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1.
Clin Endocrinol (Oxf) ; 100(5): 477-485, 2024 May.
Article in English | MEDLINE | ID: mdl-38462996

ABSTRACT

OBJECTIVE: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. DESIGN AND PARTICIPANTS: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. MEASUREMENTS: We analysed questionnaires that had complete demographic data. RESULTS: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. CONCLUSIONS: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires.


Subject(s)
Hypothyroidism , Pregnancy , Humans , Female , Australia , Hypothyroidism/drug therapy , Thyroid Hormones/therapeutic use , Thyroxine/therapeutic use , Triiodothyronine/therapeutic use , Surveys and Questionnaires , Thyrotropin/therapeutic use
2.
J Community Health ; 49(1): 70-77, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37450091

ABSTRACT

Providing family members of individuals with opioid use disorders (OUD) naloxone is a cost-effective way to prevent overdose deaths. However, misconceptions and negative attitudes towards naloxone hinder family engagement with naloxone programs. This study examines factors associated with knowledge and attitudes toward naloxone among adults with close family members who misused opioids. Adults with family members (parent, step-parent, child, spouse, sibling, or step-sibling) who misused opioids (N = 299) completed a web-based survey. Participants were recruited through treatment providers, community groups, and social media. Surveys assessed naloxone knowledge, attitudes toward overdose response, demographics, completion of naloxone training, attitude toward medications for OUD, and family members' overdose history. Multiple regression was used to identify factors associated with naloxone knowledge (Model 1) and attitudes toward overdose response (Model 2). A graduate degree (B = .35, p < .003) and a history of overdose (B = 0.21, p = .032) were associated with greater naloxone knowledge. Age (B = .11, p < .001), race/ethnicity (B = -1.39, p = .037), naloxone training (B = 2.70, p < .001), and more positive attitude toward medications for OUD (B = 1.50, p = .003) were associated with attitudes toward overdose response. Family members are potential allies in reducing drug overdose deaths, and families may need broader education about naloxone. Awareness of previous overdose was associated with greater naloxone knowledge. Findings related to race/ethnicity suggest the need to reach family members of minoritized racial groups to provide access to naloxone training. Findings point to where education and distribution efforts may focus on increasing knowledge and improving attitudes among those closest to people with OUD.


Subject(s)
Drug Overdose , Opioid-Related Disorders , Adult , Child , Humans , Analgesics, Opioid/therapeutic use , Drug Overdose/drug therapy , Drug Overdose/prevention & control , Family , Health Knowledge, Attitudes, Practice , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy
3.
Health Commun ; 39(3): 429-438, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36654526

ABSTRACT

A growing body of research demonstrates the role of language in stigma toward nonmedical opioid use (NMOU). Terms like "substance abuser" perpetuate stereotypes and evoke punitive judgments. This study examines how affected family members (AFMs) communicate stigma when discussing their loved one's NMOU. Semi-structured interviews were conducted with 34 adults with a close family member with a history of NMOU. An iterative approach was used to analyze instances when stigmatizing terms or messages were used. AFMs described people engaged in NMOU as underweight, "dirty," or "nodding off," and often labeled these individuals "addicts" or opioid "abusers." Responsibility for the NMOU was attributed to both internal (e.g. choice) and external (e.g. brain disease) factors. People engaged in NMOU were linked to physical danger, resource threats, and threats to the family members' reputation and relationships. While most stigma messages related to the person engaged in NMOU, stigmatizing messages directed toward AFMs also emerged; family members labeled "enablers" were judged, blamed, and described as a threat to the person engaged in NMOU. Although AFMs expressed care and desire to support their loved ones, they often conveyed stigma in their language choices. This language among AFMs may reflect internalized stigma. Increased efforts are needed to help AFMs cope with the challenges of a loved one's NMOU and identify effective ways to support their loved one. One way AFMs can support their loved one is by using more inclusive, person-first language.


Subject(s)
Analgesics, Opioid , Opioid-Related Disorders , Adult , Humans , Social Stigma , Family , Communication
4.
Matern Child Health J ; 27(8): 1293-1300, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37000382

