Health-related quality of life in women with primary ovarian insufficiency: a scoping review of the literature and implications for targeted interventions.

STUDY QUESTION: What is known about health-related quality of life (HR-QoL) in women with idiopathic primary ovarian insufficiency (POI)? SUMMARY ANSWER: Women with POI have a range of unmet psychosocial needs relating to three interrelated themes: 'diagnostic odyssey', 'isolation and stigma' and impaired 'ego integrity'. WHAT IS KNOWN ALREADY: Prior studies have reported increased depressive symptoms, diminished sexual function and altered body image/self-concept in women with POI. STUDY DESIGN, SIZE, DURATION: A systematic scoping review (11 databases) on HR-QoL in POI including published quantitative, qualitative and mixed-methods studies as well as unpublished gray literature (i.e. unpublished dissertations) through June, 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: After removing duplicates, 1244 articles underwent title and abstract review by independent reviewers. The remaining 72 relevant articles underwent dual full text review to determine inclusion criteria yielding 24 articles (100% concordance) for data extraction. Findings were summarized in tables by methodology and recurrent HR-QoL themes/sub-themes were mapped to define key aspects of HR-QoL in POI. Promoters of active coping were charted at the individual, interpersonal and healthcare system levels. Targets for tailored interventions supporting active coping and improved HR-QoL were mapped to the Theory of Planned Behavior (TPB). MAIN RESULTS AND THE ROLE OF CHANCE: Three interrelated themes affecting HR-QoL in POI emerged from the data synthesis. First, the theme 'diagnostic odyssey' comprised sub-themes of uncertainty, lack of control, knowledge gaps, discontinuous care and negative clinical interactions. The second theme 'isolation and stigma' included sub-themes of guilt, shame, concealment, feeling labeled as infertile, lack of social support and unsympathetic clinicians. The third theme, impaired 'ego integrity' captured sub-themes of decreased sexual function, altered body image, psychological vulnerability and catastrophizing. Targets promoting active coping at the individual (n = 2), interpersonal (n = 1) and healthcare system (n = 1) levels were mapped to the TPB to inform development of tailored interventions supporting active coping and improved HR-QoL in POI (i.e. narrative intervention, co-creating patient-facing materials, peer-to-peer support and provider resources). LIMITATIONS, REASONS FOR CAUTION: No studies using a POI-specific HR-QoL instrument were identified. No interventional studies aimed at improving HR-QoL in POI were identified. Only articles published in English were included in the study. WIDER IMPLICATIONS OF THE FINDINGS: Women with POI frequently have impaired HR-QoL related to the life-altering infertility diagnosis. The range of unmet psychosocial needs may be relevant for informing interventions for other populations with infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development 'Massachusetts General Hospital-Harvard Center for Reproductive Medicine' (1 P50 HD104224-01 NICHD). The authors have no conflicts to declare. REGISTRATION NUMBER: N/A.

Coping response and family communication of cancer risk in men harboring a BRCA mutation: A mixed methods study.

OBJECTIVE: Providing genetic counseling and genetic testing to at-risk blood relatives (cascade screening) is important for improving BRCA cancer outcomes. Intra-familial communication of risk is critical for cascade screening efforts yet relatively little is known about men's role in communicating BRCA risk. We sought to examine men's coping response to their BRCA status and intra-familial communication of risk to inform the development of tailored interventions that could promote cascade screening. METHODS: We employed a sequential mixed-methods design. First, we measured coping response (quantitative) using the Multidimensional Impact of Cancer Risk Assessment (MICRA). MICRA scores were compared between BRCA+ men, BRCA- men and BRCA+ women. Subsequently, we used template analysis to analyze qualitative interviews exploring coping and intra-familial communication of risk. The Theory of Planned Behavior (TPB) served as a guiding framework for identifying intervention targets. RESULTS: BRCA+ men (n = 36) had significantly higher levels of distress (p < 0.001), uncertainty (p < 0.001) and negative experiences (p < 0.05) compared to BRCA- male counterparts (n = 23). BRCA+ men had significantly lower distress (p < 0.001) and uncertainty (p < 0.001) than BRCA+ women (n = 406). Qualitative analysis of in-depth interviews with BRCA+ men (n = 35) identified promoters and barriers to active coping response and intra-familial communication of risk. Mapping results onto the TPB identified targets for tailoring person-centered approaches for men addressing beliefs/attitude, subjective norms, and perceived behavioral control. CONCLUSIONS: Men and women appear to have different coping responses to learning their BRCA status. Developing tailored (sex-based), theory informed interventions may help promote intra-familial communication of BRCA risk and support cascade screening.

