Cushing Syndrome in Childhood.

We describe a 15-year-old boy who presented with low back pain due to vertebral compression fractures, growth deceleration, excessive weight gain, rounded facies, dorsocervical fat pad, and hypertension. He was diagnosed as having Cushing syndrome (CS) due to primary pigmented nodular adrenocortical disease resulting in excess cortisol produced by the adrenal glands, leading to disruption of the hypothalamic-pituitary-adrenal axis. The most common cause of CS is exogenous glucocorticoids, with endogenous causes being extremely rare, often leading to delay in diagnosis or misdiagnosis. Herein, we review clinical presentation, screening for hypercortisolism, and decision-making in the diagnosis of CS, as well as therapeutic approaches. The wide range of clinical presentations in pediatric CS and the rarity of the condition can lead to difficulty in the recognition, diagnosis, and subsequent management of these patients. CS can be difficult to differentiate from more common exogenous obesity, and outpatient screening of cortisol excess is challenging. Early recognition and treatment of CS is necessary to avoid multisystemic complications, and patients with suspected endogenous CS should be referred to a tertiary care center with experienced pediatric endocrinology and surgery specialists. Further confirmatory diagnostic tests are necessary to distinguish corticotropin-independent from corticotropin-dependent forms of CS, including a high-dose dexamethasone suppression test, a corticotropin-releasing hormone stimulation test, and imaging. There can be challenges to the evaluation of CS, including complex inpatient testing and difficulty with localization on imaging. Long-term sequelae of CS, including adrenal insufficiency, obesity, hypertension, and mental health disorders, may remain despite definitive surgical treatment, meriting close follow-up with the primary care clinician and subspecialists.

Usage of electronic health record (eHR) viewer among healthcare professionals (HCProfs): A territory-wide study of 3972 participants.

BACKGROUND: The Electronic Health Record Sharing System (eHRSS) is an electronic platform for two-way communication between the public and private sectors in Hong Kong. The authorised healthcare professionals (HCProfs) could access and upload patients' health records on the eHR Viewer in the eHRSS. This study aims to evaluate the usage of eHR viewer among the HCProfs from the private sector by 1) examining the correlation of various factors and the data access of eHR viewer; 2) investigating the trend on data access and upload to eHR viewer by time period and domain. METHODS: A total of 3972 HCProfs from private hospitals, group practice, and solo practice were included in the study. Regression analysis was performed to identify the correlation between various factors and the data access to eHR viewer. Trends on accessing and data uploading to eHR viewer by time period and domains were evaluated. Trends on data uploading to eHR viewer by time period and domains were presented in the line chart as well. FINDINGS: All types of HCProfs had a higher likelihood of accessing the eHR viewer as compared to those from private hospitals. HCProfs with specialities (apart from anaesthesia) had a higher possibility of accessing the eHR viewer than general practitioners without specialities. HCProfs participating in the Public-Private Partnership (PPP) Programme and the eHealth System (Subsidies) (eHS(S)) were more likely to access the eHR viewer. The overall trend of accessing eHR viewer was rising notably from 2016 to 2022, every domain showed rising trends, especially the laboratory domain with a 5-times increase between 2016 and 2022. CONCLUSION: HCProfs with speciality were more likely to access the eHR viewer (except anaesthesiology), compared with the general practitioners. Participation in the PPP programmes and eHS(S) also increased the access rate of the eHR viewer. Besides, the use of eHR viewer (accessing and data uploading) would be influenced by social policy and the epidemic. Future research should focus on the impact of government programmes on eHRSS adoption.

Associations between adoption of eHealth management module and optimal control of HbA1c in diabetes patients.

