Introduction to the dietary management of obesity in adults.

Obesity is a multifaceted and complex condition that requires holistic management. It currently affects nearly one in four adults in the UK, with the UK ranked 10th globally for the highest obesity rates. Obesity is projected to have an economic burden of ∼£2 billion per year by 2030 in the UK.1 Excess weight gain can coincide with myriad health concerns and multiple health conditions, which can be physical, metabolic or psychosocial. This includes type 2 diabetes mellitus (T2DM), hypertension, coronary heart disease, osteoarthritis, obstructive sleep apnoea, reproductive disorders, depression and cancer2; hence, there has been a significant emphasis on obesity prevention. Obesity is often associated with weight stigma, impacting psychological wellbeing and quality of life. This can influence an individual's likelihood of seeking support, delaying appropriate input from healthcare professionals, with a knock-on effect on pre-existing health conditions. This review explores the management of obesity from a nutritional perspective, because modifying dietary intake is essential to reduce the risk of non-communicable diseases, including those associated with obesity.

Controlled-release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta-analysis.

Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This meta-analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well-tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out-of-office (including 24-h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random-effect meta-analyses. A risk of bias assessment was performed using the Cochrane risk-of-bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled-release melatonin (not an immediate-release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: -7.88 to .73; I2  = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well-tolerated. Due to the limited number of high-quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.

Choosing Wisely in Pediatric Hospital Medicine: 5 New Recommendations to Improve Value.

OBJECTIVES: The health care system faces ongoing challenges due to low-value care. Building on the first pediatric hospital medicine contribution to the American Board of Internal Medicine Foundation Choosing Wisely Campaign, a working group was convened to identify additional priorities for improving health care value for hospitalized children. METHODS: A study team composed of nominees from national pediatric medical professional societies was convened, including pediatric hospitalists with expertise in clinical care, hospital leadership, and research. The study team surveyed national pediatric hospitalist LISTSERVs for suggestions, condensed similar responses, and performed a literature search of articles published in the previous 10 years. Using a modified Delphi process, the team completed a series of structured ratings of feasibility and validity and facilitated group discussion. The sum of final mean validity and feasibility scores was used to identify the 5 highest priority recommendations. RESULTS: Two hundred seven respondents suggested 397 preliminary recommendations, yielding 74 unique recommendations that underwent evidence review and rating. The 5 highest-scoring recommendations had a focus on the following aspects of hospital care: (1) length of intravenous antibiotic therapy before transition to oral antibiotics, (2) length of stay for febrile infants evaluated for serious bacterial infection, (3) phototherapy for neonatal hyperbilirubinemia, (4) antibiotic therapy for community-acquired pneumonia, and (5) initiation of intravenous antibiotics in infants with maternal risk factors for sepsis. CONCLUSIONS: We propose that pediatric hospitalists can use this list to prioritize quality improvement and scholarly work focused on improving the value and quality of patient care for hospitalized children.

Pharmacologic Evidence of Green Tea in Targeting Tyrosine Kinases.

BACKGROUND: Green tea has been extensively studied for its potential health benefits against diseases, such as cancers, cognitive degenerative diseases, and cardiovascular diseases. METHODS: The authors undertook a structured search of peer-reviewed research articles from three databases including PubMed, Embase, and Ovid MEDLINE. Recent and up-to-date studies relevant to the topic were included. RESULTS: Green tea extract exerts its functions by interacting with multiple signalling pathways in human cells. Protein tyrosine kinase is one of the examples. Abnormal activation of tyrosine kinase is observed in some tumour cells. Green tea extract inhibits phosphorylation, reduces expression, or attenuates downstream signalling of epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor, and non-receptor tyrosine kinase. Combination of green tea extract with tyrosine kinase inhibitors may provide synergistic effects by overcoming acquired resistance. CONCLUSION: Green tea extract can affect multiple receptor targets. In the current review, we discuss the pharmacological mechanisms of green tea on tyrosine kinases and their implications on common diseases.

Fostering gerontology students' competence in Interprofessional collaborative practice.

