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Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
The Lancet. Public Health Jul 2024Overdose is the leading cause of death for people released from prison, and opioid agonist treatment is associated with reductions in mortality after imprisonment....
Estimated effects of opioid agonist treatment in prison on all-cause mortality and overdose mortality in people released from prison in Norway: a prospective analysis of data from the Norwegian Prison Release Study (nPRIS).
BACKGROUND
Overdose is the leading cause of death for people released from prison, and opioid agonist treatment is associated with reductions in mortality after imprisonment. However, few studies have explored the interplay of the potential modifiable risk factors and protective factors for mortality after release from prison. We aimed to describe all-cause mortality and overdose mortality among individuals released from Norwegian prisons during 2000-22 and to identify pre-existing risk factors associated with both types of mortality among these individuals for 6 months.
METHODS
For this prospective analysis, we used data from the Norwegian Prison Release Study (nPRIS), which includes all people in prison in Norway between Jan 1, 2000, and Dec 31, 2022; the Norwegian Cause of Death Registry; the Norwegian Prison Registry; the Norwegian Patient Registry; and Statistics Norway. All prisons in Norway that were open during this period were included. People who did not have a Norwegian personal identification number or were serving their sentence outside of prison units were excluded from this analysis. To identify pre-existing risk factors associated with all-cause and overdose mortality among people released from prison, we left-censored the observation period on Jan 1, 2010, creating a subsample of individuals. We calculated crude mortality rates (CMRs) and corresponding 95% CIs as the number of deaths per 100 000 person-years for several time periods after release. The primary outcomes were all-cause mortality and overdose mortality according to the ICD-10, assessed in all participants and analysed via two separate Cox proportional-hazards models.
FINDINGS
The total nPRIS cohort included 112 877 individuals released from prison in Norway between 2000 and 2022, 11 995 (10·6%) of whom were female and 100 865 (89·4%) of whom were male. We identified 13 004 instances of all-cause mortality and 3085 instances of overdose mortality during the 1 463 035 person-years. The estimated CMR for all-cause mortality was 889 (95% CI 874-904) per 100 000 person-years and for overdose mortality was 211 (203-218) per 100 000 person-years. Among people diagnosed with opioid use disorder before entering prison during 2010-22 (n=6830), provision of opioid agonist treatment was estimated to be associated with reductions in both all-cause mortality (hazard ratio 0·58, 95% CI 0·39-0·85) and overdose mortality (0·51, 0·31-0·82) in the 6 months after leaving prison after adjustment for sociodemographic, prison-related, and clinical characteristics.
INTERPRETATION
In people diagnosed with opioid use disorder released from Norwegian prisons, opioid agonist treatment provided while in prison was a protective factor for both all-cause and overdose mortality at 6 months. Provision of opioid agonist treatment while in prison is crucial in reducing mortality for 6 months after release and should be available to all people in prison who have treatment needs.
FUNDING
South-Eastern Norway Regional Health Authority and the Research Council of Norway.
Topics: Humans; Norway; Male; Prospective Studies; Female; Adult; Drug Overdose; Prisoners; Middle Aged; Cause of Death; Prisons; Risk Factors; Analgesics, Opioid; Young Adult; Mortality; Registries; Opiate Substitution Treatment; Adolescent
PubMed: 38942554
DOI: 10.1016/S2468-2667(24)00098-7 -
Annals of Vascular Surgery Jun 2024Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90-days post-operatively after elective endovascular...
OBJECTIVES
Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90-days post-operatively after elective endovascular thoracic and thoracoabdominal aortic repair overall and by extent of coverage.
METHODS
A cohort of index elective non-traumatic endovascular thoracic and thoracoabdominal aortic cases from 2010-2018 was derived from the Vascular Implant Surveillance and Interventional Outcomes Network. Cohort readmissions within 90-days postoperative were examined both overall and by Crawford extent (CE) of aortic coverage. Postoperative mortality was examined by reason for readmission and CE.
