Risk factors for and preventability of drug-related hospital revisits in older patients: A post-hoc analysis of a randomized clinical trial.

AIM: The aims of this study were (1) to identify older patients' risk factors for drug-related readmissions and (2) to assess the preventability of older patients' drug-related revisits. METHODS: Post hoc analysis of a randomized clinical trial with patients aged ≥65 years at eight wards within four hospitals in Sweden. (1) The primary outcome was risk factors for drug-related readmission within 12 months post-discharge. A Cox proportional hazards model was made with sociodemographic and clinical baseline characteristics. (2) Four hundred trial participants were randomly selected and their revisits (admissions and emergency department visits) were assessed to identify potentially preventable drug-related revisits, related diseases and causes. RESULTS: (1) Among 2637 patients (median age 81 years), 582 (22%) experienced a drug-related readmission within 12 months. Sixteen risk factors (hazard ratio >1, P < 0.05) related to age, previous hospital visits, medication use, multimorbidity and cardiovascular, liver, lung and peptic ulcer disease were identified. (2) The 400 patients experienced a total of 522 hospital revisits, of which 85 (16%) were potentially preventable drug-related revisits. The two most prevalent related diseases were heart failure (n = 24, 28%) and chronic obstructive pulmonary disease (n = 13, 15%). The two most prevalent causes were inadequate treatment (n = 23, 27%) and insufficient or no follow-up (n = 22, 26%). CONCLUSION: (1) Risk factors for drug-related readmissions in older hospitalized patients were age, previous hospital visits, medication use and multiple diseases. (2) Potentially preventable drug-related hospital revisits are common and might be prevented through adequate pharmacotherapy and continuity of care in older patients with cardiovascular or lung disease.

Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data.

BACKGROUND: In cardiovascular disease, prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, hypercholesterolaemia, and smoking) are crucial; however, myocardial infarction in the absence of SMuRFs is not infrequent. The outcomes of individuals without SMuRFs are not well known. METHODS: We retrospectively analysed adult patients with first-presentation ST-elevation myocardial infarction (STEMI) using data from the Swedish myocardial infarction registry SWEDEHEART. Clinical characteristics and outcomes of adult patients (age ≥18 years) with and without SMuRFs were examined overall and by sex. Patients with a known history of coronary artery disease were excluded. The primary outcome was all-cause mortality at 30 days after STEMI presentation. Secondary outcomes included cardiovascular mortality, heart failure, and myocardial infarction at30 days. Endpoints were also examined up to discharge, and to the end of a 12-year follow-up. Multivariable logistic regression models were used to compare in-hospital mortality, and Cox-proportional hazard models and Kaplan-Meier analysis for long-term outcomes. FINDINGS: Between Jan 1, 2005, and May 25, 2018, 9228 (14·9%) of 62 048 patients with STEMI had no SMuRFs reaching diagnostic thresholds. Median age was similar between patients with SMuRFs and patients without SMuRFs (68 years [IQR 59-78]) vs 69 years [60-78], p<0·0001). SMuRF-less patients had a similar rate of percutaneous coronary intervention to those with at least one modifiable risk factor, but were significantly less likely to receive statins, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockade (ARB), or ß-blockers at discharge. By 30 days after presentation, all-cause mortality was significantly higher in SMuRF-less patients (hazard ratio 1·47 [95% CI 1·37-1·57], p<0·0001). SMuRF-less women had the highest 30-day mortality (381 [17·6%] of 2164), followed by women with SMuRFs (2032 [11·1%] of 18 220), SMuRF-less men (660 [9·3%] of 7064), and men with SMuRFs (2117 [6·1%] of 34 600). The increased risk of 30-day all-cause mortality in SMuRF-less patients remained significant after adjusting for age, sex, left ventricular ejection fraction, creatinine, and blood pressure, but was attenuated on inclusion of pharmacotherapy prescription (ACEI or ARB, ß-blocker, or statin) at discharge. Additionally, SMuRF-less patients had a significantly higher rate of in-hospital all-cause mortality than patients with one or more SMuRF (883 [9·6%] vs 3411 [6·5%], p<0·0001). Myocardial infarction and heart failure at 30 days were lower in SMuRF-less patients. All-cause mortality remained increased in the SMuRF-less group for more than 8 years in men and up to the 12-year endpoint in women. INTERPRETATION: Individuals who present with STEMI in the absence of SMuRFs have a significantly increased risk of all-cause mortality, compared with those with at least one SMuRF, which was particularly evident in women. The increased early mortality rates are attenuated after adjustment for use of guideline-indicated treatments, highlighting the need for evidence-based pharmacotherapy during the immediate post-infarct period irrespective of perceived low risk. FUNDING: Swedish Heart and Lung Foundation, National Health and Medical Research Council (Australia).