ABSTRACT

INTRODUCTION: Adverse Childhood Experiences (ACEs) are associated with a range of negative physical and mental health outcomes, yet there is limited research focused on the effect of ACEs on stress responses during pregnancy. Expectant mothers experience an increase in cortisol levels as pregnancy progresses, with this increase having important implications for fetal and early infant development. Little is known about the impact of ACEs on maternal cortisol levels. This study explored the relationship between maternal ACEs and cortisol response among expectant mothers nearing or in the third trimester of pregnancy. METHODS: 39 expectant mothers were exposed to a Baby Cry Protocol via an infant simulator, with salivary cortisol collected at five points in time (N = 181). Stepwise, multilevel model creation resulted in a random intercept and random slope model with an interaction term for total number of ACEs and week of pregnancy. RESULTS: The repeated measures data showed that cortisol levels decreased across collection times, from arrival at the lab, through the Baby Cry Protocol, to recovery. Predictive margins for the interaction term showed that while exposure to a greater number of ACEs was associated with higher cortisol levels early in the third trimester, the expected increase in cortisol late in pregnancy was blunted for expectant mothers who were exposed to a greater number of ACEs. DISCUSSION: These findings findings suggest the importance of ACEs screening and intervention efforts as part of prenatal care.


Subject(s)
Adverse Childhood Experiences , Hydrocortisone , Female , Pregnancy , Child , Infant , Humans , Stress, Psychological , Mothers/psychology , Pregnancy Trimester, Third
5.
Health Soc Work ; 48(4): 231-239, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37616562

ABSTRACT

Substance use rates are higher among transgender and gender-diverse people than cisgender people. Rates of substance use are also higher among young adults compared with other age groups. However, little research examines substance use among transgender and gender-diverse young adults. This study examines factors associated with binge drinking and cannabis use among transgender and gender-diverse young adults in Michigan. Participants (N = 78; ages 18-25) completed an online survey that included demographics and substance use and related characteristics. Race, stimulant misuse, and sedative misuse were associated with more frequent binge drinking. Older age and past-year pain reliever misuse were associated with less frequent cannabis use. Past-year stimulant use and using cannabis alone were associated with more frequent cannabis use. These findings suggest that additional marginalized identities may increase the risk for maladaptive substance use. Future research should examine substance use behaviors and correlates to inform interventions among this population.


Subject(s)
Binge Drinking , Cannabis , Substance-Related Disorders , Transgender Persons , Humans , Young Adult , Adolescent , Adult , Michigan/epidemiology , Binge Drinking/epidemiology
6.
Drug Metab Dispos ; 2022 May 30.
Article in English | MEDLINE | ID: mdl-35636770

ABSTRACT

The utilization of in vitro data to predict drug pharmacokinetics (PK) in vivo has been a consistent practice in early drug discovery for decades. However, its success is hampered by mispredictions attributed to uncharacterized biological phenomena/experimental artifacts. Predicted drug clearance (CL) from experimental data (i.e. hepatocyte intrinsic clearance: CLint, fraction unbound in plasma: fu,p) is often systematically underpredicted using the well-stirred model (WSM). The objective of this study was to evaluate using empirical scalars in the WSM to correct for CL mispredictions. Drugs (N=28) were used to generate numerical scalars on CLint (α), and fu,p (ß) to minimize the error (AAFE) for CL predictions. These scalars were validated using an additional dataset (N=28 drugs) and applied to a non-redundant AstraZeneca (AZ) dataset available in the literature (N=117 drugs) for a total of 173 compounds. CL predictions using the WSM were improved for most compounds using an α value of 3.66 (~64%<2-fold) compared to no scaling (~46%<2-fold). Similarly, using a ß value of 0.55 or combination of α and ß scalars (values of 1.74 and 0.66, respectively) resulted in a similar improvement in predictions (~64%<2-fold and ~65%<2-fold, respectively). For highly bound compounds (fu,p{less than or equal to}0.01), AAFE was substantially reduced across all scaling methods. Using the ß scalar alone or a combination of α and ß appeared optimal; and produce larger magnitude corrections for highly-bound compounds. Some drugs are still disproportionally mispredicted, however the improvements in prediction error and simplicity of applying these scalars suggests its utility for early-stage CL predictions. Significance Statement In early drug discovery, prediction of human clearance using in vitro experimental data plays an essential role in triaging compounds prior to in vivo studies. These predictions have been systematically underestimated. Here we introduce empirical scalars calibrated on the extent of plasma protein binding that appear to improve clearance prediction across multiple datasets. This approach can be used in early phases of drug discovery prior to the availability of pre-clinical data for early quantitative predictions of human clearance.

