Cardiac and metabolic safety profile of antipsychotics in youths: A WHO safety database analysis.

A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We aimed to assess age-dependent reporting of cardiac and metabolic disorders in youths, relying on the WHO safety database (VigiBase®). VigiBase® was queried for all reports of cardiac, glucose, lipid and nutritional disorders involving APs. Patients <18 years were classified as pediatric population. Disproportionality analyses relied on the Information Component (IC): the positivity of the lower end of its 95 % confidence interval was required to suspect a signal. We yielded 4,672 pediatric reports. In disproportionality analysis, nutritional disorders were leading in youths (IC 3.9 [3.9-4.0]). Among healthcare professionals' reports, stronger signals were detected in youths than in adults. Children had the greatest signal with nutritional disorders (IC 4.7 [4.6-4.8]). In adolescents, aripiprazole was ascribed to non-alcoholic steatohepatitis (NASH). Our findings, based on real-world data, support the hypothesis of a greater propensity for nutritional disorders in youths, despite limitations of pharmacovigilance studies. We suggest specific safety profiles, such as aripiprazole and NASH. Pending more answers from population-based studies, a careful anamnesis should seek for risk factors before AP initiation. A cautious monitoring is warranted to allow earlier identification of side effects.

Changes in clinical trials of endocrine disorder and metabolism and nutrition disorder drugs in mainland China over 2010-2019.

With the improvements in relevant policies, laws, and regulations regarding drug clinical trials in China, the quantity and quality of drug clinical trials have gradually improved, and the development prospects of drug clinical trials for endocrine disorders and metabolism and nutrition disorders are promising. Based on information from the clinical trials from the online drug clinical trial registration platform of the National Medical Products Administration, we aimed to review and evaluate the development of clinical trials of drugs for endocrine disorders and metabolism and nutrition disorders in mainland China from 2010 to 2019, as well as the trends over time. A total of 861 trials were carried out on 254 types of drugs for endocrine disorders and metabolism and nutrition disorders, among which 531 (61.67%) involved endocrine disorders, and 330 (38.33%) addressed metabolism and nutrition disorders. The annual number of clinical trials has been increasing gradually, with a significant increase in 2017. Among them, the proportion of clinical trials with Chinese epidemiological characteristics was relatively large (Wu, Annual Report on Development Health Management and Health Industry in China, 2018). The largest number of trials were for diabetes drugs (55.63%), followed by trials of drugs for hyperlipidemia (19.4%) and those for hyperuricemia (7.9%). It was found that the geographical area of the leading units also showed obvious unevenness according to the analysis of the test unit data. Based on the statistics and evaluation of the data, comprehensive information is provided to support the cooperation of global pharmaceutical R&D companies and research units in China and the development of international multicenter clinical trials in China. This work additionally provides clinical trial units with a self-evaluation of scientific research competitiveness and hospital development strategies. At the same time, it provides a reference with basic data for sponsors and stakeholders in these trials to determine their development strategy goals.

Case Report: Nutritional and Toxic Optic Neuropathy: A Diagnostic Dilemma.

SIGNIFICANCE: Nutritional and toxic optic neuropathies are rare disorders characterized by visual impairment due to optic nerve damage by a toxin, usually with coexisting nutritional deficiencies. Its pathophysiology is still unclear, and multiple mechanisms implicated act synergistically to bring about this condition. The decline in its incidence and its confusing clinical appearance make diagnosing nutritional and toxic optic neuropathies challenging. PURPOSE: This is an observational clinical case report of an atypical clinical case of a nutritional and toxic optic neuropathy with a subacute presentation and papilledema at the time of diagnosis. The patient provided written informed consent for medical information and images to be published. CASE REPORT: A 47-year-old man presented with progressive, painless bilateral decrease in central vision over 15 days. The patient had a long-standing history of alcohol abuse and was a heavy smoker. The examination revealed dyschromatopsia, 20/400 visual acuity on both eyes, and no relative afferent pupillary defect. Funduscopy revealed bilateral papilledema. A visual field test showed generalized depression with centrocecal involvement in the left eye. Laboratory studies evidenced decreased vitamin B12/B1 and red blood cell folate levels, increased acute phase reactants, hypertransaminasemia, and macrocytic anemia. Serologies and methanol in urine were negative. After the discontinuation of tobacco use and alcohol accompanied by vitamin supplementation, our patient's visual field, visual acuity, and papilledema improved remarkably. After 5 months, visual acuity and funduscopy were normal. CONCLUSIONS: Although some hallmark signs were visible in this case, its subacute presentation and the presence of papilledema at diagnosis caused some diagnostic uncertainty. Nutritional and toxic optic neuropathy is a rare and challenging diagnosis because of a lack of biomarkers. Eye care clinicians should consider nutritional and toxic optic neuropathies to prevent severe and irreversible visual damage resulting from underdiagnosis and mismanagement.

Probiotics as a Tx resource in primary care.