Latinx individuals' knowledge of, preferences for, and experiences with prenatal genetic testing: a scoping review.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends prenatal genetic testing (PGT) be offered to all pregnant persons regardless of known risk factors. However, significant racial/ethnic differences exist regarding acceptance of PGT contributing to disparities. Latinas (Latinx), one of the fastest growing ethnic groups in the United States, have low PGT acceptance rates. This systematic scoping review aimed to provide a landscape of existing literature on Latinx individuals' knowledge of, preferences for, and experiences with prenatal and preconception genetic testing. Synthesizing the current state of the science may inform development of culturally tailored interventions to support high-quality PGT decisions (e.g., informed, aligned with a pregnant persons' values). METHODS: We conducted a structured, systematic literature search of published articles and gray literature in electronic databases (PubMed, PsycINFO, CINAHL, Medline, Embase, Eric, Social Services Abstracts, and PsycArticles). Articles in English published prior to March 2021 were retrieved relating to genetics, pregnancy, and Latina women. Articles underwent title, abstract and full-text review by independent investigators to assess inclusion and exclusion criteria. Risk of bias was evaluated by two investigators. Iterative thematic analysis was employed to group study findings into themes to identify possible targets for interventions. RESULTS: The search generated 5511 unique articles. After title screening, 335 underwent abstract review and subsequently 61 full-text review. Twenty-eight studies met inclusion criteria and 7 additional studies were included after reviewing reference lists. Three overarching themes emerged: genetic knowledge/literacy (26/35, 74%), provider (mis)communication/patient satisfaction (21/35, 60%), and cross-cultural beliefs (12/35, 34%). Studies indicate discordant patient-provider language (n = 5), miscommunication (n = 4), and lack of concordant decision-making (n = 4) pose barriers to high-quality PGT decisions. Immigration status (n = 1) and religious beliefs (n = 5) are additional factors influencing PGT decisions. CONCLUSIONS: Identified studies suggest that cultural and linguistic factors affect Latinx PGT decision-making. Latinx individual's comprehension and recall of PGT information is enhanced by culturally and linguistically concordant providers-suggesting that culturally-informed interventions may enhance PGT acceptability and support high-quality decisions. Future directions to surmount PGT disparities may include community health workers and cultural brokers to empower Latinx people to make informed decisions aligned with their values and preferences.

Significant racial, ethnic, and language disparities exist in prenatal genetic testing (PGT). Latina (Latinx) people, one of the fastest growing ethnic groups in the United States, have low acceptance rates of PGT. This scoping review provides a systematic search of the literature to better understand Latinx individuals' knowledge of, preferences for, and experiences with PGT. Eight electronic data bases were systematically searched and identified articles underwent title, abstract, full text, and reference review. Iterative thematic analysis was conducted to group article findings into themes. Thirty-five studies met inclusion criteria and three overarching themes were identified: genetic knowledge/literacy, provider (mis)communication/patient satisfaction, and cross-cultural beliefs. Findings indicate that discordant patient-provider decision making and language and patient provider miscommunication pose barriers to high-quality PGT decisions. Latinx individuals' understanding and recall of PGT information is improved when delivered in a culturally and linguistically concordant manner. This suggests culturally-informed interventions, including the use of community health workers or cultural brokers, may enhance PGT acceptability and support high quality pregnancy decisions.