7.
Clin Endocrinol (Oxf) ; 97(5): 634-642, 2022 11.
Article in English | MEDLINE | ID: mdl-35319116

ABSTRACT

OBJECTIVE: The role of the anti-Müllerian hormone (AMH) as an indicator of physical and reproductive health in men is unclear. We assessed the relationships between AMH and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and metabolic parameters, in a cohort of expectant fathers. DESIGN: ORIGINS Project prospective cohort study. SETTING: Community-dwelling men. PARTICIPANTS: Partners of pregnant women attending antenatal appointments. MAIN OUTCOME MEASURES: Serum AMH, FSH, LH, testosterone, and metabolic parameters. RESULTS: In 485 expectant fathers, median age 33 years, median AMH was 40 pmol/L (quartiles 29, 56). AMH was inversely correlated with FSH, age, and body mass index (BMI) (correlation coefficients: -.32, -.24, and -.17 respectively). The age association was nonlinear, with peak AMH between 20 and 30 years, a decline thereafter, and somewhat steady levels after 45 years. The inverse association of AMH with FSH was log-linear and independent of age and BMI (ß: -.07, SE: 0.01, p < .001). AMH was inversely correlated with waist circumference and directly associated with sex hormone-binding globulin. Testosterone was moderately correlated with AMH (correlation coefficient: .09, ß: .011, SE: 0.004, p = .014): this association was mediated by an inverse relationship with BMI (mediated proportion 0.49, p < .001). CONCLUSIONS: In reproductively active men, lower AMH is a biomarker for advancing age, and for poorer metabolic and reproductive health. The inverse association between AMH and FSH is independent of age and BMI, whereas the association of AMH and testosterone is mediated via BMI. The utility of AMH to predict reproductive and cardiometabolic outcomes in men warrants further investigation.


Subject(s)
Anti-Mullerian Hormone , Sex Hormone-Binding Globulin , Adiposity , Adult , Biomarkers , Fathers , Female , Follicle Stimulating Hormone , Humans , Luteinizing Hormone , Male , Obesity , Obesity, Abdominal , Pregnancy , Prospective Studies , Testosterone , Young Adult
8.
Neuropsychol Rehabil ; 32(3): 407-428, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33081575

ABSTRACT

Inappropriate sexual behaviours (ISX) are challenging clinical sequelae of acquired brain injury (ABI). Limited evidence exists about treatment approaches, with few case studies published to date. This study reports an exploratory clinical trial of community-based behaviour support interventions as a treatment approach to ISX after ABI. From routine referrals to a state-wide service specializing in challenging behaviours after ABI, a cohort (n = 24) displaying ISXs were selected. The interventions addressed multiple behavioural domains, and used a variety of approaches including environmental change, psychoeducation, and specific behavioural techniques. These approaches targetted change in the person with ABI, support personnel, or other environmental domains. Behaviour data were collected using the Overt Behaviour Scale (OBS) at baseline, closure and follow-up. Visual inspection and multilevel models were used to analyse the data. For the sample as a whole, there was a significant decline in ISXs from baseline to closure that was maintained at follow-up. Results at an individual level are also presented. Specificity of the intervention was demonstrated by comparison with concurrent challenging behaviours (aggression, perseveration, absconding) which showed no significant change over the same three time points. The results demonstrate the potential efficacy of community-based behaviour support interventions in treating ISXs after ABI.


Subject(s)
Behavior Therapy , Brain Injuries , Aggression , Brain Injuries/complications , Cohort Studies , Humans , Sexual Behavior
9.
Infant Ment Health J ; 43(2): 311-327, 2022 03.
Article in English | MEDLINE | ID: mdl-34879170

ABSTRACT

Few studies have examined whether maternal caregiving representations are associated with maternal reflective functioning (MRF), especially when MRF is evaluated longitudinally beginning in pregnancy. This study addresses this gap by evaluating whether prenatal and postnatal MRF are associated with mothers' caregiving representations assessed at 7 months postpartum, and by exploring theoretically unexpected MRF scores in each of the representational categories. Forty-seven mothers were recruited during their last trimester of pregnancy from an obstetrics clinic at a university hospital located in a large mid-western city in the United States. During pregnancy, mothers completed the Pregnancy Interview, and at 7 months postpartum they completed the Parent Development Interview (PDI) and the Working Model of the Child Interview. Results indicate that higher prenatal and postnatal MRF increased the odds of being classified as balanced versus disengaged. At 7 months, MRF also increased the odds of being balanced vs. distorted. Ten mothers who were classified as balanced or distorted had unexpected prenatal MRF scores, and six mothers had unexpected MRF scores when representations were assessed concurrently. Mothers classified as balanced with low MRF scores tended to have a low level of education, whereas mothers classified as distorted with high MRF scores had responses that were hostile, helpless, and role-reversed.