In January 2021, the eHealth App was launched in Hong Kong by the Hong Kong government to support the Electronic Health Record Sharing System (eHRSS). A Health Management Module in the eHealth App introduced new functions to record blood pressure, blood sugar, and heart rate, and downloading and sharing records. This study aims to compare the level of glycaemic control between users of the eHealth App and non-users. Type 2 diabetes patients who have joined the eHRSS with existing haemoglobin A1c (HbA1c) level records are recruited. Correlations between predictors and optimal HbA1c control (<7%) are examined using logistic regression analyses. A total of 109,823 participants are included, with 76,356 non-users of eHealth App, 31,723 users of eHealth App, and 1744 users of the eHealth Management Module together with the App. We collect HbA1c values from Jan 2021 to May 2022, and they are 6 months after the use of the App on average. Users of the eHealth Management Module are found to have more optimal HbA1c levels across all subgroups, with the strongest effect observed in younger females (aOR = 1.66, 95% CI = 1.27-2.17). eHealth App usage is also positively associated with optimal HbA1c levels, particularly amongst younger females (aOR = 1.17, 95% CI = 1.08-1.26). Overall, users of eHealth App and eHealth Management Module demonstrate more optimal HbA1c levels when compared with non-users, particularly among younger adults and females. These findings support its potential adoption in diabetes patients. Future studies should examine the impact of eHealth interventions on other clinical targets and diabetes complications.

Factors Associated With the Acceptance of an eHealth App for Electronic Health Record Sharing System: Population-Based Study.

BACKGROUND: In the second stage of the Electronic Health Record Sharing System (eHRSS) development, a mobile app (eHealth app) was launched to further enhance collaborative care among the public sector, the private sector, the community, and the caregivers. OBJECTIVE: This study aims to investigate the factors associated with the downloading and utilization of the app, as well as the awareness, perception, and future improvement of the app. METHODS: We collected 2110 surveys; respondents were stratified into 3 groups according to their status of enrollment in the eHRSS. The primary outcome measure was the downloading and acceptance of the eHealth app. We collected the data on social economics factors, variables of the Technology Acceptance Model and Theory of Planned Behavior. Any factors identified as significant in the univariate analysis (P<.20) will be included in a subsequent multivariable regression analysis model. All P values ≤.05 will be considered statistically significant in multiple logistic regression analysis. The structural equation modeling was performed to identify interactions among the variables. RESULTS: The respondents had an overall high satisfaction rate and a positive attitude toward continuing to adopt and recommend the app. However, the satisfaction rate among respondents who have downloaded but not adopted the app was relatively lower, and few of them perceived that the downloading and acceptance processes are difficult. A high proportion of current users expressed a positive attitude about continuing to adopt and recommend the app to friends, colleagues, and family members. The behavioral intention strongly predicted the acceptance of the eHealth app (ß=.89; P<.001). Attitude (ß=.30; P<.001) and perceived norm; ß=.37; P<.001) played important roles in determining behavioral intention, which could predict the downloading and acceptance of the eHealth app (ß=.14; P<.001). CONCLUSIONS: Despite the high satisfaction rate among the respondents, privacy concerns and perceived difficulties in adopting the app were the major challenges of promoting eHealth. Further promotion could be made through doctors and publicity. For future improvement, comprehensive health records and tailored health information should be included.

An Analysis of Saturated Conditions in Hydrogen Peroxide Decontamination Applications.

This article discusses theoretical aspects of saturated vapor-liquid equilibrium for a hydrogen peroxide-water system at temperatures between 16°C and 30°C and humidities between 20% relative humidity to 65% relative humidity, common in pharmaceutical isolator decontamination applications. A discrepancy is pointed out between two competing sets of empirical relations published in the literature that are used to calculate saturated parameters. It is shown how the two published sets can result in four combinations of equations. The four sets of equations were compared to existing published data as well as new data from experiments conducted in this study, and it is shown that one set of relations consistently provided the best match to the experimental data. This set came from a hybrid combination of the previously published equations. This has practical implications for hydrogen peroxide sensors that rely on saturated theory for calibration. In addition, new empirical relations aimed at simplifying the calculation of relevant parameters such as hydrogen peroxide concentration, mole fraction of hydrogen peroxide in the condensed liquid, and relative humidity are presented. The concept of relative saturation is discussed and a new procedure for calculating this parameter during a decontamination cycle is presented, incorporating the results from our experiments. Together the updated theoretical framework and simplified empirical relationships can be used to estimate in a simple, direct, and accurate manner where a decontamination cycle is operating in relation to the 100% saturation level, at which point condensation is likely to form in the isolator. This provides a repeatable and objective measure, useful for monitoring and comparing decontamination cycles.