Congenital Hypogonadotropic Hypogonadism with Anosmia and Gorlin Features Caused by a PTCH1 Mutation Reveals a New Candidate Gene for Kallmann Syndrome.

BACKGROUND: Two loci (CHD7 and SOX10) underlying Kallmann syndrome (KS) were discovered through clinical and genetic analysis of CHARGE and Waardenburg syndromes, conditions that include congenital anosmia caused by olfactory bulb (CA/OBs) defects and congenital hypogonadotropic hypogonadism (CHH). We hypothesized that other candidate genes for KS could be discovered by analyzing rare syndromes presenting with these signs. Study Design, Size, Duration: We first investigated a family with Gorlin-Goltz syndrome (GGS) in which affected members exhibited clinical signs suggesting KS. Participants/Materials, Methods: Proband and family members underwent detailed clinical assessment. The proband received detailed neuroendocrine evaluation. Genetic analyses included sequencing the PTCH1 gene at diagnosis, followed by exome analyses of causative or candidate KS/CHH genes, in order to exclude contribution to the phenotypes of additional mutations. Exome analyses in additional 124 patients with KS/CHH probands with no additional GGS signs. RESULTS: The proband exhibited CA, absent OBs on magnetic resonance imaging, and had CHH with unilateral cryptorchidism, consistent with KS. Pulsatile Gonadotropin-releasing hormone (GnRH) therapy normalized serum gonadotropins and increased testosterone levels, supporting GnRH deficiency. Genetic studies revealed 3 affected family members harbor a novel mutation of PTCH1 (c.838G> T; p.Glu280*). This unreported nonsense deleterious mutation results in either a putative truncated Ptch1 protein or in an absence of translated Ptch1 protein related to nonsense mediated messenger RNA decay. This heterozygous mutation cosegregates in the pedigree with GGS and CA with OBs aplasia/hypoplasia and with CHH in the proband suggesting a genetic linkage and an autosomal dominant mode of inheritance. No pathogenic rare variants in other KS/CHH genes cosegregated with these phenotypes. In additional 124 KS/CHH patients, 3 additional heterozygous, rare missense variants were found and predicted in silico to be damaging: p.Ser1203Arg, p.Arg1192Ser, and p.Ile108Met. CONCLUSION: This family suggests that the 2 main signs of KS can be included in GGS associated with PTCH1 mutations. Our data combined with mice models suggest that PTCH1 could be a novel candidate gene for KS/CHH and reinforce the role of the Hedgehog signaling pathway in pathophysiology of KS and GnRH neuron migration.

Decision coaching for people making healthcare decisions.

