Comparison of Patients' Ethical Perspectives of Preimplantation Embryo Genetic Testing for Aneuploidy (PGT-A) vs. Monogenic Disorders (PGT-M).

What are the ethical perspectives of preimplantation genetic testing in patients using/considering PGT-A compared to those using/considering PGT-M? A 17-item questionnaire administered online was used to assess ethical perspectives in US patients who recently used/considered PGT-A (n=80) vs. those who used/considered PGT-M (n=72). Kruskal-Wallis, Chi-square, and Fisher exact tests were conducted with STATA. Most PGT-A and PGT-M users/considerers supported using PGT to screen for diseases fatal in childhood (86-89%) and those causing lifelong disabilities (76-79%) and opposed using PGT to screen for non-medical physical (80-87%) or intellectual traits (74-86%). Both groups agreed that PGT aids in parental decision-making, although some expressed concern over its potential to lead to unforeseen consequences for society and the PGT offspring. More PGT-M than PGT-A users/considerers opposed implanting genetically abnormal embryos when requested by parents (29% PGT-A vs. 56% PGT-M, p = 0.007). For embryo disposition, more PGT-A users/considerers favored freezing (95% PGTA vs. 82% PGT-M, p = 0.018) or donating genetically normal embryos to research (73% PGT-A vs. 57% PGT-M, p = 0.044), while more PGT-M users/considerers supported donating embryos with known genetic abnormalities to research (56% PGT-A vs. 81% PGT-M, p = 0.001). Regardless of the reason for using PGT, users generally agreed on the acceptable and unacceptable uses for it, as well as the potential societal impact. PGT-M users/considerers expressed more opposition than PGT-A users/considerers to implanting embryos with a genetic alteration when requested by the parents.

Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates.

OBJECTIVE: Perimenopause is associated with declines in attention, working memory and verbal memory; however, there are significant individual differences. Further, the contributions of hormones and menopausal symptoms to domain-specific cognitive functions remain unknown. This longitudinal study aimed to determine whether there were distinct cognitive profiles in perimenopause and to identify factors associated with each profile. DESIGN: In a sample of 85 women evaluated over 400 bi-annual visits, we administered a comprehensive neuropsychological battery, assessed menopausal symptoms and measured 17ß-estradiol and follicle stimulating hormone. Multilevel latent profile analysis was used to identify cognitive profiles. Regressions were conducted to determine differences in hormones and symptoms by profile after adjusting for Stages of Reproductive Aging Workshop + 10 (STRAW + 10) stage and demographic factors. RESULTS: Perimenopausal cognitive profiles consisted of cognitively normal (Profile 1; n = 162), weaknesses in verbal learning and memory (Profile 2; n = 94), strengths in verbal learning and memory (Profile 3; n = 98) and strengths in attention and executive function (Profile 4; n = 61). Profile 2 was differentiated by less hormonal variability and more sleep disturbance than Profile 1 (p < 0.05). CONCLUSIONS: There is significant heterogeneity in cognition during perimenopause. While most women do not develop impairments, a significant minority experience weaknesses in verbal learning and memory. Profile analysis may identify at-risk populations and inform interventions.

The relationship between diabetes and depressive symptoms in men with or at risk of HIV infection.