The Perceptions of and Factors Associated With the Adoption of the Electronic Health Record Sharing System Among Patients and Physicians: Cross-Sectional Survey.

BACKGROUND: The electronic health record sharing system (eHRSS) was implemented as a new health care delivery platform to facilitate two-way communication between the public and private sectors in Hong Kong. OBJECTIVE: This study aimed to investigate the perceptions of and factors associated with the adoption of eHRSS among patients, the general public, and private physicians. METHODS: Telephone interviews were conducted in 2018 by using a simple random sampling strategy from a list of patients who had enrolled in the eHRSS and a territory-wide telephone directory for nonenrolled residents. We completed 2000 surveys (1000 each for enrolled and nonenrolled individuals). Private physicians completed self-administered questionnaires, including 762 valid questionnaires from 454 enrolled physicians and 308 nonenrolled physicians. RESULTS: Most participants (707/1000, 70.70%) were satisfied with the overall performance of the eHRSS. Regarding registration status, most nonenrolled patients (647/1000, 64.70%) reported that "no recommendation from their physicians and family members" was the major barrier, whereas more than half of the physicians (536/1000, 53.60%) expressed concerns on "additional workload due to use of eHRSS." A multivariate regression analysis showed that patients were more likely to register when they reported "other service providers could view the medical records" (adjusted odds ratio [aOR] 6.09, 95% CI 4.87-7.63; P<.001) and "friends' or family's recommendation or assistance in registration" (aOR 3.51, 95% CI 2.04-6.03; P=.001). Physicians were more likely to register when they believed that the eHRSS could improve the quality of health care service (aOR 4.70, 95% CI 1.77-12.51; P=.002) and were aware that the eHRSS could reduce duplicated tests and treatments (aOR 4.16, 95% CI 1.73-9.97; P=.001). CONCLUSIONS: Increasing the possibility of viewing patients' personal medical record, expanding the sharable data scope for patients, and highlighting the benefits of the system for physicians could be effective to enhance the adoption of the eHRSS.

Adoption of an Electronic Patient Record Sharing Pilot Project: Cross-Sectional Survey.

BACKGROUND: The Public Private Interface-Electronic Patient Record (PPI-ePR) system was implemented as a new electronic platform to facilitate collaboration between the public and private sectors in Hong Kong. However, its barriers to participate and benefits have not been comprehensively assessed. OBJECTIVE: This study aimed to evaluate the awareness, acceptance, perceived benefits, and obstacles to participation among private doctors and the general public. METHODS: From December 2012 to January 2013, 2435 telephone interviews were performed by trained interviewers to survey randomly selected patients who were enrolled or not enrolled in the PPI-ePR system. In addition, self-administered surveys were sent by postal mail to 4229 registered doctors in Hong Kong. The questionnaires for both patients and doctors contained questions on subjects' awareness, acceptance, and perceptions of the PPI-ePR, perceived benefits and obstacles of participating in the program, reasons for not using the system after enrolling, and perceived areas for service improvement of the system. RESULTS: More than 53.1% (266/501) of enrolled patients believed that the PPI-ePR system would improve health care quality by reducing duplicate tests and treatments, while more than 76.8% (314/409) of enrolled doctors emphasized timely access to patients' medical records as the biggest benefit of their enrollment. Among nonenrolled patients, unawareness of the project was the most popular obstacle to enrolling in the PPI-ePR system (483/1200, 40.3%). Regarding nonenrolled doctors, the complicated registration process hindered them from participating in the program the most (95/198, 48.0%). Television, newspaper, and magazine advertisements and medical profession newsletters or journals were suggested as the most effective means to encourage participation in the program among surveyed patients (1297/1701, 76.2%) and doctors (428/610, 70.2%), respectively. Lack of clinical indication requiring data extraction from other hospitals was the main reason for low level of PPI-ePR use. CONCLUSIONS: This study comprehensively assessed the popularity, perceived benefits, and hindering factors of enrolling in the PPI-ePR system in Hong Kong. Low levels of awareness, few privacy concerns, and inactive use of the PPI-ePR system were among the key features for patients and physicians. Public promotions, simplified logistics, and a user-friendly online interface were suggested to improve the coverage and effectiveness of health information exchange between private and public health care sectors.

Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Long-term follow-up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation-avoiding regimens.

BACKGROUND: The adverse effects of irradiation on endocrine function among patients with pediatric brain tumor are well documented. Intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) without central nervous system (CNS) irradiation has demonstrated efficacy in a proportion of very young children with some malignant CNS tumors. This study assessed the long-term endocrine function of young children following chemotherapy-only treatment regimens. PROCEDURES: A retrospective chart review was performed on 99 patients under 6 years of age with malignant brain tumors newly diagnosed between May 1991 and October 2010 treated with irradiation-avoiding strategies. Thirty patients survived post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0-22.25 years). The patient cohort included 18 males and 12 females (mean age at AuHCR of 2.5 years, range 0.8-5.1 years). RESULTS: All 30 surviving patients had documented normal age-related thyroid function, insulin-like growth factor binding protein 3 (IGF-BP3), prolactin, testosterone, and estradiol levels. Insulin-like growth factor 1 age-related levels were abnormal in one child with normal height. Ninety-seven percent of patients had normal cortisol levels, while follicle-stimulating hormone and LH levels among females were normal in 83% and 92%, respectively, and in 100% of males. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% of patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. CONCLUSIONS: These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation.

The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: A cohort study.

BACKGROUND: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. METHODS: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for ≥2years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. RESULTS: A total of 20,252 eligible patients with an average age of 64.5years (standard deviation 15.0) were included. The admission rate at 24months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR]=1.25, 95% CI 1.08 to 1.43, p=0.002 at 12months; AHR=1.17, 95% CI 1.04 to 1.31, p=0.009 at 24months) and all causes (AHR=1.12, 95% CI 1.05 to 1.19, p<0.001 at 24months) than perindopril users. CONCLUSIONS: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended.

Sex-dependent changes in metabolism and behavior, as well as reduced anxiety after eliminating ventromedial hypothalamus excitatory output.

OBJECTIVES: The ventromedial hypothalamic nucleus (VMH) regulates energy homeostasis as well as social and emotional behaviors. Nearly all VMH neurons, including those in the sexually dimorphic ventrolateral VMH (VMHvl) subregion, release the excitatory neurotransmitter glutamate and use the vesicular glutamate transporter 2 (Vglut2). Here, we asked how glutamatergic signaling contributes to the collective metabolic and behavioral responses attributed to the VMH and VMHvl. METHODS: Using Sf1-Cre and a Vglut2 floxed allele, Vglut2 was knocked-out in SF-1 VMH neurons (Vglut2 (Sf1-Cre) ). Metabolic and neurobehavioral assays were carried out initially on Vglut2 (fl/fl) and Vglut2 (Sf1-Cre) mice in a mixed, and then in the C57BL/6 genetic background, which is prone to hyperglycemia and diet induced obesity (DIO). RESULTS: Several phenotypes observed in Vglut2 (Sf1-Cre) mice were largely unexpected based on prior studies that have perturbed VMH development or VMH glutamate signaling. In our hands, Vglut2 (Sf1-Cre) mice failed to exhibit the anticipated increase in body weight after high fat diet (HFD) or the impaired glucose homeostasis after fasting. Instead, there was a significant sex-dependent attenuation of DIO in Vglut2 (Sf1-Cre) females. Vglut2 (Sf1-Cre) males also display a sex-specific loss of conditioned-fear responses and aggression accompanied by more novelty-associated locomotion. Finally, unlike the higher anxiety noted in Sf1 (Nestin-Cre) mice that lack a fully formed VMH, both male and female Vglut2 (Sf1-Cre) mice were less anxious. CONCLUSIONS: Loss of VMH glutamatergic signaling sharply decreased DIO in females, attenuated aggression and learned fear in males, and was anxiolytic in males and females. Collectively, our findings demonstrate that while glutamatergic output from the VMH appears largely dispensable for counter regulatory responses to hypoglycemia, it drives sex-dependent differences in metabolism and social behaviors and is essential for adaptive responses to anxiety-provoking stimuli in both sexes.