BACKGROUND: Interprofessional collaborative practice (IPCP) is increasingly recognised as being crucial for the provision of holistic care and optimising health outcomes among older adults, many with multiple complex health problems. However, little is known about the challenges of facilitating this in practice. Therefore, this study explores these issues from the perspective of different healthcare professionals and how this might inform interprofessional education curricula. METHODS: Sixteen different healthcare professionals working in a variety of aged care (acute, rehabilitative and community) settings were invited to participate in individual semi-structured in-depth interviews designed to: (i) explore the meaning of IPCP; (ii) explore the facilitators of and barriers to IPCP; and (iii) examine the opportunities and challenges in interprofessional gerontological education. All interviews were tape-recorded and transcribed verbatim with thematic analysis conducted by two independent researchers. RESULTS: Three major themes emerged from the interviews: the need for IPCP; role preparedness, scope and liability; and strategies for interprofessional education. Respondents shared a common belief that IPCP improves the quality of life of older adults in both hospital and community settings by improving person-centred coordinated care and decision making in care planning. However, respondents perceived major barriers to IPCP to be lack of knowledge about healthcare professionals' scope of practice, lack of training in interprofessional collaboration, professional culture and stereotypes, and liability issues. Suggested approaches to overcome these barriers included innovative teaching and learning approaches, engaging students early on in the curriculum of health professional degree programmes, and enhancing collaborative effective communication in health and social care settings. CONCLUSIONS: It is anticipated that these findings will be used to inform the development of a new interprofessional gerontological education curriculum that aims to enhance students' competence in IPCP.

An overview of drug discovery efforts for eczema: why is this itch so difficult to scratch?

Introduction: Atopic dermatitis (AD) is a type of allergic/inflammatory dermatitis characterized by itch and an impairment in quality of life.Areas covered: Herein, the authors review drug discovery efforts for AD, highlighting the clinical efficacy of novel drugs, with a particular focus on the relief of pruritus. Topical agents include emollients, topical antihistamines, corticosteroids, calcineurin inhibitors and herbs. Recently, topical phosphodiesterase E4 (PDE4) inhibitors like crisaborole have become available and are efficacious for mild to moderate AD with few side effects. For more severe AD, monoclonal antibodies like dupilumab are considered as efficacious subcutaneous treatment options. In severe and recalcitrant AD, systemic treatment can ameliorate AD symptoms.Expert opinion: Many topical and systemic medications have demonstrated therapeutic benefits for AD. Indeed, randomized trials have shown that topical PDE4 inhibitors and subcutaneous dupilumab are safe and efficacious. Objective tools to evaluate itch and gauge treatment efficacy is important, but current methodology relies primarily on clinical scores. AD is a systemic atopic disease with a lot of complicated psychosocial issues. Suboptimal efficacy is often due to poor compliance and unrealistic expectation of curative treatment, rendering treatment difficult despite the existence of effective medications.

A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients.

BACKGROUND & AIMS: Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. METHODS: 279 MCI outpatients aged ≥65 years with serum homocysteine ≥10.0 µmol/L were randomly assigned to take either methylcobalamin 500 µg and folic acid 400 µg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. RESULTS: The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9 ± sd 3.5 µmol at baseline to 9.3 ± 2.4 µmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P = 0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P = 0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P = 0.005). CONCLUSIONS: Vitamin B12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. CLINICAL TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.

Effects of Acupuncture on the Recovery Outcomes of Stroke Survivors with Shoulder Pain: A Systematic Review.