RESULTS
The cohort consisted of 2,093 patients who underwent endovascular thoracic and thoracoabdominal aortic repair (1,541 CE 0A/0B; 240 CE 1-3; 312 CE 4-5). Cumulative risk for 90-day readmission was 34.3% in CE 0A/0B repairs, 33.4% in CE4-5 repairs and 47.4% in CE 1-3 repairs. Compared to CE 0A/B, patients with CE 1-3 repairs experienced an increased risk of readmission within 90 days postoperatively after adjusting for preoperative factors (aHR 1.27(1.00,1.61) while the readmission risk for CE 4-5 repairs did not differ significantly (aHR 0.83 (0.64,1.06). Significant risk factors for 90-day readmission included COPD, dialysis dependence, limited ambulation, visceral/spinal ischemia, and in-hospital stroke. Discharge to home was protective against readmission (HR 0.65, CI 0.54-0.79). Patients with a readmission within 90-days had a 7.89-fold increase in 90-day mortality (HR 7.84; 5.17, 11.9) compared to those not readmitted.
CONCLUSIONS
Increasing extent of endovascular thoracic and thoracoabdominal aortic repair was associated with higher 90-day readmission rates. Readmission for all CE was associated with near 8-fold increased risk of mortality. Risk factors associated with increased risk for readmission included pulmonary insufficiency, renal disease, and poor functional status. These findings can inform stakeholders about investment of resources to improve processes of care that both target prevention and mitigate risk of readmission after elective endovascular thoracic and thoracoabdominal aortic repair.
PubMed: 38942375
DOI: 10.1016/j.avsg.2024.05.007 -
Ageing Research Reviews Jun 2024Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized... (Review)
Review
Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized these findings. Five databases were searched from January 1, 2000, to December 30, 2023. The protocol was registered with PROSPERO. Data were extracted and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant meta-analyses of modifiable risk factors were performed. The evidence of each factor was assessed by the GRADE for cohort studies. Of 16,651 citations, 87 studies involving 225,584 community-dwelling seniors were included. Fourteen meta-analyses involving 20 studies with 44,199 participants were performed. The analyses revealed low-to-moderate-quality evidence supporting that diabetes, 2 or more comorbidities, anxiety, apathy, depressive symptoms, and physical frailty were risk factors for incident MCI in older adults. Conversely, hypertension, agitation, and irritability might not be risk factors. Additionally, moderate-quality evidence supports the protective effect of engaging in cognitive-demanding activities on the onset of MCI. Collectively, this study constitutes the first extensive compilation of evidence regarding the various risk factors for the development of MCI in older adults. Our findings hold significant potential to guide the formulation of prevention and management strategies to either prevent or potentially reverse the onset of MCI.
PubMed: 38942197
DOI: 10.1016/j.arr.2024.102350 -
Veterinary Microbiology Jun 2024Postweaning diarrhea (PWD) is a multifactorial disease caused by different aetiological agents, like viruses or bacteria and where the role of the microbiota remains...
Postweaning diarrhea (PWD) is a multifactorial disease caused by different aetiological agents, like viruses or bacteria and where the role of the microbiota remains unclear. The aim of this study was to assess differences between healthy and diarrheic weaned pigs concerning the prevalence of pathogens and changes in the intestinal microbiota. Eighteen farms with PWD were selected and 277 fecal samples were collected (152 diarrheic vs 125 healthy). Presence of Rotavirus A (RVA), B (RVB), C (RVC) and Porcine Epidemic Diarrhea Virus (PEDV), virulence factors of Escherichia coli and Clostridioides difficile were analyzed by PCR. Finally, the microbiota composition was also study by 16 S rRNA sequencing on 148 samples (102 diarrheic vs 46 healthy). RVA (53.95 % vs 36 %, p=0.04) and RVB (49.67 % vs 28.8 %, p<0.001) were more frequent in diarrheic animals. Furthermore, RVA viral load was higher in diseased animals. VT2 toxin was significantly associated with diarrhea, whereas other virulence factors were not. Presence of C. difficile and PEDV was almost negligible. Regarding microbiota changes, Fusobacteriota phylum was more frequent in diarrheic samples and Ruminococcaceae family in healthy penmates. During the first week postweaning, Enterobacteriace and Campylobacteria were enriched in animals presenting diarrhea. Furthermore, Lactobacillus was detected in those individuals with no RVA infection. In conclusion, RVA seems to play a primary role in PWD. Classic E. coli virulence factors were not associated with diarrhea, indicating the need for revising their implication in disease. Moreover, Lactobacillus was found frequently in animals negative for RVA, suggesting some protective effect.
