Sexual distress is associated with a variety of negative outcomes. Unique contributors to sexual distress exist among transgender individuals. The current study examined the impacts of ...gender-affirming interventions (i.e., hormone therapy HT, gender-affirmation surgery GAS) and body satisfaction on sexual distress among 317 transgender adults recruited nationally to participate in an anonymous online survey. As expected, individuals who had received HT and/or GAS reported better body satisfaction compared to those who wanted these interventions but had not yet received them. Sexual distress did not differ by transition status. As hypothesized, time since transition began was positively associated with body satisfaction, and there was an indirect relationship between time since transition began and sexual distress through body satisfaction. These results replicated findings in the extant literature suggesting that body satisfaction is improved by GAS. Furthermore, this was the first study of which we are aware to examine the role of time since transition began with respect to body satisfaction and the resulting impact on sexual distress. Results from this study may have clinical implications that could help improve the gender-affirmation experience for transgender individuals.
Aims
There are no treatments for the extreme hyperphagia and obesity in Prader–Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine ...aminopeptidase 2 (MetAP2) inhibitor, beloranib.
Materials and Methods
Participants with PWS (12‐65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co‐primary endpoints were the changes in hyperphagia measured by Hyperphagia Questionnaire for Clinical Trials (HQ‐CT); possible score 0‐36 and weight by intention‐to‐treat. ClinicalTrials.gov registration: NCT02179151.
Results
One‐hundred and seven participants were included in the intention‐to‐treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ‐CT total score was greater in the 1.8 mg (mean difference −6.3, 95% CI −9.6 to −3.0;
P
= .0003) and 2.4 mg beloranib groups (−7.0, 95% CI −10.5 to −3.6;
P
= .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference − 8.2%, 95% CI −10.8 to −5.6;
P
< .0001) and 2.4 mg beloranib (−9.5%, 95% CI −12.1 to −6.8;
P
< .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib‐treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo.
Conclusions
MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia‐related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.
Objective
This study assessed the effect of 1‐year administration of diazoxide choline extended‐release tablet (DCCR) on hyperphagia and other complications of Prader‐Willi syndrome (PWS).
Methods
...The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open‐label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ‐CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety.
Results
DCCR administration resulted in significant improvements in HQ‐CT (mean SE −9.9 0.77, p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ‐CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment‐emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%).
Conclusions
DCCR administration to people with PWS was well tolerated and associated with broad‐ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.
Summary
Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival ...through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate‐induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011.
The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we ...have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as “GENE-related phenotype descriptor” (e.g., “CFTR-related cystic fibrosis”). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive ...domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = −.08 −.14, −.02) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults.
Summary
A growing population of long‐term survivors of myeloma is now accumulating the ‘late effects’ not only of myeloma itself, but also of several lines of treatment given throughout the course of ...the disease. It is thus important to recognise the cumulative burden of the disease and treatment‐related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long‐term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late‐effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted.
•Lifetime report of racial discrimination is associated with greater adverse gene expression 6-months following traumatic injury.•Higher levels of lifetime racial discrimination were associated with ...increased CTRA gene expression over time following injury, however, CTRA gene expression did not increase significantly for those reporting lower levels of racial discrimination.•Racial discrimination serves as chronic stressor that over time contributes to break down of biological stress responses resulting in greater inflammation and lowered immune response.
Up to 40 % of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and six-months (T2) post-injury, Black participants (N = 94) provided a blood specimen and completed assessments of lifetime racial discrimination and PTSD symptoms. Mixed effect linear models evaluated the relationship between change in CTRA gene expression and racial discrimination while adjusting for age, gender, body mass index (BMI), smoking history, heavy alcohol use history, and trauma-related variables (mechanism of injury, lifetime trauma). Results revealed that for individuals exposed to higher levels of lifetime racial discrimination, CTRA significantly increased between T1 and T2. Conversely, CTRA did not increase significantly over time in individuals exposed to lower levels of lifetime racial discrimination. Thus, racial discrimination appeared to lead to a more sensitized biological profile which was further amplified by the effects of a recent traumatic injury. These findings replicate and extend previous research elucidating the processes by which racial discrimination targets biological systems.
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