Luteinizing hormone beta mutation and hypogonadism in men and women

Selective luteinizing hormone deficiency due to mutations in the luteinizing hormone beta-subunit gene (LHB) is a rare cause of hypogonadism. We describe the clinical features of a consanguineous family in which three siblings, two men and one woman, had hypogonadism related to isolated luteinizing hormone deficiency. These subjects have a newly discovered homozygous mutation of a 5' splice site in LHB: IVS2+1G-->C. This mutation disrupts the splicing of messenger RNA (mRNA), generating a gross abnormality in the processing of the luteinizing hormone beta-subunit mRNA, which abrogates the secretion of luteinizing hormone. We also determined that the female phenotype of this LHB mutation is characterized by normal pubertal development, secondary amenorrhea, and infertility.     

Early markers of vulnerable language skill development in galactosaemia

There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative ‘red flag’ behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic development in two 18-month-old infants with GAL (one of each gender). Results identified the male as displaying significantly poorer pre-linguistic skills than both his matched peers and relative to the female infant with GAL, whose pre-linguistic skills were commensurate with or better than her matched peers. The results suggest that by 18 months of age, differential developmental language skills can be identified in infants with GAL when the focus is on pre-linguistic communication behaviours.     

An Intensive Intervention to Reduce Readmissions for Frequently Hospitalized Patients: the CHAMP Randomized Controlled Trial

BackgroundA small number of patients are disproportionally readmitted to hospitals. The Complex High Admission Management Program (CHAMP) was established as a multidisciplinary program to improve continuity of care and reduce readmissions for frequently hospitalized patients.ObjectiveTo compare hospital utilization metrics among patients enrolled in CHAMP and usual care.DesignPragmatic randomized controlled trial.ParticipantsInclusion criteria were as follows: 3 or more, 30-day inpatient readmissions in the previous year; or 2 inpatient readmissions plus either a referral or 3 observation admissions in previous 6 months.InterventionsPatients randomized to CHAMP were managed by an interdisciplinary team including social work, physicians, and pharmacists. The CHAMP team used comprehensive care planning and inpatient, outpatient, and community visits to address both medical and social needs. Control patients were randomized to usual care and contacted 18 months after initial identification if still eligible.Main MeasuresPrimary outcome was number of 30-day inpatient readmissions 180 days following enrollment. Secondary outcomes were number of hospital admissions, total hospital days, emergency department visits, and outpatient clinic visits 180 days after enrollment.Key ResultsThere were 75 patients enrolled in CHAMP, 76 in control. Groups were similar in demographic characteristics and baseline readmissions. At 180 days following enrollment, CHAMP patients had more inpatient 30-day readmissions [CHAMP incidence rate 1.3 (95% CI 0.9–1.8) vs. control 0.8 (95% CI 0.5–1.1), p=0.04], though both groups had fewer readmissions compared to 180 days prior to enrollment. We found no differences in secondary outcomes.ConclusionsFrequently hospitalized patients experienced reductions in utilization over time. Though most outcomes showed no difference, CHAMP was associated with higher readmissions compared to a control group, possibly due to consolidation of care at a single hospital. Future research should seek to identify subsets of patients with persistently high utilization for whom tailored interventions may be beneficial.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640KEY WORDS: care transitions, readmissions, care models, continuity of care, randomized controlled trial

A small number of patients account for a disproportionate number of hospital readmissions.¹ While medically diverse, many patients who are frequently hospitalized have behavioral or social needs that require holistic care models emphasizing more than medical care alone.² This population challenges a system of care that fragments hospital-based care and ambulatory care, creating systematic discontinuity for patients who may require longitudinal relationship-based care to meet their complex needs.³ In qualitative studies, patients who are frequently hospitalized report frustration with care fragmentation, causing them to perceive a lack of continuity and a loss of trust with the medical system.⁴Innovative care models have sought to reduce readmissions through redesigning care delivery, improving care coordination, and connecting patients to existing resources.^5–8 A systematic review of interventions for frequently hospitalized patients found a heterogeneous group of care models.⁹ Importantly, the majority of studies were observational. Many patients experience a reduction in utilization after an initial period of frequent admissions,¹⁰ limiting the ability of observational studies to measure a specific program’s effect due to the natural decline in readmissions over time. A randomized trial of a “healthcare hotspotting” intervention for patients in Camden, NJ, reported no change in hospitalization rates compared to a control group.¹¹ Though this intervention was an intensive interdisciplinary effort that enrolled patients while still hospitalized, it focused primarily on connecting patients to existing outpatient resources. Other intensive outpatient-only interventions have failed to reduce healthcare utilization.¹² Interventions that focus on improving care across clinical settings (i.e., both inside and outside of the hospital) may have a different effect.We created the Complex High Admission Management Program (CHAMP) as a quality improvement initiative to improve inpatient and outpatient care and reduce inpatient readmissions of patients frequently admitted to our hospital. The CHAMP multidisciplinary team works to foster longitudinal relationships with patients who suffer from systematic discontinuity. A pilot pre-post analysis of CHAMP observed reductions in readmission;¹³ however, results may have been confounded by the aforementioned tendency for utilization to decline over time.¹⁰ In this study, we conducted a randomized trial of CHAMP compared with usual care to accurately assess the program’s effect on hospital readmissions.