The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

BACKGROUND: Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. OBJECTIVES: To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. METHODS: Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. RESULTS: Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. CONCLUSION: Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Rapid detection of S. pyogenes and S. pneumoniae in pleural fluid for diagnosis of parapneumonic empyema.

The aim of this study was to assess the reliability of rapid antigen detection tests (RADT) for Streptococcus pyogenes (GAS) and Streptococcus pneumoniae on pleural fluid samples for diagnosis of parapneumonic effusion/empyema (PPE) and their potential for improving pathogen identification rates. Sixty-three pleural samples were included from 54 patients on which GAS and S. pneumoniae RADT (BinaxNOW), culture, 16S rRNA PCR, and S. pneumoniae-specific PCR were performed. GAS RADT showed a sensitivity of 95.2% and a specificity of 100%. Pneumococcal RADT showed a sensitivity of 100% and specificity of 88.6%. Both RADT increased the pathogen identification rate in PPE compared to culture.

HIV Pre-exposure Prophylaxis (PrEP) Care in Belgium: A mixed-methods Study on PrEP Users' Experiences and Service Delivery Preferences.

In Belgium, HIV pre-exposure prophylaxis (PrEP) services are mainly provided through specialised HIV clinics. To optimise PrEP uptake and retention in care, we require insights into users' perspectives on PrEP care. We aimed to elicit experiences with, and preferences for, PrEP service delivery among PrEP users in Belgium, including willingness to involve their family physician (FP) in PrEP care. We adopted a sequential mixed-methods design. We used a web-based longitudinal study among 326 PrEP users that consisted of two questionnaires at six-month intervals, and complemented this with 21 semi-structured interviews (September 2020-January 2022). We conducted descriptive analyses and logistic regression to examine factors associated with willingness to involve their FP in PrEP care. Interviews were analysed using thematic analysis. Survey respondents reported high satisfaction with care received in HIV clinics [median score 9 (IQR 8-10), 10='very satisfied']. Interviews revealed the importance of regular HIV/STI screening, and the expertise and stigma-free environment of HIV clinics. Yet, they also contextualised service delivery barriers reported in the questionnaire, including the burden of cost and challenges integrating PrEP visits into their private and professional lives. Although 63.8% (n = 208/326) of baseline respondents preferred attending an HIV clinic for PrEP follow-up, 51.9% (n = 108/208) of participants in the follow-up questionnaire reported to be willing to have their FP involved in PrEP care. Participants reporting trust in FPs' PrEP and sexual health expertise, or who didn't feel judged by their FP, were more likely to be willing to involve them in PrEP care. Therefore, we recommend a differentiated PrEP service delivery approach, including involving FPs, to make PrEP care more client-centred.

Clostridioides difficile recurrence in individuals with and without cancer: a Swedish population-based cohort study.

PURPOSE: Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored. METHODS: This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006-2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status. RESULTS: Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73-0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43-1.74; Cancer history: OR = 1.45, 95% CI 1.36-1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76-0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97-1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found. CONCLUSION: The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.

Clostridioides difficile infection, recurrence and the associated healthcare consumption in Sweden between 2006 and 2019: a population-based cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). METHODS: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. RESULTS: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40-18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16-9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84-4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31-3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12-1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68-7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07-8.26). CONCLUSION: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI.

Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

INTRODUCTION: Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). MATERIAL AND METHODS: This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37-1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88-2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose-response analysis. CONCLUSIONS: The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression.

ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

A public health value-based healthcare paradigm for HIV.

BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.

A treatment recommender clinical decision support system for personalized medicine: method development and proof-of-concept for drug resistant tuberculosis.

BACKGROUND: Personalized medicine tailors care based on the patient's or pathogen's genotypic and phenotypic characteristics. An automated Clinical Decision Support System (CDSS) could help translate the genotypic and phenotypic characteristics into optimal treatment and thus facilitate implementation of individualized treatment by less experienced physicians. METHODS: We developed a hybrid knowledge- and data-driven treatment recommender CDSS. Stakeholders and experts first define the knowledge base by identifying and quantifying drug and regimen features for the prototype model input. In an iterative manner, feedback from experts is harvested to generate model training datasets, machine learning methods are applied to identify complex relations and patterns in the data, and model performance is assessed by estimating the precision at one, mean reciprocal rank and mean average precision. Once the model performance no longer iteratively increases, a validation dataset is used to assess model overfitting. RESULTS: We applied the novel methodology to develop a treatment recommender CDSS for individualized treatment of drug resistant tuberculosis as a proof of concept. Using input from stakeholders and three rounds of expert feedback on a dataset of 355 patients with 129 unique drug resistance profiles, the model had a 95% precision at 1 indicating that the highest ranked treatment regimen was considered appropriate by the experts in 95% of cases. Use of a validation data set however suggested substantial model overfitting, with a reduction in precision at 1 to 78%. CONCLUSION: Our novel and flexible hybrid knowledge- and data-driven treatment recommender CDSS is a first step towards the automation of individualized treatment for personalized medicine. Further research should assess its value in fields other than drug resistant tuberculosis, develop solid statistical approaches to assess model performance, and evaluate their accuracy in real-life clinical settings.