BACKGROUND: Decision coaching is non-directive support delivered by a healthcare provider to help patients prepare to actively participate in making a health decision. 'Healthcare providers' are considered to be all people who are engaged in actions whose primary intent is to protect and improve health (e.g. nurses, doctors, pharmacists, social workers, health support workers such as peer health workers). Little is known about the effectiveness of decision coaching. OBJECTIVES: To determine the effects of decision coaching (I) for people facing healthcare decisions for themselves or a family member (P) compared to (C) usual care or evidence-based intervention only, on outcomes (O) related to preparation for decision making, decisional needs and potential adverse effects. SEARCH METHODS: We searched the Cochrane Library (Wiley), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), CINAHL (Ebsco), Nursing and Allied Health Source (ProQuest), and Web of Science from database inception to June 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where the intervention was provided to adults or children preparing to make a treatment or screening healthcare decision for themselves or a family member. Decision coaching was defined as: a) delivered individually by a healthcare provider who is trained or using a protocol; and b) providing non-directive support and preparing an adult or child to participate in a healthcare decision. Comparisons included usual care or an alternate intervention. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Two authors independently screened citations, assessed risk of bias, and extracted data on characteristics of the intervention(s) and outcomes. Any disagreements were resolved by discussion to reach consensus. We used the standardised mean difference (SMD) with 95% confidence intervals (CI) as the measures of treatment effect and, where possible, synthesised results using a random-effects model. If more than one study measured the same outcome using different tools, we used a random-effects model to calculate the standardised mean difference (SMD) and 95% CI. We presented outcomes in summary of findings tables and applied GRADE methods to rate the certainty of the evidence. MAIN RESULTS: Out of 12,984 citations screened, we included 28 studies of decision coaching interventions alone or in combination with evidence-based information, involving 5509 adult participants (aged 18 to 85 years; 64% female, 52% white, 33% African-American/Black; 68% post-secondary education). The studies evaluated decision coaching used for a range of healthcare decisions (e.g. treatment decisions for cancer, menopause, mental illness, advancing kidney disease; screening decisions for cancer, genetic testing). Four of the 28 studies included three comparator arms.  For decision coaching compared with usual care (n = 4 studies), we are uncertain if decision coaching compared with usual care improves any outcomes (i.e. preparation for decision making, decision self-confidence, knowledge, decision regret, anxiety) as the certainty of the evidence was very low.  For decision coaching compared with evidence-based information only (n = 4 studies), there is low certainty-evidence that participants exposed to decision coaching may have little or no change in knowledge (SMD -0.23, 95% CI: -0.50 to 0.04; 3 studies, 406 participants). There is low certainty-evidence that participants exposed to decision coaching may have little or no change in anxiety, compared with evidence-based information. We are uncertain if decision coaching compared with evidence-based information improves other outcomes (i.e. decision self-confidence, feeling uninformed) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with usual care (n = 17 studies), there is low certainty-evidence that participants may have improved knowledge (SMD 9.3, 95% CI: 6.6 to 12.1; 5 studies, 1073 participants). We are uncertain if decision coaching plus evidence-based information compared with usual care improves other outcomes (i.e. preparation for decision making, decision self-confidence, feeling uninformed, unclear values, feeling unsupported, decision regret, anxiety) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with evidence-based information only (n = 7 studies), we are uncertain if decision coaching plus evidence-based information compared with evidence-based information only improves any outcomes (i.e. feeling uninformed, unclear values, feeling unsupported, knowledge, anxiety) as the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: Decision coaching may improve participants' knowledge when used with evidence-based information. Our findings do not indicate any significant adverse effects (e.g. decision regret, anxiety) with the use of decision coaching. It is not possible to establish strong conclusions for other outcomes. It is unclear if decision coaching always needs to be paired with evidence-informed information. Further research is needed to establish the effectiveness of decision coaching for a broader range of outcomes.

Evaluating co-created patient-facing materials to increase understanding of genetic test results.

Patients often have difficulty understanding genetic test reports. Technical language and jargon can impede comprehension and limit patients using results to act on findings. One potential way to improve patient understanding of genetic test reports is to provide patient-facing materials. This study aimed to examine understandability and actionability of co-created patient-facing materials for genetic test results in a research context. We combined interprofessional perspectives and patient engagement to co-create patient-facing materials for patients undergoing research genetic testing for congenital hypogonadotropic hypogonadism (Kallmann syndrome). The iterative development process was guided by principles of health literacy and human-centered design (i.e., design thinking). Readability was assessed using eight validated algorithms. Patients and parents evaluated materials using a web-based survey. The gold standard Patient Education Materials Assessment Tool for print materials (PEMAT-P) was employed to measure understandability (content, style, use of numbers, organization, design, use of visual aids) and actionability. PEMAT-P scores >80% were considered high quality. Results were analyzed descriptively and correlations performed to identify relationships between education/health literacy and PEMAT-P ratings. A consensus score of eight algorithms indicated the materials were an 8th -9th grade reading level. Our findings are consistent with the U.S. Department of Health and Human Services 'average difficulty' classification (i.e., 7th-9th grade). In total, 61 patients/parents evaluated the materials. 'Visual Aids' received the lowest mean PEMAT-P rating (89%). All other parameters scored 90%-97%. PEMAT-P scores did not differ according to educational attainment (less than college vs. college or more, p = 0.28). Participants with adequate health literacy were more likely to approve of the 'organization' of information (p < 0.05). Respondents with low health literacy had more favorable views of 'visual aids' (p < 0.01). Involving patients in a co-creation process can produce high-quality patient-facing materials that are easier to understand.