Pocos estudios han examinado el hecho de si las representaciones maternas acerca del cuidado están asociadas con el funcionamiento reflexivo materno (MRF), especialmente cuando MRF se evalúa longitudinalmente comenzando en el embarazo. Este estudio aborda este vacío por medio de evaluar si el MRF prenatal y postnatal está asociado con las representaciones que las madres tienen de prestar el cuidado evaluadas a los 7 meses después del parto, y por medio de explorar teoréticamente los puntajes no esperados de MRF en cada categoría representativa. Se reclutaron cuarenta y siete madres durante su último trimestre de embarazo del hospital de una universidad localizado en una ciudad del medio oeste de los Estados Unidos. Durante el embarazo, las madres completaron la Entrevista de Embarazo y a los 7 meses después del parto ellas completaron la Entrevista del Desarrollo del Progenitor y el Modelo de Trabajo de la Entrevista del Niño. Los resultados indican que el más alto MRF prenatal y postnatal también aumentó las posibilidades de ser clasificada como equilibrada vs. indiferente. A los 7 meses, el MRF también aumentó las posibilidades de ser equilibrada vs. distorsionada. Diez madres a quienes se les clasificó como equilibradas o distorsionadas tuvieron puntajes de MRF prenatales no esperados, y seis madres tuvieron no esperados puntajes de MRF cuando las representaciones fueron evaluadas al mismo tiempo. Las madres a quienes se les clasificó como equilibradas con bajos puntajes de MRF tendían a tener un nivel bajo de educación, mientras que las madres a quienes se les clasificó como distorsionadas con puntajes altos de MRF tuvieron respuestas que eran hostiles, indefensas y de inversión de papeles.


Peu d'études ont examiné si les représentations du soin maternel sont liées au fonctionnement réflectif maternel (abrégé ici selon l'anglais maternal reflective functioning, soit MRF), surtout lorsque le MRF est évalué de manière longitudinale à commencer par la grossesse. Cette étude porte sur cet écart en évaluant si le MRF prénatal et postnatal est lié aux représentations du soin des mères évalué à 7 mois postpartum, et en explorant des scores MRF théoriquement inattendus dans chacune des catégories représentationnelles. Quarante-sept mères ont été recrutées durant leur dernier trimestre de grossesse dans un CHU situé dans une grande ville du centre des Etats-Unis. Durant la grossesse les mères ont passé l'Entretien de Grossesse et à 7 mois postpartum elles ont passé l'Entretien du Développement du Parent et le Modèle de Travail de l'Entretien de l'Enfant. Les résultats indiquent qu'un MRF prénatal et postnatal élevé augmentait les chances d'être classé comme équilibrée par rapport à désengagée. A 7 mois, le MRF augmentait aussi les chances d'être équilibrée par rapport à faussée. Dix mères qui ont été classées comme étant équilibrées ou faussées avaient des scores de MRF prénatal inattendus et six mères avaient des scores de MRF inattendu quand les représentations étaient évaluées en même temps. Les mères classées comme équilibrées avec des scores de MRF bas tendaient à avoir un niveau d'éducation plus bas, alors que les mères classées comme faussées avec des scores de MRF élevés ont fait preuve de réactions qui étaient hostiles, désemparées et de rôle inversé.


Subject(s)
Mothers , Parents , Child , Educational Status , Emotions , Female , Humans , Infant , Mother-Child Relations , Object Attachment , Postpartum Period , Pregnancy
10.
Calcif Tissue Int ; 107(3): 230-239, 2020 09.
Article in English | MEDLINE | ID: mdl-32638038

ABSTRACT

Identification of variants in the calcium-sensing receptor (CASR) gene is an important means of distinguishing between familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism. However, identification and bioinformatics analysis of genetic variants alone is now considered insufficient as definitive proof; additional functional assessment is required to diagnose FHH with certainty. We identified two novel variants, D433Y and C739Y, and one previously reported variant G509R in the CASR of four kindreds provisionally diagnosed with FHH and aimed to functionally characterise these variants to confirm the diagnosis. Variant receptors were cloned as FLAG-tagged constructs into the mammalian expression vector, pcDNA3.1. Wild type and variant receptor constructs were expressed in HEK293 cells and their expression assessed by Western blot analysis and their functionality analysed using an IP-One assay which measures myo-inositol 1-phosphate accumulation following CaSR activation. Western blot analysis showed that the D433Y receptor had diminished mature glycosylated receptor compared with wild type CaSR whereas the G509R receptor had a complete lack of mature receptor. The C739Y receptor was consistently overexpressed. Functional assessment showed the D433Y receptor to be mildly inactivating at physiological calcium concentrations whereas the G509R receptor was inactive at all calcium concentrations. By contrast, the C739Y variant was activating compared to wild type receptor which is inconsistent with it causing FHH. We conclude that functional assessment of CaSR variants using the IP-One assay was useful in the investigation of suspected FHH probands, confirming the D433Y and G509R variants as likely pathogenic/pathogenic, but dismissing the C739Y variant as causing FHH.


