Many HIV-affected couples living in sub-Saharan Africa desire to have children, but few quantitative studies have examined support for their childbearing needs. Our study explored client-provider ...communication about childbearing and safer conception among HIV clients in Uganda.
400 Ugandan HIV clients in committed relationships and with intentions to conceive were surveyed. Knowledge, attitudes and practices related to childbearing, and use of safer conception methods were assessed, including communication with providers about childbearing needs, the correlates of which were examined with bivariate statistics and logistic multivariate analysis.
75% of the sample was female; 61% were on antiretroviral therapy; and 61% had HIV-negative or unknown status partners. Nearly all (98%) reported the desire to discuss childbearing intentions with their HIV provider; however, only 44% reported such discussions, the minority (28%) of which was initiated by the provider. Issues discussed with HIV providers included: HIV transmission risk to partner (30%), HIV transmission risk to child (30%), and how to prevent transmission to the child (27%); only 8% discussed safer conception methods. Regression analysis showed that those who had communicated with providers about childbearing were more likely to have been diagnosed with HIV for a longer period OR (95% CI) = 1.09 (1.03, 1.15), while greater internalized childbearing stigma was associated with lower odds of this communication OR (95% CI) = 0.70 (0.49, 0.99), after controlling for all bivariate correlates and basic demographics.
Communication between HIV clients and providers about childbearing needs is poor and associated with stigma. Innovations to mitigate stigma among clients as well as training to improve health worker communication and skills related to safer conception counseling is needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2) -targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with ...HER2-positive metastatic breast cancer (MBC).
Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR).
Sixty-four patients (43 patients in the second-line or greater setting advanced MBC; 21 patients in the first-line setting first-line MBC) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade ≥ 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively).
T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.
For birds in urban environments, the configuration of local habitat within the landscape may be as critical as the composition of the local habitat itself. We examined the relative importance of ...environmental attributes (e.g., tree cover, composition, and number of tree species) measured at different spatial scales in relation to urban bird species richness and abundance. We expected that some bird species and nesting guilds would have a closer association with landscape-level features (within 1000 m), such as proximity to large forested areas, than with local-scale habitat measures (within 50 m). To investigate this, avian community data were collected at 285 point-count stations in 1997 and 1998 along four roadside transects located in Vancouver and Burnaby, British Columbia, Canada. Transects (5–25 km in length) bisected three large parks (>324 ha) and proceeded along residential streets in urban and suburban areas. In total, 48 bird species were observed, including 25 common species. Species richness declined in relation to a gradient of increasing urbanization, as measured by local- and landscape-level habitat features. We further examined the significance and importance of local- vs. landscape-level habitat attributes using logistic regression and found that both scales explained the presence/absence distributions of residential birds. Local-scale habitat features such as large coniferous trees, berry-producing shrubs, and freshwater streams were of particular importance in estimating the likelihood of finding bird species. Landscape measures, particularly forest cover (within 500 m) and park area (measured at different scales as a function of distance from point-count stations) significantly improved likelihood estimations based solely on local-scale habitat features. Our results suggest that both local- and landscape-scale resources were important in determining the distribution of birds in urban areas. Parks, reserves, and the surrounding residential areas should be integrated into urban planning and development designs to maintain resident avifauna and overall species diversity in urban environments.
IMPORTANCE: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The ...comparative effect of these drugs on mortality is unknown. OBJECTIVE: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. DESIGN, SETTING, AND PARTICIPANTS: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. INTERVENTIONS: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. RESULTS: Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean SD age, 58 17.0 years; 9691 36.1% were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 95% CI, 1.00 to 1.10; absolute risk difference, 0.93 percentage points 95% CI, −0.01 to 1.88 percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 95% CI, 0.57 to 0.92; absolute risk difference, −0.51 percentage points 95% CI, −0.90 to −0.12 percentage points; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. CONCLUSIONS AND RELEVANCE: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12616000481471
Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, ...pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Depression consistently predicts nonadherence to human immunodeficiency virus antiretroviral therapy, but which aspects of depression are most influential are unknown. Such knowledge could ...inform assessments of adherence readiness and the type of depression treatment to utilize.
Purpose
We examined how depression severity, symptom type, and change over time relate to adherence.
Methods
Microelectronic adherence and self-reported depression data from 1,374 participants across merged studies were examined with cross-sectional and longitudinal analyses. Depression variables included a continuous measure, categorical measure of severity, cognitive and vegetative subscales, and individual symptoms.
Results
At baseline, mean adherence was 69%, and 25% had mild/moderate and 18% had severe depression. In cross-sectional multivariate analyses, continuous depression, cognitive depressive symptoms, and severe depression were associated with lower adherence. In longitudinal analysis, reductions in both continuous and categorical depression predicted increased adherence.
Conclusions
The relationship between global continuous depression and nonadherence was statistically significant, but relatively weak compared to that of cognitive depressive symptoms and severe depression, which appear to pose strong challenges to adherence and call for the need for early detection and treatment of depression.
In a randomized trial involving men with hypogonadism and preexisting or a risk of cardiovascular disease, testosterone therapy was noninferior to placebo with respect to major adverse cardiac events.
This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to ...consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.
•IUR built better scientific consensus on the ecological effects of radiation.•Laboratory versus field approaches have been addressed.•Organism versus population and ecosystemic inference strategies have been addressed.•Dose estimation approaches and their significance under chronic exposure conditions.•Seven consensus statements about environmental protection against radiation are given.
Among people living with HIV in Uganda, desires to have a child and unplanned pregnancies are both common, while utilization of safer conception methods (SCM) and modern contraceptives are low.
Three ...hundred eighty-nine HIV clients who reported considering childbearing with their uninfected partner enrolled in a safer conception counseling intervention trial in Uganda. Multiple regression analysis and baseline data were used to examine correlates of reproductive intentions and behaviors, including use of safer conception methods and contraception.
Most (n = 313; 80.5%) reported that both they and their partner wanted to have a child now, which was associated with being married, in a longer relationship, not having a child with partner, greater SCM knowledge, lower internalized childbearing stigma, and higher perceived community stigma of childbearing. However, just 117 reported trying to conceive in the prior 6 months, which was associated with being female, not having a child with their partner, less decision-making control within the relationship, and greater perceived cultural acceptability of SCM. Among those who had tried to conceive in the past 6 months, 14 (11.9%) used SCM, which was associated with greater control in decision making. Of the 268 who were not trying to conceive, 69 (25.7%) were using a modern contraceptive, which was associated with being in a shorter relationship, less control over decision-making, more positive attitudes towards contraception and lower depression.
Methods to promote reproductive goals are underused by HIV serodiscordant couples, and relationships characteristics and childbearing-related stigma appear to be most influential and thus targets for intervention.
Clinicaltrials.gov, NCT03167879 ; date registered May 23, 2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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