DCC/NTN1 complex mutations in patients with congenital hypogonadotropic hypogonadism impair GnRH neuron development.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia [Kallmann syndrome (KS)]. The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH. We performed whole-exome sequencing in a cohort of 133 CHH probands to test this hypothesis, and identified rare sequence variants (RSVs) in genes encoding for the FN3-domain encoding protein deleted in colorectal cancer (DCC) and its ligand Netrin-1 (NTN1). In vitro studies of these RSVs revealed altered intracellular signaling associated with defects in cell morphology, and confirmed five heterozygous DCC mutations in 6 probands-5 of which presented as KS. Two KS probands carry heterozygous mutations in both DCC and NTN1 consistent with oligogenic inheritance. Further, we show that Netrin-1 promotes migration in immortalized GnRH neurons (GN11 cells). This study implicates DCC and NTN1 mutations in the pathophysiology of CHH consistent with the role of these two genes in the ontogeny of GnRH neurons in mice.

GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty.

STUDY QUESTION: Are GnRH tests and serum inhibin B levels sufficiently discriminating to distinguish transient constitutional delay of growth and puberty (CDGP) from congenital hypogonadotropic hypogonadism (CHH) that affects reproductive health for life? SUMMARY ANSWER: Both parameters lack the specificity to discriminate CDGP from CHH. WHAT IS KNOWN ALREADY: GnRH tests and inhibin B levels have been proposed to differentiate CDGP from CHH. However, their diagnostic accuracies have been hampered by the small numbers of CHH included and enrichment of CHH patients with more severe forms. STUDY DESIGN, SIZE, DURATION: The aim of this study was to assess the diagnostic performance of GnRH tests and inhibin B measurements in a large cohort of CHH male patients with the whole reproductive spectrum. From 2008 to 2018, 232 males were assessed: 127 with CHH, 74 with CDGP and 31 healthy controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were enrolled in two French academic referral centres. The following measurements were taken: testicular volume (TV), serum testosterone, inhibin B, LH and FSH, both at baseline and following the GnRH test. MAIN RESULTS AND THE ROLE OF CHANCE: Among CHH patients, the LH response to the GnRH test was very variable and correlated with TV. Among CDGP patients, the LH peak was also variable and 47% of CHH patients had peak LH levels overlapping with the CDGP group. However, no patients with CDGP had an LH peak below 4.0 IU/l, while 53% CHH patients had LH peak below this threshold. Among CHH patients, inhibin B levels were also variable and correlated with TV and peak LH. Inhibin B was significantly lower in CHH patients than in CDGP patients but 50% of CHH values overlapped with CDGP values. Interestingly, all patients with CDGP had inhibin B levels above 35 pg/ml but 50% of CHH patients also had levels above this threshold. LIMITATIONS, REASONS FOR CAUTION: As CHH is very rare, an international study would be necessary to recruit a larger CHH cohort and consolidate the conclusion reached here. WIDER IMPLICATIONS OF THE FINDINGS: Peak LH and basal inhibin B levels are variable in both CHH and CDGP with significant overlap. Both parameters lack specificity and sensitivity to efficiently discriminate CHH from CDGP. This reflects the varying degree of gonadotropin deficiency inherent to CHH. These two diagnostic procedures may misdiagnose partial forms of isolated (non-syndromic) CHH, allowing them to be erroneously considered as CDGP. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Agence Française de Lutte contre le Dopage: Grant Hypoproteo AFLD-10 (to J.Y.); Agence Nationale de la Recherche (ANR): Grant ANR-09-GENO-017-01 (to J.Y.); European Cooperation in Science and Technology, COST Action BM1105; Programme Hospitalier de Recherche Clinique (PHRC), French Ministry of Health: PHRC-2009 HYPO-PROTEO (to J.Y.); and Programme Hospitalier de Recherche Clinique (PHRC) "Variété", French Ministry of Health, N° P081216/IDRCB 2009-A00892-55 (to P.C.). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Parent of origin differences in psychosocial burden and approach to BRCA risk management.