OBJECTIVES: The aim of the study was to compare the prevalence of comorbid diabetes and depressive symptoms in men living with HIV (MLWH) with that in men without HIV infection and to determine associations between glycaemic control and depressive symptoms. METHODS: Participants included 920 MLWH and 840 men without HIV infection from the Multicenter AIDS Cohort Study (MACS) with available data regarding glycaemic status [categorized as normal for fasting blood glucose (FBG) < 100 mg/dL, prediabetes for FBG 100-125 mg/dL, and diabetes, defined by self-report, diabetes medication use or FBG ≥ 126 mg/dL on at least two consecutive visits, with diabetes classified as controlled if Hemoglobin A1c (HbA1C) < 7.5% and uncontrolled if HbA1C ≥ 7.5%]. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) score, with CES-D ≥ 16 scores classified as elevated depressive symptoms. A modified Poisson regression model with robust variance was used and adjusted for covariates including HIV serostatus. RESULTS: Compared to men without HIV infection, MLWH had a higher mean CES-D score, but a similar prevalence of diabetes (11.3% versus 12.8%, respectively; P = 0.33). The concomitant prevalence of diabetes and elevated depressive symptoms did not differ by HIV serostatus (P = 0.215). In an adjusted analysis, men with uncontrolled diabetes had a greater prevalence of depressive symptoms compared to men with normoglycaemia (prevalence ratio = 1.43; 95% confidence interval 1.11, 1.84). The association between glycaemic status and depressive symptoms did not differ by HIV serostatus (P = 0.22 for interaction). CONCLUSIONS: Both controlled and uncontrolled diabetes were independently associated with a greater prevalence of depressive symptoms, regardless of HIV serostatus. These results highlight the importance of identifying depression in people with diabetes.

Distinct risks, clinical characteristics and outcomes by age at time of HIV diagnosis.

OBJECTIVES: New HIV diagnoses in persons aged > 50 years (hereafter 'older persons') are becoming more common; the clinical features and outcomes of these older individuals are poorly described. METHODS: We conducted a retrospective cohort study of all new adult HIV diagnoses between October 1989 and December 2019 in southern Alberta, Canada. Differences in risk for HIV acquisition and screening, sociodemographic/clinical characteristics, and causes of death were compared between individuals younger and older than 50 years at the time of diagnosis. RESULTS: New HIV diagnoses in persons > 50 years old increased from 7% in 1990 to 18% in 2019. Risk for HIV acquisition and screening reasons differed by age. Heterosexual sex (29%) was the greatest risk factor among older persons, contrasting with male same sex activity in younger persons (51%) (P < 0.001). Illness was the most common indication for testing in older persons (47%), whereas younger persons were more likely to have requested testing (34%) (P < 0.001). Relationship status differed, with 33% of older persons being married to an opposite sex partner versus 12% in younger persons (P < 0.001). Although older persons had a lower mean nadir CD4 count (132 cells/µL) than younger persons (181 cells/µL) (P < 0.001), 80% of deaths between 2010 and 2019 in the older group were attributable to non-AIDS-related causes versus 47% in younger patients. Since 2000, AIDS-related deaths and potential years of life lost have declined for both age groups. CONCLUSION: The increase in new HIV diagnoses in persons aged > 50 years in southern Alberta suggests that older individuals require customized approaches for optimizing HIV diagnosis and treatment.

Menopausal symptoms, menopausal stage and cognitive functioning in black urban African women.

Objective: Studies, conducted largely in North America and Europe, demonstrate that menopausal symptoms and menopausal stage influence cognitive function. Here, we evaluate these associations in a large cohort of sub-Saharan African women, a population where these associations are understudied. We hypothesized that premenopausal women would show better cognitive performance than women later in the transition, and that menopausal symptoms would be inversely related to cognition.Methods: This cross-sectional study included 702 black urban South African women between the ages of 40 and 60 years from the Study of Women Entering and in Endocrine Transition. Participants completed the Symbol Digit Modalities Test, a measure of processing speed and incidental recall. Menopausal stage was ascertained using the Stages of Reproductive Aging Workshop+ 10 criteria and symptoms using the Menopause Rating Scale. Multivariable linear regression analyses were used to examine adjusted associations between menopausal stage and menopausal symptoms on cognitive performance.Results: In adjusted analyses, menopausal stage was not associated with processing speed (p = 0.35) or incidental recall (p = 0.64). However, more severe symptoms of hot flushes and anxiety were associated with slower processing speed (all p < 0.05), and more severe mood symptoms were associated with worse incidental recall (p = 0.008).Conclusion: Menopausal symptoms, but not menopausal stage, were associated with cognitive function in this cross-sectional study of sub-Saharan African women.