Subject(s)
Hypercalcemia , Receptors, Calcium-Sensing , Calcium , HEK293 Cells , Humans , Hypercalcemia/congenital , Hypercalcemia/genetics , Mutation , Receptors, Calcium-Sensing/genetics
11.
J Nerv Ment Dis ; 208(11): 870-875, 2020 11.
Article in English | MEDLINE | ID: mdl-32773612

ABSTRACT

Expressed emotion has been robustly associated with negative mental health outcomes. Understanding correlates of expressed emotion by family members of individuals with opioid use disorder is important, as this group faces high levels of stress and can play an important role in their loved ones' treatment. Thus, immediate family members of individuals who sought treatment for opioid problems (N = 195) completed a web-based survey that included measures of expressed emotion, self-stigma, social support, and demographic characteristics. Multiple linear regression analyses were conducted to examine correlates of two types of expressed emotion-criticism and emotional overinvolvement. Results indicated that higher self-stigma and lower social support were significantly associated with higher emotional overinvolvement. Higher self-stigma and having experienced debt related to a family member's opioid use were associated with higher criticism. Thus, self-stigma and financial burden may exacerbate likelihood of expressed emotion, whereas social support may buffer against expressed emotion.


Subject(s)
Expressed Emotion , Family/psychology , Opioid-Related Disorders/psychology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Opioid-Related Disorders/economics , Social Stigma , Social Support , Surveys and Questionnaires , Young Adult
12.
Neuropsychol Rehabil ; 30(3): 481-502, 2020 Apr.
Article in English | MEDLINE | ID: mdl-29882464

ABSTRACT

People with acquired brain injury (ABI) are overrepresented in prison populations across many countries. An effective service response to reduce this trend requires collaboration between the ABI and criminal justice (CJ) sectors. The Building Bridges project piloted a novel professional development model designed to increase cross-sectoral knowledge and collaboration between the ABI and CJ sectors. A total of 178 service providers from Victoria, Australia, participated in six professional development forums that included content about ABI, policing, disability and legal supports, and correctional/post-release services. Participants came from the disability, criminal justice, and health and community service sectors. Using a pre-test-post-test design with 6-month follow-up, data were obtained via a project-specific questionnaire evaluating knowledge and behaviour change among participants. Statistically significant gains in knowledge were shown at post-test and maintained at follow-up. Work-related behaviours addressing ABI/CJ issues had increased significantly within both sectors at follow-up compared to the 6 months prior to the forum. Carefully constructed professional forums improved cross-silo collaboration in the ABI/CJ sectors. This pilot project illustrates effective use of existing service resources, and highlights training as an important part of a raft of initiatives needed to address the overrepresentation of people with ABI in the CJ system.


Subject(s)
Brain Injuries , Criminal Law , Criminals , Disabled Persons , Education, Continuing , Health Knowledge, Attitudes, Practice , Health Services , Intersectoral Collaboration , Professional Competence , Adult , Brain Injuries/rehabilitation , Criminals/legislation & jurisprudence , Disabled Persons/legislation & jurisprudence , Disabled Persons/rehabilitation , Follow-Up Studies , Humans , Pilot Projects , Victoria
13.
Neurol Neurochir Pol ; 54(4): 312-322, 2020.
Article in English | MEDLINE | ID: mdl-32808273

ABSTRACT

AIM: To evaluate five illustrative cases and perform a literature review to identify and describe a working approach to adult-onset white matter diseases (WMD). STATE OF THE ART: Inherited WMD are a group of disorders often seen in childhood. In adulthood, progressive WMDs are rare, apart from the common nonspecific causes of hypertension and other cerebrovascular diseases. The pattern of WMDs on neuroimaging can be an important clue to the final diagnosis. Due to the adoption of a combined clinical-imaging-laboratory approach, WMD is becoming better recognised, in addition to the rapidly evolving field of genomics in this area. CLINICAL IMPLICATIONS: While paediatric WMDs have a well-defined and literature-based clinical-laboratory approach to diagnosis, adult-onset WMDs remain an important, pathologically diverse, radiographic phenotype, with different and distinct neuropathologies among the various subtypes of WMD. Adult-onset WMDs comprise a wide collection of both acquired and inherited aetiologies. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neurological complications are emerging, we are as yet unaware of it causing WMD outside of post-anoxic changes. It is important to recognise WMD as a potentially undefined acquired or genetic syndrome, even when extensive full genome testing reveals variants of unknown significance. FUTURE DIRECTIONS: We propose a combined clinical-imaging-laboratory approach to WMD and continued exploration of acquired and genetic factors. Adult-onset WMD, even given this approach, can be challenging because hypertension is often comorbid. Therefore, we propose that undiagnosed patients with WMD be entered into multicentre National Organisation for Rare Diseases registries to help researchers worldwide make new discoveries that will hopefully translate into future cures.