BACKGROUND: Poststroke shoulder pain limits stroke survivors' physical functioning, impairs their ability to perform daily activities, and compromises their quality of life. The use of acupuncture to manage shoulder pain after a stroke is believed to free the blockage of energy flow and produce analgesic effects, but the evidence is unclear. We therefore conducted a systematic review to summarize the current evidence on the effects of acupuncture on the recovery outcomes of stroke survivors with shoulder pain. METHODS: Fourteen English and Chinese databases were searched for data from January 2009 to August 2017. The review included adult participants with a clinical diagnosis of ischemic or hemorrhagic stroke who had developed shoulder pain and had undergone conventional acupuncture, electroacupuncture, fire needle acupuncture, or warm needle acupuncture. The participants in the comparison group received the usual stroke care only. RESULTS: Twenty-nine randomized controlled trials were included. Most studies were assessed as having a substantial risk of bias. Moreover, due to the high heterogeneity of the acupuncture therapies examined, pooling the results in a meta-analysis was not appropriate. A narrative summary of the results is thus presented. The review showed that conventional acupuncture can be associated with benefits in reducing pain and edema and improving upper extremity function and physical function. The effects of conventional acupuncture on improving shoulder range of motion (ROM) are in doubt because this outcome was only examined in two trials. Electroacupuncture might be effective in reducing shoulder pain and improving upper extremity function, and conclusions on the effects of electroacupuncture on edema, shoulder ROM, and physical function cannot be drawn due to the limited number of eligible trials. The evidence to support the use of fire needle or warm needle acupuncture in stroke survivors with shoulder pain is also inconclusive due to the limited number of studies. CONCLUSION: Although most studies reviewed concluded that conventional and electroacupuncture could be effective for management of shoulder pain after stroke, the very high potential for bias should be considered. Further work in this area is needed that employs standardized acupuncture treatment modalities, endpoint assessments, and blinding of treatments.

Complementary, Alternative and Integrative Medicine for Childhood Atopic Dermatitis.

BACKGROUND: Atopic Dermatitis (AD) is a chronic relapsing dermatosis associated with itch, sleep disturbance and poor quality of life. Treatment of AD includes the use of emollients, and topical and systemic immunomodulating agents. Many patients also use complementary and alternative medicine (CAM). OBJECTIVE: This article reviews the pathophysiology of AD, clinical trials and recent patents involving various modalities of CAM in the treatment of AD. METHODS: A Medline/Pubmed search was conducted using Clinical Queries with the key terms "Chinese Medicine OR Complementary and Alternative medicine" AND "Eczema OR Atopic dermatitis". The search strategy included meta-analyses, Randomized Controlled Trials (RCTs), clinical trials, reviews and pertinent references. Patents were searched using the key term "atopic dermatitis" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. RESULTS: Only a few RCTs evaluated the efficacy of Chinese medicinal herbs in treating AD. There was some evidence for other modalities of CAM. Integrative Medicine (IM) usually refers to the various forms of CAM that combine conventional western medicine and Chinese medicine. Supporting evidence for the efficacy of IM in the treatment of AD is presently lacking. Integration is difficult. Western medicine practitioners are often ignorant about CAM and IM. Parents are concerned about the potential side effects of Western medicine and will tend to be non-compliant with the conventional Western component of IM. Recent patents on CAM and IM are reviewed. Most CAM patents are herbal compositions, evidence on their efficacy is generally lacking. CONCLUSION: AD is a complex disease. The psychodynamics of the child and his/her family is the reason for the often suboptimal outcomes. Both Western and CAM practitioners should collaborate to create a mutually encouraging environment for the advances of IM. CAM and IM publications and patents are reviewed. Evidence of their efficacy is generally lacking. Further research is needed.

Community pharmacists' perceptions about pharmaceutical service of over-the-counter traditional Chinese medicine: a survey study in Harbin of China.

BACKGROUND: This study aims to investigate community pharmacist's perception on the provision of over-the-counter (OTC) traditional Chinese medicine (TCM) pharmaceutical services; focusing on the areas of their attitude, general practice, perceived barriers and suggested improvements. METHODS: Questionnaire survey targeting community pharmacists in Harbin of China was applied in this study. Questionnaires were distributed and collected at community pharmacies. Data was analyzed by combining descriptive analysis and Chi-test. RESULTS: 280 valid questionnaires were collected, giving a response rate of 78%. Respondents generally showed positive attitude towards OTC TCM pharmaceutical services. However, they were uncertain about whether such pharmaceutical services should be considered as their primary responsibility. Respondents indicated that they acted proactively to find out all the medicines taken by their patients and to remind consumers of possible OTC TCM adverse reactions. However, they were less keen on recommending or re-directing consumers to suitable OTC TCM. The three main barriers hindering the provision of OTC TCM pharmaceutical service identified in this study were "insufficient professional knowledge" (54.6%), "ambiguity of the professional role of pharmacists" (54.6%) and "lack of scientific evidence of OTC TCM" (45.4%). The three main actions considered most relevant to improving pharmaceutical service of OTC TCM were "formulating or refining legislation to clarify the legal and professional role of pharmacists with respect to TCM" (60.7%), "strengthening training of pharmacists with respect to TCM" (57.9%), and "promoting public awareness of the pharmacist's role" (53.6%). According to the results of Chi-test, respondents' perceptions about the attitude, practice, perceived barriers, and improvement suggestions were significantly different depending on the education levels, certificate types and workloads of western medicine. CONCLUSIONS: The community pharmacists in Harbin, China were positive about the provision of OTC TCM pharmaceutical services. However, they were less certain about taking this duty as their primary responsibility. Insufficient knowledge and lack of role definition in the area of OTC TCM were found to be the major factors discouraging the provision of pharmaceutical service on OTC TCM by community pharmacists.

