Fischer, Philip R.

Abstract Context Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets. Objective To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children. Methods We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score. Results A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ± 29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ± 87 and 214 ± 96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ± 415 and 245 ± 78 U/L, respectively (P < 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = −0.34; P < 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP > 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07. Conclusion An AP > 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies.

AbstractThiamine deficiency has been typically associated with alcoholism or as a prevalent problem in low‐ and middle‐income countries (LMICs) whose populations rely on staple foods with a low content of thiamine. We conducted a literature review of published and unpublished data to identify relevant adult cases with confirmed thiamine deficiency of nonalcoholic cause in developed countries. We selected 17 reports with 81 adult cases of confirmed thiamine deficiency affecting adult patients with a wide range of ages and underlying conditions (e.g., cancer, gastrointestinal diseases, heart failure, and obesity). Thiamine deficiency may have been caused by disease‐related malnutrition, bariatric surgery, chronic use of diuretics, repeated vomiting, lack of thiamine in parenteral nutrition formulas, food insecurity, and reliance on monotonous or restrictive diets. Treatment with intravenous thiamine resulted in partial or complete recovery from the symptoms (cardiac, neurologic, and metabolic disorders) for most patients. The number and variety of symptomatic thiamine‐deficient adults identified in this review demonstrates that thiamine deficiency is not exclusive to LMICs and, in high‐income settings, is not exclusive to alcoholic patients. In developed countries, this serious but treatable condition can be expected in patients suffering from various medical conditions or following certain dietary patterns.

Abstract Thiamine is an essential water‐soluble vitamin that plays an important role in energy metabolism. Thiamine deficiency presents many challenges to clinicians, in part due to the broad clinical spectrum, referred to as thiamine deficiency disorders (TDDs), affecting the metabolic, neurologic, cardiovascular, respiratory, gastrointestinal, and musculoskeletal systems. Concurrent illnesses and overlapping signs and symptoms with other disorders can further complicate this. As such, TDDs are frequently misdiagnosed and treatment opportunities missed, with fatal consequences or permanent neurologic sequelae. In the absence of specific diagnostic tests, a low threshold of clinical suspicion and early therapeutic thiamine is currently the best approach. Even in severe cases, rapid clinical improvement can occur within hours or days, with neurological involvement possibly requiring higher doses and a longer recovery time. Active research aims to help better identify patients with thiamine‐responsive disorders and future research is needed to determine effective dosing regimens for the various clinical presentations of TDDs. Understanding the clinical diagnosis and global burden of thiamine deficiency will help to implement national surveillance and population‐level prevention programs, with education to sensitize clinicians to TDDs. With concerted effort, the morbidity and mortality related to thiamine deficiency can be reduced.

A functional disorder is a constellation of bothersome physical symptoms that compromise regular function but for which there is no identifiable organic or psychiatric pathology. Functional disorders can present with various symptoms. Common forms of functional disorders include functional neurologic symptom disorder (also referred to as “conversion disorder”), functional gastrointestinal disorders, chronic pain syndromes, and chronic fatigue. One-third to one-half of outpatient consultations in many practices are due to functional disorders. Functional disorders must be distinguished from structural and psychiatric disorders but should not be considered diagnoses of exclusion. Recovery is facilitated by good relationships between patients and practitioners, with good explanations of the pathophysiology of functional disorders and effective encouragement and education of patients.

Purpose: Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic treatment is inconsistent and unstandardized. We did a systematic review to identify controlled studies from which informed treatment decisions can be made. Method: Through a standard systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified all English-language studies of a medication treatment for postural orthostatic tachycardia syndrome that included a comparison or control group and followed outcomes for at least 1 week of treatment. Results: A total of 626 studies were identified by the search criteria, and 8, involving a total of 499 patients, met the criteria. No studies were adequately similar to allow for meta-analysis. Of the identified 8 studies, 2 were randomized controlled trials and 4 had been subjected to peer review. In individual studies, there was some favorable effect with fludrocortisone, beta blockers, midodrine, and selective serotonin reuptake inhibitors. Conclusion: There is a paucity of high-quality data about effectiveness of medication in the treatment of postural orthostatic tachycardia syndrome. Nonetheless, 2 randomized trials and 6 other reports show some favorable effects of medication.

AbstractObjectiveOrthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70‐degree head‐up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility.Study designFrom medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation.ResultsTwo hundred twenty‐nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests.ConclusionGI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.