Subject(s)
Leukoencephalopathies/diagnosis , Leukoencephalopathies/etiology , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections , Humans , Pandemics , Pneumonia, Viral , SARS-CoV-2 , White Matter/pathology
14.
Hum Mol Genet ; 26(14): 2791-2802, 2017 07 15.
Article in English | MEDLINE | ID: mdl-28472463

ABSTRACT

Osteoporosis is a common and debilitating bone disease that is characterised by low bone mineral density, typically assessed using dual-energy X-ray absorptiometry. Quantitative ultrasound (QUS), commonly utilising the two parameters velocity of sound (VOS) and broadband ultrasound attenuation (BUA), is an alternative technology used to assess bone properties at peripheral skeletal sites. The genetic influence on the bone qualities assessed by QUS remains an under-studied area. We performed a comprehensive genome-wide association study (GWAS) including low-frequency variants (minor allele frequency ≥0.005) for BUA and VOS using a discovery population of individuals with whole-genome sequence (WGS) data from the UK10K project (n = 1268). These results were then meta-analysed with those from two deeply imputed GWAS replication cohorts (n = 1610 and 13 749). In the gender-combined analysis, we identified eight loci associated with BUA and five with VOS at the genome-wide significance level, including three novel loci for BUA at 8p23.1 (PPP1R3B), 11q23.1 (LOC387810) and 22q11.21 (SEPT5) (P = 2.4 × 10-8 to 1.6 × 10-9). Gene-based association testing in the gender-combined dataset revealed eight loci associated with BUA and seven with VOS after correction for multiple testing, with one novel locus for BUA at FAM167A (8p23.1) (P = 1.4 × 10-6). An additional novel locus for BUA was seen in the male-specific analysis at DEFB103B (8p23.1) (P = 1.8 × 10-6). Fracture analysis revealed significant associations between variation at the WNT16 and RSPO3 loci and fracture risk (P = 0.004 and 4.0 × 10-4, respectively). In conclusion, by performing a large GWAS meta-analysis for QUS parameters of bone using a combination of WGS and deeply imputed genotype data, we have identified five novel genetic loci associated with BUA.


Subject(s)
Osteoporosis/diagnostic imaging , Ultrasonography/methods , Absorptiometry, Photon , Adult , Aged , Aged, 80 and over , Bone Density , Calcaneus/diagnostic imaging , Female , Fractures, Bone/diagnostic imaging , Genome-Wide Association Study , Humans , Male , Middle Aged
15.
Neurocrit Care ; 30(2): 414-420, 2019 04.
Article in English | MEDLINE | ID: mdl-30357597

ABSTRACT

BACKGROUND/OBJECTIVE: Early mobilization of critically ill patients has been shown to improve functional outcomes. Neurosurgery patients with an external ventricular drain (EVD) due to increased intracranial pressure often remain on bed rest while EVD remains in place. The prevalence of mobilizing patients with EVD has not been described, and the literature regarding the safety and feasibility of mobilizing patients with EVDs is limited. The aim of our study was to describe the outcomes and adverse events of the first mobilization attempt in neurosurgery patients with EVD who participated in early functional mobilization with physical therapy or occupational therapy. METHODS: We performed a single-site, retrospective chart review of 153 patients who underwent placement of an EVD. Hemodynamically stable patients deemed appropriate for mobilization by physical or occupational therapy were included. Mobilization and activity details were recorded. RESULTS: The most common principal diagnoses were subarachnoid hemorrhage (61.4%) and intracerebral hemorrhage (17.0%) requiring EVD for symptomatic hydrocephalus. A total of 117 patients were mobilized (76.5%), and the median time to first mobilization after EVD placement in this group of 117 patients was 38 h. Decreased level of consciousness was the most common reason for lack of mobilization. The highest level of mobility on the patient's first attempt was ambulation (43.6%), followed by sitting on the side of the bed (30.8%), transferring to a bedside chair (17.1%), and standing up from the side of the bed (8.5%). No major safety events, such as EVD dislodgment, occurred in any patient. Transient adverse events with mobilization were infrequent at 6.9% and had no permanent neurological sequelae and were mostly headache, nausea, and transient diastolic blood pressure elevation. CONCLUSION: Early progressive mobilization of neurosurgical intensive care unit patients with external ventricular drains appears safe and feasible.