The effectiveness of perindopril vs. lisinopril on reducing the incidence of diabetes and renal diseases: A cohort study of 20,252 patients.

BACKGROUND: Lisinopril and perindopril are two commonly used first-line antihypertensive agents. Few studies compared their effectiveness in reducing the incidence of renal diseases and diabetes. METHODS: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for at least 2 years. Patients prescribed the angiotensin converting enzyme inhibitors (ACEIs) for <1 month were excluded. The incidence of admissions due to renal diseases and diabetes was evaluated. We used Cox proportional hazard regression models to assess hospital admissions as the outcome measures, adjusting for age, sex, socioeconomic status, service types, and the proportion of days covered as a measure of medication adherence. The regression models were constructed with propensity score matching to minimize indication biases. RESULTS: 20,252 eligible patients with an average age of 64.5 years (SD 15.0) were included. The admission rates 24 months within the date of index prescription due to renal diseases were 3.1% (lisinopril) and 2.3% (perindopril); and 9.6% (lisinopril) and 7.2% (perindopril) for diabetes. Except for admissions due to diabetes at 6 months, lisinopril users were significantly more likely to be admitted due to renal diseases (adjusted hazard ratios: 1.304 to 1.378) and diabetes (1.146 to 1.231) than perindopril users at all time points. CONCLUSIONS: Patients prescribed different ACEIs might have a different incidence of hospital admissions. Future studies should be conducted to evaluate the comparative effectiveness of different ACEIs on various patient-centered outcomes by head-to-head randomized controlled trials.

Duration of initial antihypertensive prescription and medication adherence: a cohort study among 203,259 newly diagnosed hypertensive patients.

BACKGROUND: Optimal adherence with antihypertensive medications is crucial to prevent hypertension-related complications. This study evaluated whether the duration of initial antihypertensive prescription is associated with better medication adherence in a large sample of Chinese hypertensive patients. METHODS AND RESULTS: From a validated clinical database which consists of all patients in the public healthcare sector in Hong Kong, all patients on their first-ever antihypertensive agent from 2001 to 2005 (N=203,259) were included and followed-up for 12 months (and up to 5 years in separate analyses). The average age was 58.7 years (SD 17.3), and the overall rate of optimal adherence (as measured by having the Proportion of Days Covered≥0.80) was 32.4%. The proportion of patients whose initial prescriptions lasted for ≤6 days; 7-14 days; 15-28 days and ≥29 days was 23.7%, 24.3%, 15.1% and 37.0%, respectively. The corresponding proportion of optimal adherence was 18.1%, 20.1%, 31.0% and 50.3%. The binary logistic regression analysis showed that after controlling for age, sex, socioeconomic status, service type, drug class, and district of residence, those whose initial prescription was 7-14 days (adjusted odds ratio [AOR]=1.17, 95% C.I. 1.12-1.22); 15-28 days (AOR=1.90, 95% C.I. 1.82-1.99) and ≥29 days (AOR=4.13, 95% C.I. 3.96-4.31) were significantly more likely to be adherent than those who were prescribed for ≤6 days (all p<0.001). These findings remained significant in separate analyses where the period of follow-up was extended to 5 years. CONCLUSIONS: Shorter duration of first antihypertensive prescriptions was associated with poorer medication adherence, and this practice should be avoided if possible.