While probiotics have not been marketed as drugs, clinicians can still recommend them in an evidence-based manner.

Application of Acyzol in the Context of Zinc Deficiency and Perspectives.

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.

Risks of the 'Sunshine pill' - a case of hypervitaminosis D.

Vitamin D is a fat-soluble vitamin essential for calcium homeostasis and bone health. Vitamin D toxicity or hypervitaminosis D is extremely rare. We describe the case of a 73-year-old man who presented with life-threatening hypervitaminosis D and hypercalcaemia resulting from self-medicated doses of vitamin D supplements. This case, alongside other global case reports, highlights the potential dangers of unlicensed vitamin D replacement. We discuss the evidence for vitamin D replacement and remind readers of the current guidance on daily intake and supplementation.

Acute nutritional axonal neuropathy.

INTRODUCTION: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. METHODS: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. RESULTS: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. DISCUSSION: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018.

Reversible vascular calcifications associated with hypervitaminosis D.

A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

Iron deficiency anemia presenting with macular star.

We report the case of 16-year-old girl who presented with sudden painless decreased vision in her right eye of 5 days' duration. Anterior segment examination in both eyes showed conjunctival pallor. Results of ophthalmoscopic examination and optical coherence tomography were consistent with macular preretinal hemorrhage in both eyes with macular star in the left eye. Hematologic investigation disclosed severe iron deficiency anaemia. After 2 months, with oral substitution therapy with ferrous ascorbate and improved iron levels, the patient's visual acuity improved and macular preretinal hemorrhage resolved in both eyes.

A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy.

BACKGROUND: Megestrol acetate (MA) is an appetite stimulant with efficacy in promoting weight gain in adults with cancer-associated anorexia-cachexia. Studies documenting MA efficacy in children, however, are limited. We present the first randomized, double-blind, placebo-controlled clinical trial of MA versus placebo in children with cancer and weight loss. METHODS: Subjects <18 years of age with weight loss (minimum 5% from highest previous weight; or %ideal body weight <90%) due to cancer and/or cancer therapy were randomized to either MA (7.5 mg/kg/day) or placebo for a planned study duration of 90 days. Primary outcome was the difference between groups in mean percent weight change from beginning to end of the study period. Secondary outcomes included effects on anthropometrics, body composition, need for tube feeding or parenteral nutrition, and toxicities. RESULTS: Twenty-six patients were randomly assigned (13 MA, 13 placebo). The MA group experienced a mean weight gain of +19.7% compared to a mean weight loss of -1.2% in the placebo group, for a difference of +20.9% (95%CI: +11.3% to +30.5%, P = 0.003) in favor of MA over placebo. MA subjects experienced significant increases in weight for age z-scores, body mass index z-scores, and mid upper arm circumference compared to placebo. DXA scanning suggested disproportionate increases in fat accrual. Adrenal suppression was the main toxicity of MA. CONCLUSION: In children with high-risk malignancies, MA resulted in significant increases in mean percent weight change compared to placebo. Further studies of MA should be pursued to better delineate the effect on nutritional status.

The discovery and characterization of riboflavin.

The first observation of a pigment in milk with yellow-green fluorescence can be traced to the English chemist Alexander Wynter Blyth in 1872, but it was not until the early 1930s that the substance was characterized as riboflavin. Interest in accessory food factors began in the latter half of the 19th century with the discovery of the first vitamin, thiamin. Thiamin was water soluble and given the name vitamin B(1). However, researchers realized that there were one or more additional water-soluble factors and these were called the vitamin B-2 complex. The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s. As there is no classical nutritional disease attributable to riboflavin deficiency, it was the growth-stimulating properties of the food extracts given to young rats that provided the tool with which to investigate and eventually extract riboflavin. Riboflavin was the second vitamin to be isolated and the first from the vitamin B-2 complex; the essential nature of the vitamin as a food constituent for man was shown in 1939.

Iron deficiency in women: assessment, causes and consequences.

PURPOSE OF REVIEW: Iron deficiency is the most common nutritional disorder affecting about 20-25% of the world's population, predominantly children and women. There is emerging evidence that depletion of iron stores may have adverse consequences for adults even in the absence of anaemia. This raises issues about the most appropriate method of assessing iron status. RECENT FINDINGS: Although the effects of iron-deficiency anaemia are well characterized, emerging evidence suggests that iron deficiency without anaemia can have negative consequences in adults, particularly for neurocognitive outcomes. Iron deficiency is more likely in women of reproductive age because of menstrual blood loss. However, extremes of blood loss such as regular blood donation, diets of low bioavailability and the challenges of pregnancy all markedly increase the risk of iron deficiency. In addition, the physiological changes in pregnancy affect the normal reference ranges used in laboratory assessment. The use of haemoglobin as a marker of iron deficiency is limited by its low specificity and sensitivity and although the use of alternative biomarkers is becoming more common, interpreting results in conditions of chronic inflammation, including that associated with increased adiposity, needs more investigation. SUMMARY: By understanding the physiology of iron metabolism alongside the limitations and interpretation of biomarkers of iron deficiency, clinicians and nutritionists are better equipped to identify changes in iron balance and to further investigate the functional outcomes of iron deficiency.

