A revised prediction model for natural conception Bensdorp, Alexandra J; van der Steeg, Jan Willem; Steures, Pieternel ...
Reproductive biomedicine online,
06/2017, Volume:
34, Issue:
6
Journal Article
Peer reviewed
Open access
Highlights • The Hunault model is the standard prediction model for natural conception. • This model can be revised by including additional predictors. • The revised model is applicable to a broader ...population. • The revised model needs to be externally validated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
The transmission of direct-acting antiviral resistance-associated substitutions (RAS) could hamper hepatitis C virus (HCV) cure rates and elimination efforts. A phylogenetic analysis of 87 ...men who have sex with men recently infected with HCV genotype 1a placed one-third (28/87) in a large cluster, in which 96% harbored NS5A M28V RAS.
The risk of venous thrombotic events is elevated in people with HIV, but overall risk estimates and estimates specific to immune status and antiretroviral medication remain i mprecise. In this study, ...we aimed to estimate these parameters in a large cohort of people with HIV in the Netherlands.
In this retrospective cohort study, we used the Dutch ATHENA cohort to estimate crude, age and sex standardised, and risk period-specific incidences of a first venous thrombotic event in people with HIV aged 18 years or older attending 12 HIV treatment centres in the Netherlands. Crude and standardised incidences were compared with European population-level studies of venous thrombotic events. We used time-updated Cox regression to estimate the risk of a first venous thrombotic event in association with HIV-specific factors (CD4 cell count, viral load, recent opportunistic infections, antiretroviral medication use) adjusted for traditional risk factors for venous thrombotic events.
With data collected from Jan 1, 2003, to April 1, 2015, our study cohort included 14 389 people with HIV and 99 762 person-years of follow-up, with a median follow-up of 7·2 years (IQR 3·3-11·1). During this period, 232 first venous thrombotic events occurred, yielding a crude incidence of 2·33 events per 1000 person-years (95% CI 2·04-2·64) and an incidence standardised for age and sex of 2·50 events per 1000 (2·18-2·82). CD4 counts less than 200 cells per μL were independently associated with higher risk of a venous thrombotic event: adjusted hazard ratio (aHR) 3·40 (95% CI 2·28-5·08) relative to counts of 500 cells per μL. A high viral load (aHR 3·15, 95% CI 2·00-5·02; >100 000 copies per mL vs <50 copies per mL) and current or recent opportunistic adverse events (2·80, 1·77-4·44) were also independently associated with higher risk of a venous thrombotic event. There were no associations between any specific antiretroviral drugs and risk of a venous thrombotic event. Rates associated with pregnancy (9·4, 95% CI 4·6-17·3), malignancy (16·7, 10·6-25·1), and hospitalisation (24·4, 19·1-30·6) were lower than primary thromboprophylaxis thresholds suggested by the respective guidelines.
Our findings support neither prescribing primary outpatient thromboprophylaxis nor avoiding any type of antiretroviral medication in people with HIV at high risk of a venous thrombotic event.
Dutch Ministry of Health, Welfare and Sport.
Background. The use of antiretroviral therapy during pregnancy is important for control of maternal human immunodeficiency virus (HIV) disease and the prevention of perinatal HIV transmission. ...Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily in HIV-1–infected women during late pregnancy. Methods. We conducted a nonrandomized, open-label, multicenter, phase 4 study. HIV-infected pregnant women receiving rilpivirine 25 mg once daily were included. Intensive 24-hour pharmacokinetic sampling was performed in the third trimester and at least 2 weeks postpartum. Pharmacokinetic parameters were calculated by noncompartmental analysis. Results. Sixteen subjects were included. Geometric mean ratios of third trimester vs postpartum were 0.55 (90% confidence interval CI, .46–.66) for the 24-hour area under the concentration-time curve (AUC0-24h); 0.65 (90% CI, .55–.76) for the maximum concentration; and 0.51 (90% CI, .41–.63) for the minimum observed concentration (Cmin). Four of 16 (25%) subjects had Cmin below the target concentration (0.04 mg/L) in the third trimester of pregnancy. No subtherapeutic levels were observed postpartum. No detectable viral loads were observed in this study. All newborns tested negative for HIV. No birth defects were reported. The median (range, n = 5) rilpivirine cord-to-maternal plasma concentration ratio was 0.50 (range, .35–.81). Conclusions. Rilpivirine exposure is substantially lowered during late pregnancy. Despite lower exposure, virologic suppression was maintained and no perinatal transmission was observed. Overall, these results suggest that rilpivirine 25 mg once daily may be an alternative treatment option for HIV-1–infected pregnant women who are virologically suppressed, in settings where therapeutic drug monitoring and/or close viral load monitoring are feasible to detect suboptimal antiretroviral therapy. Clinical Trials Registration. NCT00825929.
In 1%-5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the ...diagnostic value of
F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up.
All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one
F-FDG PET/CT scan was obtained. Clinical data and results from
F-FDG PET/CT at diagnosis and during follow-up were collected.
F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system.
In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all
F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever-related mortality rate in patients with and without vascular infection based on
F-FDG PET/CT was 23.8% and 2.1%, respectively (
= 0.001). When
F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of
F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of
F-FDG PET/CT scans resulted in treatment modification.
F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival.
The functional activity and differentiation potential of cells is determined by their interaction with surrounding cells. Approaches that allow unbiased characterization of cell states while at the ...same time providing spatial information are of major value to assess this environmental influence. However, most current techniques are hampered by a trade-off between spatial resolution and cell profiling depth. Here, we developed a photocage-based technology that allows isolation and in-depth analysis of live cells from regions of interest in complex
ex vivo
systems, including primary human tissues. The use of a highly sensitive 4-nitrophenyl(benzofuran)-cage coupled to a set of nanobodies allowed high-resolution photo-uncaging of different cell types in areas of interest. Single cell RNA-sequencing of spatially defined CD8
+
T cells was used to exemplify the feasibility of identifying location-dependent cell states. The technology described here provides a valuable tool for analysis of spatially defined cells in diverse biological systems, including clinical samples.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in ...chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18 microg once daily (n=356) compared with ipratropium 40 microg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV1) were 1.25+/-0.43 L (41.9+/-12.7% of the predicted value) (tiotropium) and 1.18+/-0.37 L (39.4+/-10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12+/-0.01 L with tiotropium and declined by 0.03+/-0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.
Objectives
Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil‐fumarate (TDF)‐containing combination antiretroviral therapies (cARTs). This ...statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)‐based cART for HIV‐1‐infected patients.
Methods
An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression < 400 copies/mL, and time to treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score‐adjusted models.
Results
A total of 1582 ART‐naïve HIV‐1‐infected patients initiated 3TC or FTC with TDF and ritonavir‐boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI‐based cART was 0.75 95% confidence interval (CI) 0.32–1.79; P = 0.51. Propensity score‐adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58–2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements < 400 copies/mL within 48 weeks (HR 0.94; 95% CI 0.78–1.16) and the time to treatment failure after suppression < 400 copies/mL (HR 0.94; 95% CI 0.36–2.50) were not significantly influenced by the use of 3TC in TDF/PI‐containing cART.
Conclusions
The virological responses were not significantly different in treatment‐naïve HIV‐1‐infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir‐boosted PI.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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