are limited regarding risk factors for mortality among patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) in areas with low HIV prevalence and intermediate TB burden, such as the Western Pacific region. This study aimed to assess such risk factors in Hong Kong, which has an intermediate TB burden and low HIV prevalence. METHODS: We conducted a retrospective cohort analysis of adult patients reported to the Hong Kong TB-HIV Registry between 2006 and 2015. Baseline characteristics were compared with Kaplan-Meier estimates. Cox proportional hazards regression modelling was used to identify factors associated with mortality. RESULTS: Of 299 patients studied, 21 (7.0%) died within 12 months of anti-TB treatment (median [interquartile range], 7.5 [3.8-10] months). The median age of death was 54 (interquartile range, 40.5-75.0) years. The cause of death was TB in five and unrelated to TB in the remaining 16. Cox proportional hazards regression showed that older age (adjusted hazard ratio=4.5; 95% confidence interval [CI]=1.4-14.9), history of drug addiction (4.6; 95% CI=1.6-13.0), and low baseline CD4 cell count of <50/µL (2.9; 95% CI=1.1-7.7) were independent risk factors for death within 12 months. CONCLUSION: This study complements previous studies by providing information regarding risk factors associated with mortality among patients with HIV-associated TB in areas with intermediate TB burden and low HIV prevalence. The results from our study may guide targeted measures to improve survival in other areas with intermediate TB burden and low HIV prevalence, such as the Western Pacific region.