Etiology of Early-Onset Neonatal Sepsis and Antibiotic Resistance in Bukavu, Democratic Republic of the Congo.

BACKGROUND: The Democratic Republic of the Congo (DRC) has one of the highest neonatal death rates (between 14% and 28%) in the world. In the DRC, neonatal sepsis causes 15.6% of this mortality, but data on the bacterial etiology and associated drug susceptibility are lacking. METHODS: Hemocultures of 150 neonates with possible early-onset neonatal sepsis (pEOS) were obtained at the Hôpital Provincial Général de Référence de Bukavu (Bukavu, DRC). The newborns with pEOS received an empirical first-line antimicrobial treatment (ampicillin, cefotaxime, and gentamicin) based on the synopsis of international guidelines for the management of EOS that are in line with World Health Organization (WHO) recommendations. Isolates were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrophotometry. Antibiotic resistance was assessed using the disk diffusion method. RESULTS: Fifty strains were obtained from 48 patients and identified. The 3 most prevalent species were Enterobacter cloacae complex (42%), Klebsiella pneumoniae (18%), and Serratia marcescens (12%). Enterobacter cloacae isolates were resistant to all first-line antibiotics. All K. pneumoniae and S. marcescens isolates were resistant to ampicillin, and the majority of the K. pneumoniae and half of the S. marcescens isolates were resistant to both cefotaxime and gentamicin. All E. cloacae complex strains, 89% of K. pneumoniae, and half of S. marcescens had an extended-spectrum ß-lactamase phenotype. CONCLUSIONS: The most prevalent pathogens causing EOS in Bukavu were E. cloacae complex, K. pneumoniae, and S. marcescens. Most of these isolates were resistant to the WHO-recommended antibiotics.

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Combined oropharyngeal/nasal swab is equivalent to nasopharyngeal sampling for SARS-CoV-2 diagnostic PCR.

BACKGROUND: Early 2020, a COVID-19 epidemic became a public health emergency of international concern. To address this pandemic broad testing with an easy, comfortable and reliable testing method is of utmost concern. Nasopharyngeal (NP) swab sampling is the reference method though hampered by international supply shortages. A new oropharyngeal/nasal (OP/N) sampling method was investigated using the more readily available throat swab. RESULTS: 35 patients were diagnosed with SARS-CoV-2 by means of either NP or OP/N sampling. The paired swabs were both positive in 31 patients. The one patient who tested negative on both NP and OP/N swab on admission, was ultimately diagnosed on bronchoalveolar lavage fluid. A strong correlation was found between the viral RNA loads of the paired swabs (r = 0.76; P < 0.05). The sensitivity of NP and OP/N analysis in hospitalized patients (n = 28) was 89.3% and 92.7% respectively. CONCLUSIONS: This study demonstrates equivalence of NP and OP/N sampling for detection of SARS-CoV-2 by means of rRT-PCR. Sensitivity of both NP and OP/N sampling is very high in hospitalized patients.

Gaps in HIV Testing and Treatment Among Female Sex Workers in Lae and Mt. Hagen, Papua New Guinea.

We conducted biobehavioral surveys among female sex workers (FSW) in Lae and Mt. Hagen, Papua New Guinea (January-December 2017). Respondent-driven sampling was used to recruit FSW aged ≥ 12 years, who were assigned female sex at birth, who spoke English or Tok Pisin, and who sold or exchanged sex for money, goods, or services in the last 6 months. When adjusted for viral suppression, 48.9% of FSW Lae and 61.9% in Mt. Hagen were aware of their HIV positive status. Of these women, 95.3% in Lae and 98.9% in Mt. Hagen were on antiretroviral therapy, and of these, 83.5% in Lae and 87.0% in Mt. Hagen had suppressed viral load. Renewed efforts are needed to increase HIV testing among FSW and provide support to FSW on treatment in both cities to attain viral suppression.