The incidence of cancer deaths among hypertensive patients in a large Chinese population: a cohort study.

Current evidence is mixed regarding the association between antihypertensive prescriptions and cancer mortality. We evaluated this association in a large Chinese hypertensive population. We followed for five years all patients who were prescribed their first-ever antihypertensive agents between 2001 and 2005 in a public healthcare sector of Hong Kong. The association between antihypertensive drug class and cancer mortality was evaluated by Cox proportional hazard models with propensity score matching. Age, gender, socioeconomic status, service settings, district of residence, proportion of days covered reflecting medication adherence, and the number of comorbidities were adjusted. From 217,910 eligible patients, 9500 (4.4%) died from cancer within five years after their first-ever antihypertensive prescription. Most cancer deaths occurred in the digestive (38.9%) and respiratory system (30.4%); the breast (6.2%); and the lympho-hematopoietic tissues (5.3%). The proportion of patients who died from cancer was the highest in the calcium channel blocker (CCB) group (6.5%), followed by thiazide diuretics (4.4%), angiotensin converting enzyme inhibitors (4.2%) and ß-blockers (2.6%). When compared with ß-blockers, patients prescribed CCBs (Adjusted Hazard Ratio [AHR]=1.406, 95% C.I. 1.334-1.482, p<0.001) were more likely to die from cancer. Thiazide users were also more likely to suffer from cancer deaths (AHR=1.364, 95% C.I. 1.255-1.483, p<0.001), but became insignificant in stratified analysis. The association between cancer mortality and use of CCB, and perhaps thaizide, may alert physicians to the need for more meticulous and comprehensive care of these patients in clinical practice. We recommend prospective studies to evaluate cause-and-effect relationships of these associations.

An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females.

Estrogen-receptor alpha (ERα) neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL) control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1(+) VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα(+) neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

Early and late endocrine effects in pediatric central nervous system diseases.

Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.

Factors associated with multimorbidity and its link with poor blood pressure control among 223,286 hypertensive patients.

Multimorbidity has become the norm worldwide as populations age. It remains, however, infrequently researched. This study evaluated factors associated with multimorbidity in a predominantly Chinese hypertensive population. We included all adult patients prescribed their first antihypertensive agents in the entire public sector in Hong Kong from a validated database. Multimorbidity was defined as having one or more medical conditions (cardiovascular diseases; respiratory diseases; diabetes or impaired fasting glucose; renal disease) in addition to hypertension. We studied the prevalence of multimorbidity and performed multinomial regression analyses to evaluate factors independently associated with multimorbidity. 223,286 hypertensive patients (average age of 59.9 years, SD 17.6) were included. The prevalence of having 0, 1 and ≥ 2 additional conditions was 59.6%, 32.8% and 7.5%, respectively. The most common conditions were cardiovascular disease (24.2%) and diabetes (23.0%), followed by respiratory disorders (14.6%) and renal disease (10.9%). Older age (>50 years), male sex, lower household income, receipt of social security allowance and suboptimal blood pressure control (>140 mmHg or >90 mmHg; >130 mmHg or >80 mmHg for diabetes patients; AOR = 3.38-4.49) were significantly associated with multimorbidity. There exists a synergistic effect among these variables as older (≥ 70 years), male patients receiving security allowance had substantially higher prevalence of multimorbidity (19.9% vs 7.5% among all patients). Multimorbidity is very common in hypertensive patients and its prevalence increased markedly with the presence of risk factors identified in this study. Hypertensive patients with multimorbidities should receive more meticulous clinical care as their blood pressure control tends to be poorer.