A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site

Carcinoma of unknown primary site remains a common clinical diagnosis, accounting for between 5 and 10% of all cancer patients. Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site, resulting in response rates of 0–48%. We present the results of a single centre phase II study of the use of the combination of mitomycin C (7 mg m−2 on day 1 of cycles 1, 3 and 5) cisplatin (60 mg m−2 on day 1) and continuous infusion 5-fluorouracil (300 mg m−2 daily), MCF, delivered as a 21-day cycle, in patients with carcinoma of unknown primary site. Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF. In total, 136 cycles of MCF were delivered (median of 5 cycles per patient). Toxicity was acceptable, with 19% grade 3 or 4 neutropenia, 16% grade 3 or 4 thrombocytopenia and 13% grade 3 or 4 nausea and vomiting. No cases of neutropenic sepsis were seen and there were no treatment-related deaths, however, six patients developed thrombotic complications. The overall response rate was 27% (CR 3%; PR 23%). Median time to progression was 3.4 months (95% CI 1.1–5.6 months) and median overall survival was 7.7 months (95% CI 5.7–9.8 months). Survival at 1 year was 28%, and at 2 years, 10%. MCF is a tolerable regimen with comparable toxicity, response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Hepatitis C virus notification rates in Australia are highest in socioeconomically disadvantaged areas

<div><p>Background</p><p>Poor access to health services is a significant barrier to achieving the World Health Organization’s hepatitis C virus (HCV) elimination targets. We demonstrate how geospatial analysis can be performed with commonly available data to identify areas with the greatest unmet demand for HCV services.</p><p>Methods</p><p>We performed an Australia-wide cross-sectional analysis of 2015 HCV notification rates using local government areas (LGAs) as our unit of analysis. A zero-inflated negative binomial regression was used to determine associations between notification rates and socioeconomic/demographic factors, health service and geographic remoteness area (RA) classification variables. Additionally, component scores were extracted from a principal component analysis (PCA) of the healthcare service variables to provide rankings of relative service coverage and unmet demand across Australia.</p><p>Results</p><p>Among LGAs with non-zero notifications, higher rates were associated with areas that had increased socioeconomic disadvantage, more needle and syringe services (incidence rate ratio [IRR] 1.022; 95%CI 1.001, 1.044) and more alcohol and other drug services (IRR 1.019; 1.005, 1.034). The distribution of PCA component scores indicated that per-capita healthcare service coverage was lower in areas outside of major Australian cities. Areas outside of major cities also contained 94% of LGAs in the lowest two socioeconomic quintiles, as well as 35% of HCV notifications despite only representing 29% of the population.</p><p>Conclusions</p><p>As countries aim for HCV elimination, routinely collected data can be used to identify geographical areas for priority service delivery. In Australia, the unmet demand for HCV treatment services is greatest in socioeconomically disadvantaged and non-metropolitan areas.</p></div

Quintile rank of 2015 unmet demand index by Australian Local Government Area.

<p>Quintile 1 indicates the 20% of LGAs with the least unmet demand. LGAs removed from the analysis are indicated in grey. Adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198336#pone.0198336.ref033" target="_blank">33</a>] under a CC BY license, with permission from the Commonwealth of Australia, original copyright 2016.</p

Quintile rank of 2015 notification rates by Australian Local Government Area.

<p>Quintile 1 indicates the 20% of LGAs with the lowest notifications per 100,000 population. LGAs removed from the analysis are indicated in grey. Adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198336#pone.0198336.ref033" target="_blank">33</a>] under a CC BY license, with permission from the Commonwealth of Australia, original copyright 2016.</p

Zero-inflated negative binomial regression.

<p>Zero-inflated negative binomial regression.</p

Primary services for HCV.

<p>Primary services for HCV.</p

Hepatitis C virus notification rates in Australia are highest in socioeconomically disadvantaged areas - Fig 1

<p><b>Bivariate distribution of notification rate (per 100,000 population) and remoteness areas (top left), presence of a prison (top right), state (bottom left) and IRSD quintile (bottom right).</b> The vertical axis has been cropped to 200 notifications per 100,000 population in each plot to improve readability.</p

Loadings for healthcare services variables onto the first principle component extracted from the PCA.

<p>Loadings for healthcare services variables onto the first principle component extracted from the PCA.</p