Prediagnostic use of estrogen-only therapy is associated with improved colorectal cancer survival in menopausal women: a Swedish population-based cohort study.

BACKGROUND: Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. METHODS: This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. RESULTS: Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44-0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59-0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02-1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06-2.44) in older women, but no association was shown for all-cause mortality. CONCLUSIONS: Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear.

Evaluation of a turbidimetric C-reactive protein assay to monitor early-onset neonatal sepsis in South Kivu (Democratic Republic of the Congo).

OBJECTIVES: Neonatal sepsis, a condition defined as bacteremia within the first month of life accompanied by signs of systemic infection, is the most preventable cause of infant mortality in sub-Saharan Africa. Despite the development of new infection markers, C-reactive protein (CRP) is the most extensively studied acute phase reactant so far and the preferred index in many neonatal intensive care units (NICUs). The aim of the present study was to evaluate an affordable, non-commercial turbidimetric CRP assay for monitoring early-onset neonatal sepsis (EOS). METHODS: A total of 148 neonates admitted at the NICU of the Hôpital Provincial Général de Référence de Bukavu to diagnose and to monitor EOS were enrolled in the study. CRP was assayed using a functional turbidimetric assay based on the interaction of CRP with phosphocholine containing particles (Intralipid®). RESULTS: In total, 62/148 (41.9%) cases were identified as blood culture-proven EOS. Different serum CRP slopes were observed among the different birth weight categories. Moreover, the serum (CRP 48 h-CRP 12 h) difference and the birth weight predicted the outcome of these septic newborns. CONCLUSIONS: Our turbidimetric CRP assay is a potential novel tool that can be used in the management of EOS in sub-Saharan Africa. The simplicity of the assay and the extremely low price make the CRP method very well suited for developing countries.

Prediction of hospital bed capacity during the COVID- 19 pandemic.

BACKGROUND: Prediction of the necessary capacity of beds by ward type (e.g. ICU) is essential for planning purposes during epidemics, such as the COVID- 19 pandemic. The COVID- 19 taskforce within the Ghent University hospital made use of ten-day forecasts on the required number of beds for COVID- 19 patients across different wards. METHODS: The planning tool combined a Poisson model for the number of newly admitted patients on each day with a multistate model for the transitions of admitted patients to the different wards, discharge or death. These models were used to simulate the required capacity of beds by ward type over the next 10 days, along with worst-case and best-case bounds. RESULTS: Overall, the models resulted in good predictions of the required number of beds across different hospital wards. Short-term predictions were especially accurate as these are less sensitive to sudden changes in number of beds on a given ward (e.g. due to referrals). Code snippets and details on the set-up are provided to guide the reader to apply the planning tool on one's own hospital data. CONCLUSIONS: We were able to achieve a fast setup of a planning tool useful within the COVID- 19 pandemic, with a fair prediction on the needed capacity by ward type. This methodology can also be applied for other epidemics.

Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study.

Although menopausal hormone therapy (MHT) seemingly increases the risk of ovarian cancer, evidence is insufficient whether the risk varies between various MHT formulations, regimens and administration modes. With the aim of filling these knowledge gaps, we investigated the effect of different MHT treatment options on the risk of ovarian cancer. This prospective Swedish population-based matched-cohort study included all women ≥40 years having used systemic MHT between 2005 and 2012 (288,950 ever-users), group-level matched (1:3) to 866,546 nonusers. MHT use was ascertained from the Swedish Prescribed Drug Registry and data was linked to several national health data registries. Multivariable conditional logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for parity, and comorbidities. Current EP-MHT use was associated with a modestly increased risk of ovarian cancer (OR = 1.38, 95% CI 1.18-1.62), while no consistent risk was found among past users (OR = 1.00, 95% CI 0.84-1.18). Current continuous testosterone derived (OR = 1.50, 95% CI 1.15-1.96) regimens increased the risk whereas progesterone derived (OR = 1.48, 95% CI 1.00-2.21) regimens increased the risk marginally. Nonsignificant positive associations were observed for sequential regimens (OR = 1.87, 95% CI 0.70-5.08; OR = 1.54, 95% CI 0.96-2.47, respectively). An inverse relationship was observed for all E-MHT use (OR = 0.25, 95% CI 0.22-0.29), but this association might partly be explained by underreporting of oophorectomies or tubal ligations. Current cutaneous EP-MHT (OR = 1.28, 95% CI 0.81-2.02) suggested a possibly lower risk than oral MHT (OR = 1.48, 95% CI 1.25-1.75). In conclusion EP-MHT, notably continuous regimens, were associated with a modestly increased risk of ovarian cancer. The role of E-MHT requires further clarification.