We conducted a mixed-method study to examine coping response in BRCA+ women based on parent of origin (maternally vs paternally inherited BRCA mutation). Quantitative findings (n = 408) revealed paternally inherited cases had genetic testing later and were more likely to have a cancer diagnosis. Having a maternally inherited mutation was the strongest predictor of proactive risk management response. Qualitative interviews (n = 56) identified proactive responses among maternally inherited cases compared to reactive responses in paternally inherited cases. Findings underscore the importance of unbiased pedigree analysis to determine cancer risk. Women with paternally inherited BRCA mutations may benefit from additional psychosocial support.

Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females.

OBJECTIVE: Research findings on the relationship between serum androgens and adipose tissue in older females are inconsistent. We aimed to clarify the relationship using state-of-the-art techniques to evaluate associations between body fat distribution and plasma testosterone (T) levels in older postmenopausal women. DESIGN: Observational, cross-sectional study of healthy, community dwelling postmenopausal women. PATIENTS AND MEASUREMENTS: Postmenopausal women (60-80 years old) were included in this study. Overall body composition was evaluated by dual-energy X-ray absorptiometry. Abdominal and thigh fat depots were measured by magnetic resonance imaging. Circulating T concentrations were analysed by liquid chromatography-tandem mass spectrometry. RESULTS: Thirty-five women (66.6 ± 0.8 years) participated in this study. T levels were positively associated with clinical proxy measures of adiposity including weight (ρ = 0.39), BMI (ρ = 0.43) and waist circumference (ρ = 0.39) (all P < 0.05). Fat mass and % body fat were correlated with T levels (ρ = 0.42 and 0.38 respectively, both P < 0.05). T correlated with overall and superficial abdominal fat (ρ = 0.34 and 0.37 respectively, both P < 0.05) but not with visceral adipose tissue. T increased with greater thigh fat (ρ = 0.49, P < 0.05) in both superficial and deep depots (ρ = 0.50 and 0.35 respectively, both P < 0.05). CONCLUSION: Our results suggest that postmenopausal women with higher circulating T levels have both higher regional and overall body adiposity. These findings underscore the sexual dimorphism in the relationship between serum androgen levels and adiposity.

Developing a rare disease chronic care model: Management of systemic sclerosis (MANOSS) study protocol.

AIM: The aim of the management of systemic sclerosis (MANOSS) study described in this protocol is to develop a chronic care model, based on a contextual analysis and stakeholder involvement, for patients living with the rare disease systemic sclerosis (SSc) in Switzerland. DESIGN: Applying an implementation science approach, this study starts with an explanatory sequential mixed method study for contextual analysis, followed by broad stakeholder involvement for model development and a Delphi study to reach consensus. METHODS: First, a quantitative cross-sectional survey with patients and healthcare professionals (HPs) will be conducted to identify current practice patterns of chronic illness management and technology readiness. Second, qualitative interviews with patients, family members and HPs will be performed to gain a deeper understanding of care needs identified in the quantitative survey. Third, a model of care will be co-created with input from patients, HPs and other experts. The eHealth enhanced Chronic Care Model will serve as a guiding framework. The new model and corresponding outcome parameters will be refined using a Delphi-study approach to reach consensus on a testable model of care for persons living with SSc. The protocol has received research ethics committee approval in September 2018 by the Swiss Ethics Committee. DISCUSSION: The MANOSS study's participatory approach is essential for contextual fit of the model for patients with SSc in this setting. Subsequent feasibility testing and implementation are planned to evaluate the model's value in relation to health disparities faced by this patient population. IMPACT: Patients living with this rare disease lack access to coordinated, specialized care and self-management support from qualified HPs. Reengineering of current care, with consideration for technological opportunities, is warranted to meet patients' and families' needs.

Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated. RESULTS: Of the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01). CONCLUSION: Pathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.

Fertility induction in hypogonadotropic hypogonadal men.

Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH is one of the few treatable forms of male infertility. Sperm induction protocols using gonadotrophins aim to replicate the natural endocrine control of spermatogenesis. Previously virilised men with adult-onset HH and normal testicular volume respond well to monotherapy in which human chorionic gonadotrophin (hCG) acts as a long-acting LH-analogue stimulating spermatogenesis. However, this approach is rarely successful for men with congenital HH (CHH) (eg, Kallmann syndrome), for whom combined gonadotrophin therapy (hCG + follicle-stimulating hormone [FSH]) is an absolute requirement to maximise fertility potential. Key baseline predictors of successful spermatogenesis-induction include prior spontaneous testicular development (ie, testicular volume [TV] > 4 mL), serum inhibin B (IB ) concentration >60 pg/mL and no history of maldescended testes (cryptorchidism).

Accuracy, satisfaction and usability of a flash glucose monitoring system among children and adolescents with type 1 diabetes attending a summer camp.

BACKGROUND: The study aimed to assess accuracy, satisfaction and usability of a flash glucose monitoring system (FGM) in children and adolescents with type 1 diabetes mellitus (T1DM) attending a diabetes summer camp. METHODS: Sixty-six children and adolescents with T1DM aged 6 to 17 years participating in a 7-day medically supervised summer camp were enrolled. Capillary blood glucose (BG) and flash glucose (FG) values were measured simultaneously at breakfast, lunch, and dinner and for any given FG value <72 mg/dL (<4.0 mmol/L) during daytime, <108 mg/dL (<6.0 mmol/L) at nighttime, >270 mg/dL (>15.0 mmol/L) or when patient symptoms were discordant with sensor readings. Sensor-related issues were documented and patients' and healthcare professionals' (HCPs) satisfaction was evaluated. RESULTS: FGM demonstrated satisfactory clinical accuracy compared to reference capillary BG values with 98.8% of values falling within the clinically acceptable zones (A and B) of the consensus error grid. Overall mean absolute relative difference (MARD) was 16.7% ± 16.1%. Specific calculations of mean absolute difference (MAD), mean relative difference (MRD), and mean difference (MD) demonstrated that FGM overestimated BG values across all glycemic ranges. Overall satisfaction with the FGM was high in 91.7% participants and 95.0% HCPs, although confidence in the system was low in 18.0% participants and 40.0% HCPs. CONCLUSIONS: The FGM exhibited satisfactory clinical accuracy. However, based on the present data, we conclude that no decision should be taken on the basis of a single, non-verified, FGM value alone. Our study highlights the need for revised therapeutic education for patients/families and further investigation on the integration of sensor readings in clinical decision-making.

Acceptance of the Advanced Practice Nurse in Lung Cancer Role by Healthcare Professionals and Patients: A Qualitative Exploration.

PURPOSE: The purpose of this study was to explore the acceptance of a novel role, the advanced practice nurse in lung cancer (APNLC), from the perspective of patients and healthcare professionals in a country lacking a regulatory oversight for advanced practice nursing (APN) roles. METHODS AND DESIGN: This study utilized a qualitative methodology using focus groups and semistructured interviews. Participants were purposively sampled in a Swiss academic medical center. Two focus groups were conducted: the first included nurses (n = 5) and the social worker, while the second targeted physicians (n = 6). The APNLC and patients (n = 4) were interviewed using semistructured interviews. Data were analyzed using thematic content analysis. FINDINGS: Three main themes were identified: APNLC role identification, APNLC role-specific contributions, and APNLC flexible service. Physicians and patients clearly recognized the APNLC role, noting contributions to continuity of care, psychosocial support, and enabling symptom self-management. Nurses perceived the APNLC role as overlapping with the oncology nurse role. Flexibility in providing care was seen as the strength of the APNLC role, yet this also posed organizational challenges. CONCLUSIONS: The new role appears to be well accepted by patients and physicians, yet barriers posed by nursing colleagues remain challenging. CLINICAL RELEVANCE: Based on existing literature and the present findings, we propose a model to guide future implementation and enhance acceptance of the APNLC role. This model comprises three actions: (a) formalizing nursing role expectations, (b) providing appropriate support and resources, and (c) promoting a national plan for APN regulation.