A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12.

BACKGROUND & AIMS: Older diabetic people are at risk of cognitive decline. Vitamin B12 deficiency in older people is associated with cognitive impairment and Alzheimer's disease. Vitamin B12 deficiency may therefore contribute to cognitive decline in older diabetic people. We therefore performed a randomized placebo-controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with mild vitamin B12 deficiency. METHODS: 271 diabetic non-demented outpatients aged 70 years or older with plasma vitamin B12 150-300 pmol/L in outpatient clinics were randomly assigned to take either methylcobalamin 1000 µg or two similar looking placebo tablets once daily for 27 months. All subjects were followed up at 9 monthly intervals. The primary outcome is cognitive decline as defined by an increase in clinical dementia rating scale (CDR) global score. The secondary outcomes included Neuropsychological Test Battery (NTB) z-scores, serum methymalonic acid (MMA) and homocysteine. RESULTS: The subjects in the trial groups were well matched in clinical characteristics, except that active intervention group had more smokers. 46.5% and 74.1% had elevated serum methymalonic acid (≥0.21 µmol/L) and homocysteine (≥13 µmol/L) respectively. 44% of the subjects had CDR score of 0.5 suggesting questionable dementia. At month 9 and 27, serum MMA and homocysteine was significantly reduced in the active treatment group, when compared with placebo group. (P < 0.0001, student t test) At month 27, there was no significant group difference in changes in CDR or NTB z-scores. Exclusion of smokers did not alter the results. Subgroup analysis of high MMSE and serum MMA showed similar results. CONCLUSION: Vitamin B12 supplementation did not prevent cognitive decline in older diabetic patients with borderline vitamin B12 status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02457507.

Challenges for drug discovery and development in China.

INTRODUCTION: The drug development industry is restructuring worldwide in terms of the research and development process. As with pharmaceuticals in the west, China faces major challenges for drug discovery and development. Areas covered: In this review, the authors discuss anti-cancer, anti-allergy, anti-infectious, and proprietary Chinese Medicines (pCM) for various chronic diseases (such as the allergic diseases: eczema, asthma and allergic rhinitis), which remain the contemporary therapeutic strategies that are being explored and developed. Drug transporters, disease specific biomarkers, pharmacophores, bioactive natural products and pharmacogenetics are some aspects of research technologies. Proprietary Chinese medicine remains one of the most popular strategies. There is however the issue of good research documentation of efficacy versus adverse effects. China has a complex healthcare system involving a large patient pool. Expert opinion: Various factors can impact drug development in China including the concurrent use of both western and Chinese medicines, pharmacogenetic variances, lack of multidisciplinary team impact on disease management and drug safety. China may adopt the current development of big data analysis in other countries such as UK and US to build and centralize a nationwide database for better monitoring and clinical evaluation to provide more efficient care at a lower cost.

A Matrix Mentoring Model That Effectively Supports Clinical and Translational Scientists and Increases Inclusion in Biomedical Research: Lessons From the University of Utah.