Patients' preimplantation genetic testing decision-making experience: an opinion on related psychological frameworks.

The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients' lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making' about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress' and `uncertainty' that patients endure as a result-apart from what decision they make-is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, 'intraindividual', 'interpersonal' and 'situational' factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients' well-being during their reproductive journey.

Persistent and aggressive interactions with the police: potential mental health implications.

AIMS: Little is known about the potential health impact of police encounters despite a ubiquitous police presence in many disadvantaged urban environments. In this paper, we assess whether persistent or aggressive interactions with the police are associated with poor mental health outcomes in a sample of primarily low-income communities of colour in Chicago. METHODS: Between March 2015 and September 2016, we surveyed 1543 adults in ten diverse Chicago communities using a multistage probability design. The survey had over 350 questions on health and social factors, including police exposure and mental health status. We use sex-stratified logistic regression to examine associations between persistent police exposure (defined as a high number of lifetime police stops) or aggressive police exposure (defined as threat or use of police force during the respondent's most recent police stop) and the presence of post-traumatic stress disorder (PTSD) or depressive symptoms. RESULTS: Men reporting a high number of lifetime police stops have three times greater odds of current PTSD symptoms compared with men who did not report high lifetime police stops (OR 3.1, 95% CI 1.3-7.6), after adjusting for respondent age, race/ethnicity, education, history of homelessness, prior diagnosis of PTSD and neighbourhood violent crime rate. Women reporting a high number of lifetime police stops have two times greater odds of current PTSD symptoms, although the results are not statistically significant after adjustment (OR 2.0, 95% CI 0.9-4.2). Neither persistent nor aggressive police exposure is significantly associated with current depressive symptoms in our sample. CONCLUSIONS: Our findings support existing preliminary evidence of an association between high lifetime police stops and PTSD symptoms. If future research can confirm as causal, these results have considerable public health implications given the frequent interaction between police and residents in disadvantaged communities in large urban areas.

The birth experience and subsequent maternal caregiving attitudes and behavior: a birth cohort study.

Optimal maternal caregiving is critical for children's healthy development, yet quality of maternal caregiving may be influenced by a negative birth experience. We examined whether the birth experience was associated with maternal caregiving attitudes and behavior throughout the first year. We conducted secondary analysis of the Avon Longitudinal Study of Parents and Children birth cohort on perinatal data. The birth experience was assessed using self-report data on level of support in labor. Maternal caregiving variables were self-report maternal attitudes at one and eight postnatal months, and observed maternal behavior at 12 postnatal months. Data were analyzed using multivariable logistic regression models adjusting for critical covariates at one (N = 4389), eight (N = 4580), and 12 (N = 842) postnatal months. Feeling supported in labor was associated with a report of "immediately falling in love" with one's baby after birth, surveyed at 1 month (adjusted OR 1.41 [95% CI 1.20-1.65]), and with more positive parenting scores at 8 months (adjusted OR 1.56 [95% CI 1.36-1.79]), but not with more positive observed maternal behavior at 12 months. Additional risk factors were identified. Our findings suggest that we may be able to modify the risk of poor postnatal maternal caregiving by supporting women in labor and facilitating a positive birth experience.

Increased complications in geriatric patients with a fracture of the hip whose postoperative weight-bearing is restricted: an analysis of 4918 patients.