Subject(s)
Cerebral Hemorrhage/therapy , Early Ambulation/statistics & numerical data , Hydrocephalus/therapy , Subarachnoid Hemorrhage/therapy , Ventriculostomy/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/rehabilitation , Cerebral Hemorrhage/surgery , Early Ambulation/adverse effects , Feasibility Studies , Female , Humans , Hydrocephalus/etiology , Hydrocephalus/rehabilitation , Hydrocephalus/surgery , Male , Middle Aged , Retrospective Studies , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/rehabilitation , Subarachnoid Hemorrhage/surgery , Ventriculostomy/adverse effects , Young Adult
16.
J Biosoc Sci ; 51(3): 374-393, 2019 05.
Article in English | MEDLINE | ID: mdl-30350763

ABSTRACT

Despite the significant health benefits of breastfeeding for the mother and the infant, economic class and race disparities in breastfeeding rates persist. Support for breastfeeding from the father of the infant is associated with higher rates of breastfeeding initiation. However, little is known about the factors that may promote or deter father support of breastfeeding, especially in fathers exposed to contextual adversity such as poverty and violence. Using a mixed methods approach, the primary aims of the current work were to (1) elicit, using qualitative methodology, the worries, barriers and promotive factors for breastfeeding that expectant mothers and fathers identify as they prepare to parent a new infant, and (2) to examine factors that influence the parental breastfeeding intentions of both mothers and fathers using quantitative methodology. A sample (N=95) of expectant, third trimester mothers and fathers living in a low-income, urban environment in Midwestern USA, were interviewed from October 2013 to February 2015 about their infant feeding intentions. Compared with fathers, mothers more often identified the benefits of breastfeeding for the infant's health and the economic advantage of breastfeeding. Mothers also identified more personal and community breastfeeding support resources. Fathers viewed their own support of breastfeeding as important but expressed a lack of knowledge about the breastfeeding process and often excluded themselves from discussions about infant feeding. The results point to important targets for interventions that aim to increase breastfeeding initiation rates in vulnerable populations in the US by increasing father support for breastfeeding.


Subject(s)
Breast Feeding/psychology , Fathers/psychology , Intention , Mothers/psychology , Poverty , Pregnancy/psychology , Social Environment , Adult , Female , Humans , Infant , Infant, Newborn , Male , Midwestern United States , Pregnancy Trimester, Third , Prenatal Care , Sex Factors , Social Support
17.
Subst Abus ; 40(2): 185-193, 2019.
Article in English | MEDLINE | ID: mdl-30888262

ABSTRACT

Background: African American patients with opioid use disorder (OUD) have demonstrated poorer methadone maintenance treatment (MMT) outcomes compared with white patients. This issue is further complicated in urban settings, where African Americans experience high rates of poverty and publicly funded treatment. Despite interrelated factors that disadvantage African Americans, the literature focusing on this population is scant. To address this shortcoming, we conducted the first investigation of gender differences and gender-specific MMT outcome predictors among African Americans (or any racial minority population). This study provides gender-specific findings to improve African American MMT outcomes. Methods: We studied 211 African American patients (male: n = 137, 64.9%) at an urban, university-affiliated MMT clinic. We used existing intake data to assess baseline demographic, substance use, mental health, and interpersonal factors. Primary outcomes were 3-month drug+ (positive) urine drug screen (UDS) results and treatment retention. Results: Women were more likely (than men) to endorse histories of interpersonal violence, substance abuse in their social network, and mental health problems. Men reported a greater likelihood (than women) for early opioid-use onset and a lack of prior MMT. There were no gender differences in 3-month drug+ UDS or treatment retention. In multivariable analyses among women, no baseline factors predicted 3-month opioid+ UDS and physical abuse history predicted a higher proportion of 3-month cocaine+ UDS. Among men, primary injection opioid use and older age best predicted a higher proportion of 3-month cocaine+ UDS and parent substance abuse predicted shorter retention. In both gender-stratified analyses, higher proportions of 3-month opioid+ UDS and cocaine+ UDS predicted shorter retention. Conclusions: This study offers an analysis of gender differences in risk factors, MMT outcomes, and gender-specific predictors among African American patients. MMT clinics should tailor assessment and treatment protocols to address gender-specific needs.