Physician-scientists and scientists in all the health professions are vital members of the U.S. biomedical workforce, but their numbers at academic health centers are declining. Mentorship has been identified as a key component in retention of faculty members at academic health centers. Effective mentoring may promote the retention of clinician-scientists in the biomedical workforce. The authors describe a holistic institutional mentoring program to support junior faculty members engaged in clinical and translational science at the University of Utah. The clinical and translational scholars (CATS) program leverages the resources of the institution, including the Center for Clinical and Translational Science, to augment departmental resources to support junior faculty investigators and uses a multilevel mentoring matrix that includes self, senior, scientific, peer, and staff mentorship. Begun in the Department of Pediatrics, the program was expanded in 2013 to include all departments in the school of medicine and the health sciences. During the two-year program, scholars learn management essentials and have leadership training designed to develop principal investigators. Of the 86 program participants since fiscal year 2008, 92% have received extramural awards, 99% remain in academic medicine, and 95% remain at the University of Utah. The CATS program has also been associated with increased inclusion of women and underrepresented minorities in the institutional research enterprise. The CATS program manifests institutional collaboration and coordination of resources, which have benefited faculty members and the institution. The model can be applied to other academic health centers to support and sustain the biomedical workforce.

Patient acceptability, efficacy, and skin biophysiology of a cream and cleanser containing lipid complex with shea butter extract versus a ceramide product for eczema.

OBJECTIVES: To investigate patient acceptability, efficacy, and skin biophysiological effects of a cream/cleanser combination for childhood atopic dermatitis. SETTING: Paediatric dermatology clinic at a university teaching hospital in Hong Kong. PATIENTS: Consecutive paediatric patients with atopic dermatitis who were interested in trying a new moisturiser were recruited between 1 April 2013 and 31 March 2014. Swabs and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORing Atopic Dermatitis index), skin hydration, and transepidermal water loss were obtained prior to and following 4-week usage of a cream/cleanser containing lipid complex with shea butter extract (Ezerra cream; Hoe Pharma, Petaling Jaya, Malaysia). Global or general acceptability of treatment was documented as 'very good', 'good', 'fair', or 'poor'. RESULTS: A total of 34 patients with atopic dermatitis were recruited; 74% reported 'very good' or 'good', whereas 26% reported 'fair' or 'poor' general acceptability of treatment of the Ezerra cream; and 76% reported 'very good' or 'good', whereas 24% reported 'fair' or 'poor' general acceptability of treatment of the Ezerra cleanser. There were no intergroup differences in pre-usage clinical parameters of age, objective SCORing Atopic Dermatitis index, pruritus, sleep loss, skin hydration, transepidermal water loss, topical corticosteroid usage, oral antihistamine usage, or general acceptability of treatment of the prior emollient. Following use of the Ezerra cream, mean pruritus score decreased from 6.7 to 6.0 (P=0.036) and mean Children's Dermatology Life Quality Index improved from 10.0 to 8.0 (P=0.021) in the 'very good'/'good' group. There were no statistically significant differences in the acceptability of wash (P=0.526) and emollients (P=0.537) with pre-trial products. When compared with the data of another ceramide-precursor moisturiser in a previous study, there was no statistical difference in efficacy and acceptability between the two products. CONCLUSIONS: The trial cream was acceptable in three quarters of patients with atopic dermatitis. Patients who accepted the cream had less pruritus and improved quality of life than the non-accepting patients following its usage. The cream containing shea butter extract did not differ in acceptability or efficacy from a ceramide-precursor product. Patient acceptability is an important factor for treatment efficacy. There is a general lack of published clinical trials to document the efficacy and skin biophysiological effects of many of the proprietary moisturisers.

Correlations among steroid fear, acceptability, usage frequency, quality of life and disease severity in childhood eczema.

UNLABELLED: Topical corticosteroids (CSs) are the mainstay of treatment for eczema but CS phobia and fears are prevalent and influence therapeutic efficacy. AIM: To quantify if CS acceptability and fear affect patients' quality-of-life (QoL). METHODS: Patients with eczema managed in the pediatric dermatology outpatient clinic of a university hospital were surveyed. Nottingham Eczema Severity Score (NESS) for severity, Children's Dermatology Life Quality Index (CDLQI) for QoL, CS fear, acceptability and reported frequency of CS use were measured with quantified questions. RESULTS: CS fears were prevalent among parents and caregivers of patients with eczema. Fifty-eight percent of parents reported general acceptability of CS as being very good or good, and many applied CS to their child regularly every week. However, >40% of parents reported CS fear "always" or "often", 41% reported that they "always" or "often" apply CS only when eczema got worse, 57% would discuss CS fear with their doctors, 30% would request CS-sparing medications and 14% "always" or "often" use traditional Chinese herbal medicine. Fears were predominantly interpersonal and less often iatrogenic in nature. Skin problems were the most concerned side effects of CS. CS acceptability, frequency of CS usage, CS fear and usage of alternative medications were independent domains in eczema management: CS fears correlated with CDLQI; CS usage frequency correlated with NESS and negatively with parental education; and CS acceptability correlated with parental education. Ordinal logistic regressions showed worse QoL was associated with more CS fear (odds ratio: 1.092 [95% CI: 1.023-1.165], p = 0.008). CONCLUSIONS: The extent of CS fears is independent of CS acceptability, but correlates with patients' QoL. Desensitization of parental CS fears should be integral part of eczema education and therapeutics in order to improve therapeutic efficacy and patients' QoL.