Live birth, cumulative live birth and perinatal outcome following assisted reproductive treatments using donor sperm in single women vs. women in lesbian couples: a prospective controlled cohort study.

PURPOSE: Assisted reproductive technology (ART) treatments with donor sperm have been allowed for women in lesbian relationships (WLR) since 2005 in Sweden, but for single women (SW), these became approved only recently in 2016. This study was conducted to compare the outcomes of ART treatments in SW vs. WLR. METHODS: This is a prospective controlled cohort study of 251 women undergoing intrauterine insemination (D-IUI) or in vitro fertilization (D-IVF) using donor sperm between 2017 and 2019 at the department of Reproductive Medicine, Karolinska University Hospital. The cohort comprised 139 SW and 112 WLR. The main outcomes included differences in live birth rate (LBR) and cumulative live birth rate (cLBR) between the groups. The SW underwent 66 D-IUI and 193 D-IVF treatments and WLR underwent 255 D-IUI and 69 D-IVF treatments. Data on clinical characteristics, treatment protocols and clinical outcomes were extracted from the clinic's electronic database. The outcomes of D-IUI and D-IVF were separately assessed. RESULTS: The cohort of SW was significantly older than WLR (37.6 vs. 32.4 years, P < 0.001), and more commonly underwent IVF at first treatment (83% vs. 29%, P < 0.000). Conversely, WLR underwent more frequently D-IUI as a first treatment (71% vs. 17% of SW, P < 0.001) and more often in the natural cycle (89.9% vs. 70.8%, P = 0.019), respectively. There was no statistically significant difference in the main outcome LBR between the two groups, or between the two different types of treatment, when adjusted for age. Perinatal outcomes and cLBR were also similar among the groups. CONCLUSIONS: SW were, on average, older than WLR undergoing treatment with donor sperm. No significant differences were seen in the LBR and cLBR when adjusted for age between the two groups and between the two types of treatment (D-IVF vs. D-IUI). TRIAL REGISTRATION: ClinicalTrials.gov NTC04602962.

Risk markers of incident atrial fibrillation in patients with coronary heart disease.

BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.

The facial nerve palsy and cortisone evaluation (FACE) study in children: protocol for a randomized, placebo-controlled, multicenter trial, in a Borrelia burgdorferi endemic area.

BACKGROUND: Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults. METHOD: This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1-17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy. DISCUSSION: This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas. TRIAL REGISTRATION: The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017-004187-35) and published at ClinicalTrials.gov ( NCT03781700 , initial release 12/14/2018).

Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF.

RESEARCH QUESTION: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? DESIGN: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. RESULTS: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. CONCLUSION: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.

Endometriosis and cumulative live birth rate after fresh and frozen IVF cycles with single embryo transfer in young women: no impact beyond reduced ovarian sensitivity-a case control study.