AIMS: The aims of this study were to evaluate the incidence of postoperatively restricted weight-bearing and its association with outcome in patients who undergo surgery for a fracture of the hip. PATIENTS AND METHODS: Patient aged > 60 years undergoing surgery for a hip fracture were identified in the 2016 National Surgical Quality Improvement Program (NSQIP) Hip Fracture Targeted Procedure Dataset. Analysis of the effect of restricted weight-bearing on adverse events, delirium, infection, transfusion, length of stay, return to the operating theatre, readmission and mortality within 30 days postoperatively were assessed. Multivariate regression analysis was used to adjust for confounding demographic, comorbid and procedural characteristics. RESULTS: Of the 4918 patients who met inclusion criteria, 3668 (63.53%) were allowed to weight-bear as tolerated postoperatively. Controlling for patient and procedural factors, multivariate odds of any adverse event, major adverse event, delirium, infection, transfusion, length of stay ≥ 75th percentile (six days) and mortality within 30 days were all higher in patients with weight-bearing restrictions. Notably, there were no differences for thromboembolic events, return to the operating theatre or readmission within 30 days between the groups. CONCLUSION: Elderly patients with a fracture of the hip with postoperative weight-bearing restrictions have a significantly greater risk of developing most adverse events compared with those who are encouraged to weight-bear as tolerated. These findings emphasize the importance of immediate weight-bearing as tolerated to optimize the outcome in these frail patients; however nearly 25% of surgeons fail to meet this evidence-based guideline. Cite this article: Bone Joint J 2018;100-B:1377-84.

Verbal and spatial working memory among drug-using HIV-infected men and women.

Working memory (WM) is a critical component of many neurocognitive functions. The literature has demonstrated consistently that WM impairment is more frequent and severe among substance-dependent individuals (SDIs) infected with HIV compared with uninfected SDIs; however, the SDIs who participated in these previous studies were primarily male. There are few published data on WM performance among HIV+ women with or without substance use disorders, and essentially no direct comparisons of WM performance between HIV+ men and women, regardless of substance use. We investigated potential sex and serostatus effects on WM among a sample of 360 SDIs (114 with HIV; 66% female) verified abstinent from alcohol and drugs of abuse at testing and generally comparable on substance use and comorbid characteristics. Participants were tested with the n-back task, a well-established WM measure that is sensitive to HIV-associated cognitive impairment. HIV+ men and women performed spatial and verbal versions of the n-back significantly less accurately compared with HIV- participants. Women showed slower response times compared with men on both versions, regardless of HIV serostatus. Individuals dependent on cocaine showed faster RTs compared with non-dependent users, but this effect was not apparent among opioid- or alcohol-dependent groups. Findings on n-back accuracy are consistent with our previous proposal that WM impairment represents a signature deficit among HIV+ SDIs; however, WM impairment appears less common among HIV+ women without a substance use history. The pattern of sex differences in response speed but serostatus effects on response accuracy is comparable to a recent report by our group of sex differences in learning speed but serostatus effects on delayed recall.

Aseptic revision total hip arthroplasty in the elderly : quantifying the risks for patients over 80 years old.

AIMS: The aim of this study was to compare the rate of perioperative complications following aseptic revision total hip arthroplasty (THA) in patients aged ≥ 80 years with that in those aged < 80 years, and to identify risk factors for the incidence of serious adverse events in those aged ≥ 80 years using a large validated national database. PATIENTS AND METHODS: Patients who underwent aseptic revision THA were identified in the 2005 to 2015 National Surgical Quality Improvement Program (NSQIP) database and stratified into two age groups: those aged < 80 years and those aged ≥ 80 years. Preoperative and procedural characteristics were compared. Multivariate regression analysis was used to compare the risk of postoperative complications and readmission. Risk factors for the development of a serious adverse event in those aged ≥ 80 years were characterized. RESULTS: The study included 7569 patients aged < 80 years and 1419 were aged ≥ 80 years. Multivariate analysis showed a higher risk of perioperative mortality, pneumonia, urinary tract infection and the requirement for a blood transfusion and an extended length of stay in those aged ≥ 80 years compared with those aged < 80 years. Independent risk factors for the development of a serious adverse event in those aged ≥ 80 years include an American Society of Anesthesiologists score of ≥ 3 and procedures performed under general anaesthesia. CONCLUSION: Even after controlling for patient and procedural characteristics, aseptic revision THA is associated with greater risks in patients aged ≥ 80 years compared with younger patients. This is important for counselling and highlights the need for medical optimization in these vulnerable patients. Cite this article: Bone Joint J 2018;100-B:143-51.