Metabolic, renal, and nutritional consequences of bariatric surgery: implications for the clinician.

Management of obesity-associated comorbidities costs about $60 billion/year, about 5% of total US healthcare expenditure. Bariatric surgery is the only proven effective weight loss therapy for severely obese patients with a BMI > or =35 kg/m2. Bariatric surgery produces long-term weight loss, improves quality of life, and reduces the number of sick days and medication costs. Surgery has a profound effect on the metabolic milieu and nutritional status from the first few days after surgery, even before significant weight loss has been achieved. Metabolic effects of bariatric surgery reduce obesity-related comorbidities like type 2 diabetes, hypertension, metabolic syndrome, and cardiovascular disease risk. Improvement in renal function is seen, but adverse effects like oxalate nephropathy can lead to chronic kidney disease or end-stage renal disease (CKD/ESRD). Surgery can also lead to micronutrient deficiencies, making dietary supplementation necessary. Reduction in insulin resistance and hypertension after surgery makes medication adjustment imperative. Improvement in comorbidities and nutritional deficiencies after bariatric surgery has important clinical implications.

Early INCAP longitudinal nutrition studies at the community level.

This paper reviews the findings of early field studies of INCAP comparing the effects of vitamin B12 and animal and vegetable protein on the growth of poorly nourished schoolchildren. It also describes a 5-year community-based intervention study showing that a protein-rich supplement given to preschool children improves growth and cognition and decreases morbidity and mortality. Medical care in one village had no detectable benefits. A classical seven-year community-based detailed observational study of the infection status and growth in children from birth is also summarized.

Melanotropins as drugs for the treatment of obesity and other feeding disorders: potential and problems.

Current biological and pharmacological evidence suggests that the melanocortin 4 and melanocortin 3 receptors which are seven transmembrane G-protein coupled receptors (GPCRs) are involved in various aspects of energy balance and feeding behaviors in animals including humans. The natural endogenous ligands for these receptors are products of the gene pro-opiomelanocortin (POMC), and include alpha-melanocyte stimulating hormone, gamma-melanocyte stimulating hormone and perhaps other modified products of POMC. Thus well designed agonists and antagonists of these ligands might serve as drugs for the treatment of feeding disorders. However, these melanotropin peptides also can have other biological activities that involve the MC3R and MC4R, and these other biological properties will need to be modulated in ligands that are likely to be useful drugs for feeding disorders. Current progress in these areas with special emphasis on the MC3R will be discussed along with possible new directions that might be fruitful in these important aspects of contemporary biology and medicine.

Correction of metabolic acidosis on serum albumin and protein catabolism in hemodialysis patients.

BACKGROUND: The effect of the correction of metabolic acidosis (MA) on serum albumin concentrations (sAlbs) in hemodialysis (HD) patients is controversial. This study evaluated the role of the correction of MA on sAlb concentrations, normalized protein catabolic rate (nPCR), and the effect of the concomitant inflammatory status, in a group of acidotic HD patients. METHODS: The correction of MA by oral supplementation with sodium bicarbonate, and the evaluation of its effect on sAlb, nPCR, and high-sensitivity C-reactive protein (hsCRP), were performed in 29 patients on bicarbonate dialysis for a median of 30 months. Other variables included pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, body weight, interdialytic weight gain, pre-HD systolic and diastolic blood pressure, and Kt/V. RESULTS: Serum bicarbonate and pH increased significantly (P < .0001), from 19.1 +/- 0.7 mmol/L to 24.6 +/- 1.1 mmol/L and from 7.33 +/- 0.03 to 7.39 +/- 0.02, respectively (all values with +/- are SD). The nPCR decreased from 1.13 +/- 0.14 g/kg/day to 1.05 +/- 0.14 g/kg/day (P < .0001). The other variables did not change significantly. In 17 patients with high-sensitivity C-reactive protein <10 mg/L, sAlb increased from 3.7 +/- 0.3 g/dL to 4.0 +/- 0.3 g/dL (P < .01), whereas in 12 with high-sensitivity C-reactive protein >or=10 mg/L, sAlb did not change (3.5 +/- 0.17 g/dL vs. 3.4 +/- 0.13 g/dL; P = NS). CONCLUSIONS: Oral sodium bicarbonate supplementation is effective in correcting MA in HD patients and does not affect interdialytic weight gain, plasma Na, and blood pressure. The correction of MA is effective in reducing protein catabolism (nPCR) in both inflamed and less inflamed HD patients, but increases sAlb only in patients without inflammation. In inflamed patients, the correction of MA is not sufficient per se to improve sAlb concentrations.