PURPOSE: To investigate the impact of symptomatic and surgically confirmed endometriosis on ovarian sensitivity index (OSI) and cumulative live-birth rates (LBR) using predominantly single embryo transfer (SET). METHODS: Cross-sectional case-control study in a University-based ART program. Women with symptomatic and surgically confirmed endometriosis (N = 172), who underwent IVF/ICSI at Karolinska University Hospital were compared to controls without clinically suspected endometriosis (N = 2585). Two thousand seven hundred fifty-seven patients underwent 8236 treatment cycles (4598 fresh and 3638 frozen cycles). Primary outcome measures included Ovarian Sensitivity Index (OSI) estimated as collected oocytes/FSH dose and cumulative LBR/oocyte pickup (OPU). Generalized estimated equation (GEE) model accounting for dependencies between consecutive treatments were applied. Secondary outcomes included number of oocytes, pregnancy rate per OPU and per ET, LBR per ET, and miscarriage rate. RESULTS: Patients diagnosed with endometriosis had significantly fewer oocytes collected (8.47 vs. 9.54, p = 0.015) and lower OSI (p = 0.011) than controls. There were no differences in cycle cancelations (p = 0.59) or miscarriages (p = 0.95) between the two groups. Cumulative LBR/OPU did not differ between women with endometriosis and controls (35.6% vs. 34.7%, respectively, p = 0.83). In both groups, more than 60% of women had consecutive FETs after fresh ETs (p = 0.49) with SET in > 70% of cases. The results were similar whether ovarian endometrioma was present or not. CONCLUSIONS: Our data support that a diagnosis of endometriosis, with or without present endometrioma, does not negatively affect ART cumulative results. The impact of endometriosis was discernible on OSI but not on clinical relevant outcomes including pregnancy and LBR.

Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, ß-blockers, dual antiplatelet therapy, and long-term cardiovascular events. METHODS: This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199 162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. RESULTS: At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68-0.87), 0.82 (0.73-0.93), and 0.86 (0.74-1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and ß-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74-1.08). CONCLUSIONS: The results indicate long-term beneficial effects of treatment with statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on outcome in patients with MINOCA, a trend toward a positive effect of ß-blocker treatment, and a neutral effect of dual antiplatelet therapy. Properly powered randomized clinical trials to confirm these results are warranted.

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

STUDY QUESTION: Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? SUMMARY ANSWER: A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. WHAT IS KNOWN ALREADY: Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. STUDY DESIGN, SIZE, DURATION: This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.

Does ovarian stimulation regimen affect IVF outcome? a two-centre, real-world retrospective study using predominantly cleavage-stage, single embryo transfer.

In this study, ovarian stimulation using highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) for IVF were compared in two large assisted reproduction technique centres in Sweden. A total of 5902 women underwent 9631 oocyte retrievals leading to 8818 embryo transfers (7720 on day 2): single embryo transfers (74.2%); birth rate per embryo transfer (27.7%); multiple birth rate (5.0%); incidence of severe ovarian hyperstimulation syndrome (0.71%). Compared with ovarian stimulation with rFSH, women who received HP-HMG were older, had higher dosages of gonadotrophins administered, fewer oocytes retrieved and more embryos transferred. After multivariate analysis controlling for age and generalized estimating equation model, no differences were found in delivery outcomes per embryo transfers between HP-HMG and rFSH, independent of gonadotrophin releasing hormone analogue (GnRH) used. Logit curves for live birth rate suggested differences for various subgroups, most prominently for women with high oocyte yield or when high total doses were used. Differences were not significant, perhaps owing to skewed distributions of the FSH compounds versus age and other covariates. These 'real-life patients' had no differences in live birth rate between HP-HMG and rFSH overall or in subgroups of age, embryo score, ovarian sensitivity or use of GnRH analogue regimen.

Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery.

BACKGROUND: A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient. METHODS: In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years. RESULTS: UMIs were found in 25% of patients. There was a strong association between stenotic lesions (≥70% stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis ≥ 70% as compared to < 70% (OR 5.1, CI 3.1-8.3, p < 0.0001). 56% of the UMIs were located in the inferior and infero-lateral myocardial segments, despite predominance for stenotic lesions in the left anterior descending artery. CONCLUSION: UMI is common in patients with stable angina and the results indicate that the majority of the UMIs are of ischemic origin due to severe coronary atherosclerosis. In contrast to what is seen in recognized myocardial infarctions, UMIs are predominately located in the inferior and infero-lateral myocardial segments. TRIAL REGISTRATION: The PUMI study is registered at ClinicalTrials.gov (NCT01257282).