Subject(s)
Analgesics, Opioid/therapeutic use , Black or African American , Methadone/therapeutic use , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Academic Medical Centers , Adult , Age of Onset , Ambulatory Care Facilities , Cocaine , Cocaine-Related Disorders/epidemiology , Female , Humans , Linear Models , Male , Mental Disorders/epidemiology , Middle Aged , Minority Health , Opioid-Related Disorders/epidemiology , Prognosis , Sex Factors , Social Networking , Substance Abuse Detection , Treatment Outcome , Urban Population , Violence/statistics & numerical data
18.
Neuropsychol Rehabil ; 29(5): 704-722, 2019 Jun.
Article in English | MEDLINE | ID: mdl-28532322

ABSTRACT

The objectives were to test the properties, via a psychometric study, of the Overt Behaviour Scale-Self-Report (OBS-SR), a version of the OBS-Adult Scale developed to provide a client perspective on challenging behaviours after acquired brain injury. Study sample 1 consisted of 37 patients with primary brain tumour (PBT) and a family-member informant. Sample 2 consisted of 34 clients with other acquired brain injury (mixed brain injury, MBI) and a service-provider informant. Participants completed the OBS-SR (at two time points), and the Awareness Questionnaire (AQ) and Mayo Portland Adaptability Inventory-III (MPAI-III) once; informants completed the OBS-Adult and AQ once only. PBT-informant dyads displayed "good" levels of agreement (ICC2,k = .74; OBS-SR global index). Although MBI-informant dyads displayed no agreement (ICC2,k = .22; OBS-SR global index), the sub-group (17/29) rated by clinicians as having moderate to good levels of awareness displayed "fair" agreement (ICC2,k = .58; OBS-SR global index). Convergent/divergent validity was demonstrated by significant correlations between OBS-SR subscales and MPAI-III subscales with behavioural content (coefficients in the range .36 -.61). Scores had good reliability across one week (ICC2,k = .69). The OBS-SR took approximately 15 minutes to complete. It was concluded that the OBS-SR demonstrated acceptable reliability and validity, providing a useful resource in understanding clients' perspectives about their behaviour.


Subject(s)
Brain Injuries/complications , Brain Injuries/psychology , Mental Disorders/diagnosis , Mental Disorders/etiology , Self Report , Adaptation, Psychological , Adult , Aged , Awareness , Correlation of Data , Female , Humans , Male , Middle Aged , Psychometrics , Reproducibility of Results , Retrospective Studies
19.
JAMA ; 322(7): 632-641, 2019 08 20.
Article in English | MEDLINE | ID: mdl-31429897

ABSTRACT

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.


Subject(s)
Autoimmune Diseases/diagnosis , Iodide Peroxidase/immunology , Pregnancy Complications/diagnosis , Premature Birth/etiology , Thyroid Diseases/diagnosis , Thyroid Function Tests , Adult , Autoantibodies/blood , Autoimmune Diseases/blood , Autoimmune Diseases/complications , Female , Gestational Age , Humans , Hypothyroidism/complications , Hypothyroidism/diagnosis , Infant, Newborn , Pregnancy , Pregnancy Complications/blood , Thyroid Diseases/blood , Thyroid Diseases/complications , Thyrotropin/blood , Thyroxine/blood
20.
Addict Res Theory ; 27(4): 294-304, 2019.
Article in English | MEDLINE | ID: mdl-31474814

ABSTRACT

Poor early relationship experiences during the first 16 years of life may negatively impact adults' capacity to establish and utilize social support (Suchman, McMahon, Slade, & Luthar, 2005). This is especially of concern for women with substance use disorders (SUD) for whom social support is associated with recovery maintenance and treatment retention (Gregoire & Snively, 2001). The purpose of this study was to examine the influence of early relationship experiences, specifically paternal and maternal warmth, on recovery related social support and personal network characteristics among African American (AA) and non-AA women in treatment for SUD. Data were collected from 254 women in substance abuse treatment, 146 AA and 108 non-AA. Ordinal logistic, Poisson or multiple linear regressions were fitted to predict the impact of maternal and paternal warmth during childhood on adult social network composition and recovery support. Greater maternal warmth was associated with greater recovery-specific social support for both AA (ß = 0.12) and non-AA (ß = 0.15) women. Paternal, but not maternal, warmth significantly predicted the number of social network members who supported recovery for non-AA women (AOR = 1.04), and number of network members who used drugs and alcohol for AA women (IRR = 0.99). Developmental experiences associated with fathers appear to affect different domains of adult functioning than those associated with mothers, and those effects are different for AA versus non-AA women. Attention to these differences may inform culturally relevant substance abuse prevention and treatment efforts.

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