PubMed: 38941767
DOI: 10.1016/j.vetmic.2024.110162 -
Boletin Medico Del Hospital Infantil de... 2024HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent...
BACKGROUND
HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent hosts; however, there are insufficient studies on the duration of seroprotection in HIV-infected children.
METHODS
An analytical cohort study was conducted. HIV-1-infected children who received the inactivated HAV vaccine (2 doses) were included. Blood samples were taken for antibody measurement, the first one 28 days after the second dose and another 7 years after the vaccination schedule. Information on viral load, immunological category, weight, height, and response to antiretroviral treatment from diagnosis to the last assessment was obtained.
RESULTS
19 patients were included, with a mean age of 12.6 years (SD ± 2.29). 58% were male. 80% of the patients presented protective immunoglobulin G antibodies against HAV 7-year post-vaccination. The antibody concentration was found to be between 13 and 80 mIU/mL (median of 80 mIU/mL). 52% showed some degree of immunosuppression. There was no statistically significant relationship between the presence of seroprotection and viral load, treatment failure, immunological category, and malnutrition. Twelve patients presented with antiretroviral treatment failure, and in 33% of them, the antibodies did not offer satisfactory seroprotection.
CONCLUSION
7-year post-vaccination, 80% of HIV-infected children maintain seroprotection titers against HAV.
Topics: Humans; Male; HIV Infections; Child; Hepatitis A Vaccines; Female; Hepatitis A Antibodies; Adolescent; Hepatitis A; Cohort Studies; Viral Load; Time Factors; Follow-Up Studies; Immunoglobulin G; Vaccines, Inactivated
PubMed: 38941633
DOI: 10.24875/BMHIM.23000125 -
JMIR Public Health and Surveillance Jun 2024Suicide is a significant public health issue. Many risk prediction tools have been developed to estimate an individual's risk of suicide. Risk prediction models can go...
BACKGROUND
Suicide is a significant public health issue. Many risk prediction tools have been developed to estimate an individual's risk of suicide. Risk prediction models can go beyond individual risk assessment; one important application of risk prediction models is population health planning. Suicide is a result of the interaction among the risk and protective factors at the individual, health care system, and community levels. Thus, policy and decision makers can play an important role in suicide prevention. However, few prediction models for the population risk of suicide have been developed.
OBJECTIVE
This study aims to develop and validate prediction models for the population risk of suicide using health administrative data, considering individual-, health system-, and community-level predictors.
METHODS
We used a case-control study design to develop sex-specific risk prediction models for suicide, using the health administrative data in Quebec, Canada. The training data included all suicide cases (n=8899) that occurred from January 1, 2002, to December 31, 2010. The control group was a 1% random sample of living individuals in each year between January 1, 2002, and December 31, 2010 (n=645,590). Logistic regression was used to develop the prediction models based on individual-, health care system-, and community-level predictors. The developed model was converted into synthetic estimation models, which concerted the individual-level predictors into community-level predictors. The synthetic estimation models were directly applied to the validation data from January 1, 2011, to December 31, 2019. We assessed the performance of the synthetic estimation models with four indicators: the agreement between predicted and observed proportions of suicide, mean average error, root mean square error, and the proportion of correctly identified high-risk regions.
RESULTS
The sex-specific models based on individual data had good discrimination (male model: C=0.79; female model: C=0.85) and calibration (Brier score for male model 0.01; Brier score for female model 0.005). With the regression-based synthetic models applied in the validation data, the absolute differences between the synthetic risk estimates and observed suicide risk ranged from 0% to 0.001%. The root mean square errors were under 0.2. The synthetic estimation model for males correctly predicted 4 of 5 high-risk regions in 8 years, and the model for females correctly predicted 4 of 5 high-risk regions in 5 years.