Comparing four ovarian reserve markers--associations with ovarian response and live births after assisted reproduction.

INTRODUCTION: We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation. MATERIAL AND METHODS: This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Müllerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c-statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyper-stimulation (defined by the ovarian sensitivity index). RESULTS: All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH (r = 0.71, p < 0.0001). Univariately, AMH and age equivalently predicted live birth (c-statistic 0.61), and together they provided a significantly better model (c-statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age (c-statistic 0.89). CONCLUSIONS: AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.

In Vitro Fertilization/Intracytoplasmic Sperm Injection with Autologous Oocytes in Healthy Women of Advanced Maternal Age: A Comparative Study Investigating Obstetric and Perinatal Outcomes Through Single Versus Double Embryo Transfer.

Introduction: The aim of this study was to assess whether the choice between double embryo transfer (DET) and single embryo transfer (SET) in healthy women of advanced maternal age (AMA) was associated with an increased risk of adverse outcomes. Materials and Methods: Healthy women aged 39-40 years who achieved live birth after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment between 2009 and 2020 at Karolinska University Hospital, Stockholm in Sweden, were included in this prospective, single-center cohort study. Results: A total of 310 women, who underwent IVF/ICSI treatments and achieved live births, were included in our analysis. Within this cohort, 78% of the women received SET, while 22% received DET. Nulliparity was common in both the SET (62.7%) and DET (85.3%) groups. Fresh embryo transfers were more prevalent in the DET group (91.2%) than in the SET group (31.1%). The rate of pregnancy-induced hypertension was higher in the SET group (8.3%) compared to the DET group (1.5%, p = 0.048). Furthermore, the DET group had a significantly higher rate of twin pregnancies (13.2%) compared to the SET group (0.4%). No statistically significant differences were observed in composite obstetric and perinatal complications between the SET and DET groups across all model estimates following different adjustments.Clinical Trial Registration number: ClinicalTrials.gov NTC04602962. Conclusions: While DET was more common in nulliparous women and associated with a higher rate of twin pregnancies, our analysis did not reveal significant differences in adverse outcomes between the SET and DET groups after comprehensive adjustments. Our study suggests that in the absence of co-morbidities, meticulous patient selection coupled with comprehensive maternal care can potentially mitigate potential DET-associated risks in women of AMA.

Associations between psychosocial burden and prognostic biomarkers in patients with chronic coronary syndrome: a STABILITY substudy.

AIM: To investigate associations between psychosocial burden and biomarkers reflecting pathophysiological pathways in patients with chronic coronary syndrome. METHODS: Psychosocial (PS) factors were collected from self-assessed questionnaires and biomarkers representing inflammation (high-sensitivity [hs]-C-reactive protein [CRP], interleukin-6 [IL-6], lipoprotein-associated phospholipase A2 [Lp-PLA2]) and cardiac injury/stress (hs-troponin T [hs-TnT], N-terminal pro-B type natriuretic peptide [NT-proBNP]) were measured in 12,492 patients with chronic coronary syndrome in the STABILITY trial. Associations between level of each psychosocial factor (never-rarely (reference), sometimes, often-always) and biomarkers were evaluated using linear models with adjusted geometric mean ratios (GMR). A score comprising four factors ('feeling down', 'loss of interest', financial stress', 'living alone') that previously demonstrated association with cardiovascular (CV) outcome was created, and categorized into three levels: low, moderate and high PS burden. Associations between PS score and biomarkers were evaluated similarly. RESULTS: Greater PS burden was significantly associated with a gradual increase in inflammatory biomarkers (GMR [95% CI] for moderate vs low PS burden; and high vs low PS burden): hs-CRP (1.09 [1.04-1.14]; 1.12 [1.06-1.17]), IL-6 (1.05 [1.02-1.07]; 1.08 [1.05-1.11]), LpPLA2 (1.01 [1.00 - 1.02]; 1.02 [1.01-1.04]) and cardiac biomarkers hs-TnT (1.03 [1.01-1.06]; 1.06 [1.03-1.09]) and NT-proBNP (1.09 [1.04-1.13]; 1.21 [1.15-1.27]). CONCLUSIONS: In patients with chronic coronary syndrome, greater psychosocial burden was associated with increased levels of inflammatory and cardiac biomarkers. While this observational study does not establish causal nature of these associations, the findings suggest inflammation and cardiac injury/stress as plausible pathways linking psychosocial burden to an elevated CV risk, that needs to be further explored.