Antibiotic use and risk of colorectal cancer: a systematic review and dose-response meta-analysis.

BACKGROUND: It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present. DESIGN: Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose-response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models. RESULTS: Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05-1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26-2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93-1.32). The dose-response analysis did not provide strong evidence of any particular dose-response association, and the risk patterns were rather similar for colon and rectal cancer. DISCUSSION: The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug-microbiome interactions.

Antibiotic use and the risk of breast cancer: A systematic review and dose-response meta-analysis.

OBJECTIVE: Oral antibiotics are posed as a possible risk factor for breast cancer. Evidence is insufficient to determine whether the choice of antibiotic class could effect this potential association, and non-linearity has not been studied. We aimed to fill these important knowledge gaps. METHODS: PubMed, Web of Science, Embase and a trial registry were searched from inception until January 2020, without any restrictions. Additionally, extensive manual searches were undertaken. Random-effects meta-analyses provided pooled risk estimates with 95 % confidence intervals (CI). Dose-response analyses modeling the relationship between number of antibiotic prescriptions and breast cancer risk were extended to non-linear models. Heterogeneity, publication bias and small-study effects were assessed. RESULTS: Of 7805 identified publications ten were eligible, including 3,719,383 individuals and 84,485 breast cancer cases. The pooled breast cancer risk was modestly increased among individuals who ever used antibiotics (relative risk RR = 1.18, 95 %CI 1.08-1.29), also after excluding the last year prior diagnosis. This excess risk was seen among penicillin (RR = 1.09, 95 %CI 1.01-1.18), tetracycline (RR = 1.13, 95 %CI 1.04-1.24) and nitrofuran users (RR = 1.26, 95 %CI 1.05-1.52), whilst nitroimidazole and metronidazole use (RR = 1.05, 95 %CI 1.00-1.11) indicated for marginal association. No apparent association was found for other antibiotics. Data suggested for a non-linear dose-dependent relationship, with a seemingly protective effect after at least 35 prescriptions. However, these findings might partly be explained by limited power of dose-response analyses. CONCLUSIONS: The association of antibiotics with breast cancer risk appears to differ between the various antibiotic classes. Whether this association is causal remains unclear, requiring further clarification and mechanistic studies.

One size does not fit all: HIV prevalence and correlates of risk for men who have sex with men, transgender women in multiple cities in Papua New Guinea.

BACKGROUND: Biobehavioral data about men who have sex with men (MSM) and transgender women (TGW) in Papua New Guinea (PNG) are limited to those who sell sex. Information about those MSM and TGW who do not sell sex is necessary to guide HIV prevention and treatment efforts. METHODS: We conducted respondent-driven sampling (RDS) surveys among MSM and TGW in Port Moresby, Lae, and Mt. Hagen, PNG from in 2016 and 2017. Eligibility criteria was: aged > 12 years, born male, could speak English or Tok Pisin and had oral or anal sex with another person born male in the past 6 months. Participants were interviewed face-to-face and offered rapid HIV testing. Weighted data analysis was conducted using RDS-Analyst (v. 0.62). RESULTS: We enrolled 400 participants in Port Moresby, 352 in Lae, and 111 in Mt. Hagen. In the last six months, 73.2% of MSM/TGW in Port Moresby, 77.9% in Lae, and 75.9% in Mt. Hagen, had a concurrent sexual partnership. Upwards of 70% of MSM/TGW in all three cities had sex with a woman in the same period. Less than half of MSM/TGW had ever tested for HIV. HIV prevalence among MSM/TGW was 8.5% in Port Moresby and 6.9% in Lae. Among participants in Mt. Hagen it was 1.3%. HIV was associated with not having sex with a woman in the last six months and sexually transmitted disease symptoms in the last 12 months in Port Moresby and Lae. In Port Moresby, it was also associated with an uncut foreskin, and in Lae with earning income in the formal sector and being unable to rely on other MSM or TGW to accompany them to healthcare services. CONCLUSIONS: The large proportion of MSM and TGW with concurrent sexual partnerships, combined with the low testing coverage, indicates strong potential for the spread of HIV. The different correlates of HIV in Port Moresby and Lae highlight the importance of conducting surveys in multiple locations and using data to develop locally appropriate interventions even within a country.