CONCLUSIONS
Using linked health administrative databases, this study demonstrated the feasibility and the validity of developing prediction models for the population risk of suicide, incorporating individual-, health system-, and community-level variables. Synthetic estimation models built on routinely collected health administrative data can accurately predict the population risk of suicide. This effort can be enhanced by timely access to other critical information at the population level.
Topics: Humans; Quebec; Male; Suicide; Female; Case-Control Studies; Adult; Risk Assessment; Middle Aged; Aged; Adolescent; Young Adult; Risk Factors
PubMed: 38941610
DOI: 10.2196/52773 -
Blood Advances Jun 2024Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in...
Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in preeclampsia remains controversial. LMWH may convey beneficial effects in preeclampsia independent of their anti-coagulant activity, possibly by inhibiting inflammation. Here we evaluated whether LMWH inhibit placental thrombo-inflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle (EV)-induced and platelet-dependent preeclampsia-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation and improves trophoblast proliferation in-vivo and in-vitro. Moreover, LMWH inhibits platelet independent trophoblast NLRP3 inflammasome activation. Mechanistically, LWMH activates via Heparin binding epidermal growth factor (HBEGF) signaling the PI3-Kinase-AKT pathway in trophoblasts thus preventing inflammasome activation. In human preeclampsia placental explants, inflammasome activation and PI3-Kinase-AKT signaling events were reduced with LMWH treatment compared to those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates preeclampsia-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in preeclampsia and identify a signaling mechanism through which LMWH ameliorates preeclampsia, thus providing a rationale for the use of LMWH in preeclampsia.
PubMed: 38941535
DOI: 10.1182/bloodadvances.2023011895 -
Medicine Jun 2024Previous studies have reported an association between physical activity and the occurrence and progression of knee osteoarthritis (KOA). However, the existing evidence...
Previous studies have reported an association between physical activity and the occurrence and progression of knee osteoarthritis (KOA). However, the existing evidence remains limited and of low-quality. This study aimed to examine the causal relationship between different levels of physical activity and KOA. Instrumental variables, represented by single nucleotide polymorphisms (SNPs), were utilized to capture sedentary behavior, appropriate physical exercise, and excessive physical activity. Aggregated statistics from the UK Biobank genome-wide association study dataset were used to assess the impact of these SNPs on KOA. Causality was estimated using inverse variance weighting (IVW), MR Egger, simple model, weighted median, and weighted model approaches. The stability of the results was assessed through heterogeneity and sensitivity analyses. Mendelian randomization (MR) analysis revealed a strong association between sedentary behavior and KOA, with an odds ratio (OR) of 2.096 (95% CI: 1.506-2.917) and a P value of 1.14 × 10-5. Appropriate physical exercise behavior exhibited a strong negative association with KOA, with an OR of 0.147 (95% CI: 0.037-0.582) and a P value of 0.006. Conversely, excessive physical activity behavior showed a significant positive association with KOA, with an OR of 2.162 (95% CI: 1.327-3.521) and a P value of .002. Our findings indicate that sedentary behavior and excessive physical activity are identified as risk factors for KOA, whereas engaging in appropriate physical exercise emerges as a protective factor against the development of KOA.
Topics: Humans; Osteoarthritis, Knee; Mendelian Randomization Analysis; Exercise; Polymorphism, Single Nucleotide; Sedentary Behavior; Genome-Wide Association Study; Male; Female; Risk Factors; United Kingdom; Middle Aged
PubMed: 38941438
DOI: 10.1097/MD.0000000000038650 -
Revista de La Facultad de Ciencias... Jun 2024Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD).
INTRODUCTION
Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD).
AIM
The aim of this study was to determine food intakes patters and estimate risk of GD.
METHODS
A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks.
RESULTS
The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish).
CONCLUSION
Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.
Topics: Humans; Argentina; Female; Male; Case-Control Studies; Cross-Sectional Studies; Middle Aged; Adult; Risk Factors; Feeding Behavior; Retrospective Studies; Cholelithiasis; Aged; Diet; Prevalence
PubMed: 38941231
DOI: 10.31053/1853.0605.v81.n2.36961