Maintaining surgical care delivery during the COVID-19 pandemic: A comparative cohort study at a tertiary gynecological cancer centre

BackgroundSurgery is the cornerstone of gynecological cancer management, but inpatient treatment may expose both patients and healthcare staff to COVID-19 infections. Plans to mitigate the impact of the COVID-19 pandemic have been implemented widely, but few studies have evaluated the effectiveness of these plans in maintaining safe surgical care delivery.AimTo evaluate the effects of mitigating plans implemented on the delivery of gynecological cancer surgery during the COVID-19 pandemic.MethodsA comparative cohort study of patients treated in a high-volume tertiary gyneoncological centre in the United Kingdom. Prospectively-recorded consecutive operations performed and early peri-operative outcomes during the same calendar periods (January–August) in 2019 and 2020 were compared.ResultsIn total, 585 operations were performed (296 in 2019; 289 in 2020). There was no significant difference in patient demographics. Types of surgery performed were different (p = 0.034), with fewer cytoreductive surgeries for ovarian cancer and laparoscopic procedures (p = 0.002) in 2020. There was no difference in intra-operative complication rates, critical care admission rates or length of stay. One patient had confirmed COVID-19 infection (0.4%). The 30-day post-operative complication rates were significantly higher in 2020 than in 2019 (58 [20.1%] versus 32 [10.8%]; p = 0.002) for both minor and major complications. This increase, primarily from March 2020 onwards, coincided with the first peak of the COVID-19 pandemic in the UK.ConclusionsMaintaining surgical throughput with meticulous and timely planning is feasible during the COVID-19 pandemic but this was associated with an increase in post-operative complications due to a multitude of reasons.     

Atazanavir trough plasma concentration monitoring in a cohort of HIV-1-positive individuals receiving highly active antiretroviral therapy

OBJECTIVES: Atazanavir is a recently approved HIV protease inhibitor (PI). As with other PIs, careful attention to potential pharmacokinetic drug interactions in clinical practice is necessary. The aim of this study was to assess the clinical associations with plasma atazanavir concentrations in HIV-positive individuals. METHODS: Individuals established on an atazanavir-containing regimen, completed an interviewer-administered questionnaire recording atazanavir dosing characteristics, concomitant medication use and adherence. After completion, plasma atazanavir concentrations were measured. RESULTS: Of 100 individuals, mean trough plasma atazanavir concentrations (mug/L) were 282 (95% CI 95-468, n = 19) and 774 (95% CI 646-902, n = 81) in those on non- and ritonavir-boosted atazanavir regimens, respectively. Eighty-five individuals had HIV RNA <50 copies/mL. Seven individuals had atazanavir plasma concentrations below the assay limit of detection (<50 microg/L), all of whom had undetectable plasma HIV RNA. In a multivariate analysis, nevirapine use was associated with significantly lower trough atazanavir concentrations (P = 0.011) and lopinavir/ritonavir use with higher trough atazanavir concentrations (P = 0.032). Dosing characteristics (including food taken), concomitant medications (including drugs used for dyspepsia) and HIV RNA were not significantly associated with trough atazanavir concentrations. CONCLUSIONS: In this cohort, despite the wide inter-individual variability of atazanavir trough concentrations, no significant association with dosing characteristics, concomitant medication (with the exception of nevirapine and lopinavir/ritonavir) or virological response was observed. Further work is needed to assess the optimal dosing regimen when using atazanavir with nevirapine.     

Early syphilis presenting as a painful polyradiculopathy in an HIV positive individual

Neurosyphilis and neurological complications from syphilis may be commoner in HIV disease. With outbreaks of early syphilis in HIV positive individuals being observed over recent years, rare neurological manifestations of secondary syphilis will be observed more commonly. We describe a case of an HIV positive individual whose first presenting feature of early syphilis was a polyradiculopathy.     

Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians

A recent genome-wide association study (GWAS) conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC) identified a number of putative MS susceptibility genes. Here we have performed a replication study in 1134 Australian MS cases and 1265 controls for 17 risk-associated single nucleotide polymorphisms (SNPs) reported by the IMSGC. Of 16 SNPs that passed quality control filters, four, each corresponding to a different non-human leukocyte antigen (HLA) gene, were associated with disease susceptibility: KIAA0350 (rs6498169) P=0.001, IL2RA (rs2104286) P=0.033, RPL5 (rs6604026) P=0.041 and CD58 (rs12044852) P=0.042. There was no association (P=0.58) between rs6897932 in the IL7R gene and the risk of MS. No interactions were detected between the replicated IMSGC SNPs and HLA-DRB1*15, gender, disease course, disease progression or age-at-onset. We used a novel Bayesian approach to estimate the extent to which our data increased or decreased evidence for association with the six most-associated IMSGC loci. These analyses indicated that even modest P-values, such as those reported here, can contribute markedly to the posterior probability of 'true' association in replication studies. In conclusion, these data provide support for the involvement of four non-HLA genes in the pathogenesis of MS, and combined with previous data, increase to genome-wide significance (P=3 x 10(-8)) evidence of an association between KIAA0350 and risk of disease.     

Early mortality among aboriginal and non-aboriginal women who had a preterm birth in Western Australia: A population-based cohort study

Background

Having a preterm (<37 weeks' gestation) birth may increase a woman's risk of early mortality. Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have higher preterm birth and mortality rates compared with other Australian women.

Objectives

We investigated whether a history of having a preterm birth was associated with early mortality in women and whether these associations differed by Aboriginal status.

Methods

This retrospective cohort study used population-based perinatal records of women who had a singleton birth between 1980 and 2015 in Western Australia linked to Death Registry data until June 2018. The primary and secondary outcomes were all-cause and cause-specific mortality respectively. After stratification by Aboriginal status, rate differences were calculated, and Cox proportional hazard regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cause-specific mortality.

Results

There were 20,244 Aboriginal mothers (1349 deaths) and 457,357 non-Aboriginal mothers (7646 deaths) with 8.6 million person-years of follow-up. The all-cause mortality rates for Aboriginal mothers who had preterm births and term births were 529.5 and 344.0 (rate difference 185.5, 95% CI 135.5, 238.5) per 100,000 person-years respectively. Among non-Aboriginal mothers, the corresponding figures were 125.5 and 88.6 (rate difference 37.0, 95% CI 29.4, 44.9) per 100,000 person-years. The HR for all-cause mortality for Aboriginal and non-Aboriginal mothers associated with preterm birth were 1.48 (95% CI 1.32, 1.66) and 1.35 (95% CI 1.26, 1.44), respectively, compared with term birth. Compared with mothers who had term births, mothers of preterm births had higher relative risks of mortality from diabetes, cardiovascular, digestive and external causes.

Conclusions

Both Aboriginal and non-Aboriginal women who had a preterm birth had a moderately increased risk of mortality up to 38 years after the birth, reinforcing the importance of primary prevention and ongoing screening.