Review of patient decision-making factors and attitudes regarding preimplantation genetic diagnosis.

The increasing technical complexity and evolving options for repro-genetic testing have direct implications for information processing and decision making, yet the research among patients considering preimplantation genetic diagnosis (PGD) is narrowly focused. This review synthesizes the literature regarding patient PGD decision-making factors, and illuminates gaps for future research and clinical translation. Twenty-five articles met the inclusion criteria for evaluating experiences and attitudes of patients directly involved in PGD as an intervention or considering using PGD. Thirteen reports were focused exclusively on a specific disease or condition. Five themes emerged: (1) patients motivated by prospects of a healthy, genetic-variant-free child, (2) PGD requires a commitment of time, money, energy and emotions, (3) patients concerned about logistics and ethics of discarding embryos, (4) some patients feel sense of responsibility to use available technologies, and (5) PGD decisions are complex for individuals and couples. Patient research on PGD decision-making processes has very infrequently used validated instruments, and the data collected through both quantitative and qualitative designs have been inconsistent. Future research for improving clinical counseling is needed to fill many gaps remaining in the literature regarding this decision-making process, and suggestions are offered.

Effects of sex and HIV serostatus on spatial navigational learning and memory among cocaine users.

Spatial learning and memory are critically dependent on the integrity of hippocampal systems. Functional MRI and neuropathological studies show that hippocampal circuitry is prominently affected among HIV-seropositive individuals, but potential spatial learning and memory deficits have not been studied in detail in this population. We investigated the independent and interactive effects of sex and HIV serostatus on performance of a spatial learning and memory task in a sample of 181 individuals with a history of cocaine dependence. We found that men showed faster times to completion on immediate recall trials compared with women and that delayed recall was significantly poorer among HIV-infected compared with HIV-uninfected participants. Additionally, a sex × serostatus effect was found on the total number of completed learning trials. Specifically, HIV-infected men successfully completed more learning trials compared with HIV-infected women. Results are discussed in the context of recent reports of sex and HIV serostatus effects on episodic memory performance.

Design of a Mobile Application for Transfusion Medicine.

One of the most frequent error in transfusion medicine is the failure in verifying the patient's identity prior to transfusion. This paper describes the design and development of a Mobile Application (MA) for transfusion medicine. The app uses barcode and QR reading technology for the verification of the patient's identity and the administration of blood components when making a blood transfusion. Physicians, developers, technicians of transfusion medicine and a User Centered Design team participated in the design. The inclusion of end users was fundamental to get full representativeness of their workflow. The project was based on agile methodologies of project management and software development.

Childbirth and symptoms of postpartum depression and anxiety: a prospective birth cohort study.

We investigated associations between aspects of childbirth and elevated postpartum symptoms of depression and anxiety. We employed secondary analysis of perinatal data (N = 4657-4946) from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariable logistic regression models (adjusted for covariates) examined predictors of elevated symptoms of postpartum depression and anxiety. Predictors included the following: type of delivery (normal physiological vs. interventive non-physiological), immediate postpartum complications, and maternal perception of the recent birth experience. The Edinburgh Postnatal Depression Scale assessed elevated symptoms of depression (score ≥ 13), and the Crown-Crisp Experiential Index assessed elevated symptoms of anxiety (score ≥ 9) at 2 and 8 months after delivery. A more negative perception of the recent birth experience was associated with elevated symptoms of anxiety at 2 months [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.25-1.85] and 8 months (OR 1.30, 95 % CI 1.06-1.60) postpartum but was not associated with elevated symptoms of depression at either time point. Type of delivery (physiological vs. non-physiological) and immediate postpartum complications were not associated with elevated symptoms of depression or anxiety. Our findings suggest that improving women's childbirth experience may decrease the likelihood of postpartum anxiety, but not postpartum depression.