Patient Perspectives on Nurse-led Consultations Within a Pilot Structured Transition Program for Young Adults Moving From an Academic Tertiary Setting to Community-based Type 1 Diabetes Care.

PURPOSE: We aimed to evaluate patient self-management activities, patient perceptions of the therapeutic relationship and satisfaction with nurse-led consultations as part of a structured, pilot program transitioning young adults with type 1 diabetes (T1DM) to adult-oriented community-based practices. DESIGN AND METHODS: A descriptive, cross-sectional study of patients receiving nurse-led consultations. Patients provided sociodemographic/health information, glycated hemoglobin (HbA1c) measures and completed questionnaires assessing self-management (Revised Self-Care Inventory) and the therapeutic relationship (Caring Nurse-Patient Interaction - short scale). HbA1c values were compared to guideline recommendations. RESULTS: Twenty patients participated. HbA1c was ≤7.5% in 3/14 (21%) and 5/14 (36%) exhibited poor glycemic control (≥9.5%). The greatest concordance for self-care was in relation to insulin therapy (4.5±0.5) while patients reported the lowest adherence to diet recommendations (2.9±0.8). Overall satisfaction with nurse-led consultations was high (4±0.5 out of 5). Patients considered diabetes knowledge and technical competence as very important and were most pleased with the humanistic aspects of nursing care. Respect for privacy was deemed the most important (and most frequently observed) nursing attitude/behavior during consultations. CONCLUSIONS: Young adults found the nurse-led consultations with therapeutic education to develop T1DM self-care skills are an important complement to medical management during transition. PRACTICE IMPLICATIONS: Patient autonomy and privacy should be respected during this developmental period. Nurses taking a humanistic approach towards accompanying and supporting the patient can enhance the therapeutic relationship during transition and promote continuity of care. Transition nurses can use technical competence and therapeutic education to empower patients for self-management.

Adherence to treatment in men with hypogonadotrophic hypogonadism.

OBJECTIVE: Men with congenital hypogonadotrophic hypogonadism (CHH) typically require lifelong hormonal therapy, and discontinuing treatment can have negative health consequences. Little is known about adherence to treatment or the psychosocial impact of CHH. DESIGN: A sequential, multiple methods approach was used. A quantitative online survey assessed adherence to treatment, depressive symptoms and illness perceptions. Subsequently, qualitative focus groups explored patient-reported factors for adherence. PATIENTS: Adult men with CHH on at least 1 year of treatment were recruited internationally. MEASUREMENTS: Adherence (Morisky medication adherence scale), depressive symptoms (Zung self-rating depression scale) and patient perception of CHH (revised illness perception questionnaire) were assessed in an online survey, and comparisons were made to reference groups. Patient focus group discussions were conducted and thematic analysis was employed to identify patient-reported factors for adherence. RESULTS: In total, 101 men on long-term treatment were included (mean age 37 ± 11 years). Forty three percent (43/101) exhibited low medication adherence and a significantly elevated prevalence of mild, moderate or severe depressive symptoms (27%, 17%, 20%, respectively, all P < 0·001 vs reference population). Patients reported negative illness perceptions and significant psychosocial consequences. Focus group discussions (n = 3, 26 total patients) identified patient-, health professional- and healthcare system-related barriers as targets for improving adherence. CONCLUSIONS: Congenital hypogonadotrophic hypogonadism men are challenged to adhere to long-term treatment. Poor adherence may contribute to adverse effects on bone, sexual and psychological health. The psychosocial morbidity of CHH is significant and appears to be underappreciated by healthcare providers.