A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders.

OBJECTIVE: To evaluate whether pretreatment dehydroepiandrosterone (DHEA) supplementation improves ovarian response markers, ovarian response to standard low-dose gonadotropin stimulation, and in vitro fertilization (IVF) outcomes in poor responders. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Tertiary reproductive medicine unit. PATIENT(S): Thirty-two women with anticipated poor ovarian response. INTERVENTION(S): Randomization into DHEA group (n=16) receiving GNC (25 mg three times a day) or placebo (n=16) starting from at least 12 weeks before the scheduled IVF treatment according to a computer-generated randomization list. MAIN OUTCOME MEASURE(S): Measurement of monthly ovarian response markers, including antral follicle count (AFC), serum antimüllerian hormone (AMH), and follicle-stimulating hormone (FSH) levels; comparison of ovarian response to a standard dose of gonadotropin stimulation at week 8 and IVF outcomes; and AFC after 12 weeks (primary outcome). RESULT(S): The DHEA supplementation resulted in statistically significantly higher serum DHEA-S, free androgen index, and follicular DHEA-S levels. No statistically significant differences in the ovarian response markers (AFC, AMH, or FSH), the ovarian response to standard-dose gonadotropin stimulation, or IVF outcomes were found between the two groups. CONCLUSION(S): No statistically significant improvement in ovarian response markers, ovarian response to standard dose gonadotropin stimulation, or IVF outcomes was found in poor responders receiving pretreatment DHEA. CLINICAL TRIAL REGISTRATION NUMBER: HKCTR-1149 (www.hkclinicaltrials.com) and NCT01915186 (www.ClinicalTrials.org).

Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy.

OBJECTIVES: The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis. METHODS: This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis. RESULTS: A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups. CONCLUSIONS: High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.

Ibandronate increases cortical bone density in patients with systemic lupus erythematosus on long-term glucocorticoid.

INTRODUCTION: The purpose of this research is to assess the effects of oral ibandronate on bone microarchitecture by using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with systemic lupus erythematosus (SLE) taking a long-term glucocorticoid. METHODS: In this double-blind placebo-controlled study, 40 Chinese female SLE patients taking prednisolone were randomly assigned to receive either monthly oral ibandronate (150 mg) or placebo with daily 1-hydroxycholecalciferol (Alfacalcidol; 1 µg) and calcium supplement for 12 months. Assessments of bone microarchitecture by using HR-pQCT and area bone mineral density (aBMD) of the lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) were performed at baseline and 12 months. RESULTS: No differences in baseline characteristics were found between the two groups. After 12 months, no statistical differences were noted in any of the bone densities, microarchitectural parameters, or percentage changes of these parameters, as measured with HR-pQCT or DXA between the two groups. However, within the active group, the percentage improvement was significant in cortical bone density (P = 0.023) which was absent in the placebo group. Improvement was also seen in the aBMD of both the lumbar spine (P < 0.0001) and the hip (P < 0.005). In the placebo group, the percentage increase in trabecular separation was significant (P = 0.04), and the percentage improvement in aBMD in the spine also was significant (P = 0.049). CONCLUSIONS: Oral ibandronate treatment improves microarchitecture in SLE patients taking long-term glucocorticoid assessed with HR-pQCT, and this new technology may have a role in assessing bony changes in future longitudinal studies in SLE patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00668330.