The uncertainty of predicting intact anterior cruciate ligament degeneration in terms of structural properties using T(2)(*) relaxometry in a human cadaveric model.

The combination of healing anterior cruciate ligament (ACL) volume and the distributions of T2(*) relaxation times within it have been shown to predict the biomechanical failure properties in a porcine model. This MR-based prediction model has not yet been used to assess ligament degeneration in the aging human knee. Using a set of 15 human cadaveric knees of varying ages, we obtained in situ MR measures of volume and T2(*) of the intact ACL and then related these MR variables to biomechanical outcomes (maximum and yield loads, linear stiffness) obtained via ex vivo failure testing. Using volume in conjunction with the median T2(*) value, the multiple linear regression model did not predict maximum failure load for the intact human ACL; R(2)=0.23, p=0.200. Similar insignificant results were found for yield load and linear stiffness. Naturally restricted distributions of the intact ligament volume and T2(*) (demonstrated by the respective Z-scores) in an older cadaveric population were the likely reason for the insignificant results. These restricted distributions may negatively affect the ability to detect a correlation when one exists. Further research is necessary to understand the relationship of MRI variables and ligament degeneration. While this study failed to find a significant prediction of human biomechanical outcome using these MR variables, with further research, an MR-based approach may offer a tool to longitudinally assess changes in cruciate ligament degradation.

Neonatal intensive care unit: predictive models for length of stay.

OBJECTIVE: Hospital length of stay (LOS) is important to administrators and families of neonates admitted to the neonatal intensive care unit (NICU). A prediction model for NICU LOS was developed using predictors birth weight, gestational age and two severity of illness tools, the score for neonatal acute physiology, perinatal extension (SNAPPE) and the morbidity assessment index for newborns (MAIN). STUDY DESIGN: Consecutive admissions (n=293) to a New England regional level III NICU were retrospectively collected. Multiple predictive models were compared for complexity and goodness-of-fit, coefficient of determination (R (2)) and predictive error. The optimal model was validated prospectively with consecutive admissions (n=615). Observed and expected LOS was compared. RESULT: The MAIN models had best Akaike's information criterion, highest R (2) (0.786) and lowest predictive error. The best SNAPPE model underestimated LOS, with substantial variability, yet was fairly well calibrated by birthweight category. LOS was longer in the prospective cohort than the retrospective cohort, without differences in birth weight, gestational age, MAIN or SNAPPE. CONCLUSION: LOS prediction is improved by accounting for severity of illness in the first week of life, beyond factors known at birth. Prospective validation of both MAIN and SNAPPE models is warranted.

Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants.

OBJECTIVE: Dietary carotenoids (lutein, lycopene and ß-carotene) may be important in preventing or ameliorating prematurity complications. Little is known about carotenoid status or effects of supplementation. STUDY DESIGN: This randomized controlled multicenter trial compared plasma carotenoid levels among preterm infants (n=203, <33 weeks gestational age) fed diets with and without added lutein, lycopene and ß-carotene with human milk (HM)-fed term infants. We assessed safety and health. RESULT: Plasma carotenoid levels were higher in the supplemented group at all time points (P<0.0001) and were similar to those of term HM-fed infants. Supplemented infants had lower plasma C-reactive protein (P<0.001). Plasma lutein levels correlated with the full field electroretinogram-saturated response amplitude in rod photoreceptors (r=0.361, P=0.05). The supplemented group also showed greater rod photoreceptor sensitivity (least squares means 6.1 vs 4.1; P<0.05). CONCLUSION: Carotenoid supplementation for preterm infants raises plasma concentrations to those observed in HM-fed term infants. Carotenoid supplementation may decrease inflammation. Our results point to protective effects of lutein on preterm retina health and maturation.