We studied the association between psychosocial factors and various circulating protein biomarkers, reflecting different underlying mechanisms of disease, with the hope of shedding light on the link between psychological factors like depression and stress and the risk of cardiovascular events in patients with chronic coronary syndrome. We analysed data from the global large-scale STABILITY trial, which included more than 12,000 patients with chronic coronary syndrome. Participants filled out a questionnaire assessing their level of psychosocial burden, including experiences of depressive symptoms, stress at home, at work and financial stress. Additionally, blood samples were collected in which biomarkers (NTproBNP, high-sensitive Troponin-T, Interleukin-6, CRP and LpPLA2) were analysed. Our findings revealed a significant association between higher psychosocial burden and increased concentrations of biomarkers in patients with chronic coronary syndrome. These biomarkers reflect both inflammatory processes and cardiac damage or dysfunction which could be potential disease mechanisms explaining the increased risk of adverse events in patients with chronic coronary syndrome and high psychosocial burden. Although causal relationships cannot be determined from this study, the findings suggest that inflammation and cardiac stress may play crucial roles in linking psychosocial factors to heightened cardiovascular risk in this patient population. These insights could pave the way for better understanding and managing cardiovascular health in individuals with chronic coronary syndrome, offering hope for more targeted interventions in the future.

Continuous chest compressions are associated with higher peak inspiratory pressures when compared to 30:2 in an experimental cardiac arrest model.

BACKGROUND: Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model. METHODS: Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy. RESULTS: In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups. CONCLUSIONS: Ventilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.

Temporal trends in cardiovascular risk factors, lifestyle and secondary preventive medication for patients with myocardial infarction attending cardiac rehabilitation in Sweden 2006-2019: a registry-based cohort study.

OBJECTIVES: Registries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). DESIGN: A registry-based cohort study. SETTING: All coronary care units and cardiac rehabilitation (CR) centres in Sweden. PARTICIPANTS: Patients attending a CR visit at 1-year post-MI 2006-2019 were included (n=81 363, 18-74 years, 74.7% men). OUTCOME MEASURES: Outcome measures at 1-year follow-up included blood pressure (BP) <140/90 mm Hg, low-density lipoprotein-cholesterol (LDL-C)<1.8 mmol/L, persistent smoking, overweight/obesity, central obesity, diabetes prevalence, inadequate physical activity, and prescription of secondary preventive medication. Descriptive statistics and testing for trends were applied. RESULTS: The proportion of patients attaining the targets for BP<140/90 mmHg increased from 65.2% (2006) to 86.0% (2019), and LDL-C<1.8 mmol/L from 29.8% (2006) to 66.9% (2019, p<0.0001 both). While smoking at the time of MI decreased (32.0% to 26.5%, p<0.0001), persistent smoking at 1 year was unchanged (42.8% to 43.2%, p=0.672) as was the prevalence of overweight/obesity (71.9% to 72.9%, p=0.559). Central obesity (50.5% to 57.0%), diabetes (18.2% to 27.2%) and patients reporting inadequate levels of physical activity (57.0% to 61.5%) increased (p<0.0001 for all). From 2007, >90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, p<0.0001). CONCLUSIONS: While little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006-2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment.

BACKGROUND: Concerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure. OBJECTIVE: Our aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid. METHODS: April-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman's partial correlations were adjusted for age, parity and BMI. RESULTS: Significant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation ρ = 0.41 (confidence interval 0.21-0.47), p < 0.001); hens' egg consumption was positively associated with PFOS (ρ = 0.30 (0.15-0.43), p = 0.007) and PFUnDA (ρ = 0.27 (0.12-0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (ρ = 0.34 (0.20-0.47), p < 0.001) and PFDA (ρ = 0.27 (0.13-0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid. IMPACT STATEMENT: This study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail.

Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease - A STABILITY Substudy.

BACKGROUND The obesity paradox states that patients with higher body mass index (BMI) and cardiovascular disease may experience better prognosis. However, this is less clear in patients with coronary heart disease. METHODS AND RESULTS The prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial included 15 828 patients with stable coronary heart disease with 3 to 5 years' follow-up on optimal secondary preventive treatment. BMI was measured at baseline (n=15 785). Associations between BMI and cardiovascular outcomes were evaluated by Cox regression analyses with multivariable adjustments. Mean age was 64±9 years and 19% women. Most risk markers (diabetes, hypertension, inflammatory biomarkers, triglycerides) showed a graded association with higher BMI. The frequency of smoking, levels of high-density lipoprotein, growth differentiation factor 15, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were higher at lower BMI. Low BMI (<20 kg/m2; n=244 [1.5%]) was associated with doubled risk of total death (hazard ratio [HR], 2.27; 95% CI, 1.60-3.22), cardiovascular death (HR, 2.26; 95% CI, 1.46-3.49), and heart failure (HR, 2.51; 95% CI, 1.35-4.68) compared with BMI of 25 to <30 kg/m2 (n=6752 [42.8%]) as reference. Similarly, high BMI of ≥35 kg/m2 (n=1768 [11.2%]) was associated with increased risk of the same outcomes. A BMI between 20 and <25 kg/m2 was associated with increased risk of cardiovascular death (HR, 1.26; 95% CI, 1.03-1.54) and total death (HR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS Patients with stable coronary heart disease showed a graded increase in cardiometabolic and inflammatory risk factors with increasing BMI category >25 kg/m2. All-cause and cardiovascular mortality were lowest at BMI of 25 to 35 kg/m2. Underweight with BMI of <20 kg/m2 and very high BMI of ≥35 kg/m2 were strong risk markers for poor prognosis. REGISTRATION URL: https://clinicaltrials.gov/; Unique identifier NCT00799903.

Mortality and Cardiovascular Outcomes in Patients Presenting With Non-ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry.

Background A significant proportion of patients with ST-segment-elevation myocardial infarction (MI) have no standard modifiable cardiovascular risk factors (SMuRFs) and have unexpected worse 30-day outcomes compared with those with SMuRFs. The aim of this article is to examine outcomes of patients with non-ST-segment-elevation MI in the absence of SMuRFs. Methods and Results Presenting features, management, and outcomes of patients with non-ST-segment-elevation MI without SmuRFs (hypertension, diabetes, hypercholesterolemia, smoking) were compared with those with SmuRFs in the Swedish MI registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies; 2005-2018). Cox proportional hazard models were used. Out of 99 718 patients with non-ST-segment-elevation MI, 11 131 (11.2%) had no SMuRFs. Patients without SMuRFs had higher all-cause and cardiovascular mortality at 30 days (hazard ratio [HR], 1.20 [95% CI, 1.10-1.30], P<0.0001; and HR, 1.25 [95% CI, 1.13-1.38]), a difference that remained after adjustment for age and sex. SMuRF-less patients were less likely to receive secondary prevention statins (76% versus 82%); angiotensin-converting enzyme inhibitors/angiotensin receptor blockade (54% versus 72%); or ß-blockers (81% versus 87%, P for all <0.0001), with lowest rates observed in women without SMuRFs. In patients who survived to 30 days, rates of all-cause and cardiovascular death were lower in patients without SMuRFs compared with those with risk factors, over 12 years. Conclusions One in 10 patients presenting with non-ST-segment-elevation MI present without traditional risk factors. The excess 30-day mortality rate in this group emphasizes the need for both improved population-based strategies for prevention of MI, as well as the need for equitable evidence-based treatment at the time of an MI.