Diagnostic and New Therapeutic Approaches to Two Challenging Pediatric Metabolic Bone Disorders: Hypophosphatasia and X-linked Hypophosphatemic Rickets.

The diagnosis and management of metabolic bone disease among children can be challenging. This difficulty could be due to many factors, including limited awareness of these rare conditions, the complex pathophysiology of calcium and phosphate homeostasis, the overlapping phenotype with more common disorders (such as rickets), and the lack of specific treatments for these rare disorders. As a result, affected individuals could experience delayed diagnosis or misdiagnosis, leading to improper management. In this review, we describe the challenges facing diagnostic and therapeutic approaches to two metabolic bone disorders (MBD) among children: hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). We focus on explaining the pathophysiological processes that conceptually underpin novel therapeutic approaches, as well as these conditions' clinical or radiological similarity to nutritional rickets. Particularly in areas with limited sun exposure and among patients not supplementing vitamin D, nutritional rickets are still more common than HPP and XLH, and pediatricians and primary physicians frequently encounter this disorder in their practices. More recently, our understanding of these disorders has significantly improved, leading to the development of novel therapies. Asfotas alfa, a recombinant, human-tissue, nonspecific alkaline phosphatase, improved the survival of patients with HPP. Burosumab, a human monoclonal anti-FGF23 antibody, was recently approved as a specific therapy for XLH. We also highlight the current evidence on these two specific therapies' safety and effectiveness, though long-term data are still needed. Both HPP and XLH are multisystemic disorders that should be managed by multidisciplinary teams. Finally, recognizing these conditions in early stages will enable affected children and young adults to benefit from newly introduced, specific therapies.

Subclinical Neuropathy in Children With Type I Diabetes Mellitus: Tertiary Care Centre Experience.

INTRODUCTION: Diabetic peripheral neuropathy is a common complication of diabetes mellitus (DM) type 1. However, it can occur without evidence of symptoms or clinical signs of neuropathy labeled as subclinical neuropathy, which neurophysiological studies can best detect. PURPOSE: To evaluate the prevalence of subclinical neuropathy among children with DM type 1, determine the association with blood sugar control, and evaluate the pattern of nerve involvement in neurophysiological studies. METHODS: This cross-sectional study evaluated 100 children with DM type 1, aged five to 15 years, at least one year after the diagnosis. Subclinical neuropathy was evaluated using nerve conduction study. Glycemic control was assessed using hemoglobin A1c (HbA1c). RESULTS: The mean age of subjects was 11.5 ± 0.25 years. The average age at the onset of the disease was 5.95 ± 0.25 years. There were 64 patients who had electrophysiological evidence of peripheral neuropathy. The most observed electrophysiological changes were distal latency abnormalities in the left and right peroneal nerves in 39 and 33 patients, respectively. Sensory nerve amplitude, peak latency, and conduction velocity were normal in all patients (100%). HbA1c level did not show a statistically significant association with the incidence of subclinical neuropathy. CONCLUSION: Subclinical neuropathy was prevalent in children with DM type 1. Poor glucose control was only associated with an increased odds ratio of subclinical neuropathy.

Does physician distraction lead to diagnostic and management errors? An exploratory study in the primary care setting.

OBJECTIVES: There is an increasing concern about diagnostic errors and their impact on patient safety. Physicians' diagnostic ability is significantly undermined by certain distractions that can carry potential negative consequences such as diagnostic and management errors. This study aimed to examine the effects of distracting factors for physicians during consultation and their consequent effects on diagnostic accuracy and disease or condition management. METHODS: Family medicine residents at a major training hospital in KSA were randomly assigned to two groups of simulated patients: one group with patients with distracting features and another group with patients without distracting features (the control group). Both groups encountered six simulated patients with different clinical conditions or diseases. The consultation time, accuracy of diagnosis, appropriateness of management, number of outlines of treatment, and simulated patient satisfaction were measured for both groups. RESULTS: A total of 70 simulated physician-patient encounters were conducted with 35 residents. Consultation time was significantly longer for encounters with patients with distracting features, which had a mean time of 7.43 min, compared with encounters with non-distracting patients, which had a mean time of 4.4 min (p value < 0.0001). There were no significant statistical differences in accuracy of diagnosis, appropriateness of management, or patient satisfaction between the two groups. However, residents recommended a higher number of outlines of treatment for patients with distracting features (2.96 for distracting patients versus 2.46 for non-distracting patients; p < 0.011). CONCLUSION: Distracting factors are associated with prolonged consultation time among physicians. Although this study did not demonstrate any effects of distracting factors on accuracy of diagnosis or disease management, these factors are still concerning, especially in complex clinical situations and situations where there is lack of reflective practice. The effects of distracting factors should be minimized to ensure patient safety.

Does Time Pressure Have a Negative Effect on Diagnostic Accuracy?

PURPOSE: Studies suggest time pressure has negative effects on physicians' working conditions and may lead to suboptimal patient care and medical errors. Experimental evidence supporting this is lacking, however. This study investigated the effect of time pressure on diagnostic accuracy. METHOD: In 2013, senior internal medicine residents at three hospitals in Saudi Arabia were divided randomly into two groups: a time-pressure condition and a control condition without time pressure. Both groups diagnosed eight written clinical cases presented on computers. In the time-pressure condition, after completing each case, participants received information that they were behind schedule. Response time was recorded, and diagnostic accuracy was scored. RESULTS: The 23 participants in the time-pressure condition spent significantly less time diagnosing the cases (mean = 96.00 seconds) than the 19 control participants (mean = 151.97 seconds) (P < .001). Participants under time pressure had a significantly lower diagnostic accuracy score (mean = 0.33; 95% CI, 0.23-0.43) than participants without time pressure (mean = 0.51; 95% CI, 0.42-0.60) (F[1, 41] = 6.90, P = .012, η = 0.15). This suggests participants in the time-pressure condition made on average 37% more errors than control participants. CONCLUSIONS: Time pressure has a negative impact on diagnostic performance. The authors propose that the effect of time pressure on diagnostic accuracy is moderated by both the case difficulty level and the physician's level of experience. Post hoc analyses demonstrated that time pressure affects diagnostic accuracy only if cases are not too difficult and physicians' expertise level is intermediate.

Age- and gender-specific reference intervals for serum lipid levels (measured with an Advia 1650 analyzer) in school children.

BACKGROUND: Due to the lack of country-specific norms in Saudi Arabia, age- and gender-specific lipid reference intervals are needed to be established for Saudi children. METHODS: Blood samples were collected from 1168 children aged 6-16 years: 500 boys (43%) and 668 girls (57%), and were analyzed for cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Reference intervals were established by calculating the mean and the 2.5th and 97.5th percentiles. RESULTS: There were significant differences between boys at each Tanner stage with respect to cholesterol (P < 0.001); and HDL (P < 0.0001) but not LDL (P < 0.06) among girls. There were significant differences between boys and girls during puberty with respect to cholesterol (P < 0.0001), HDL (P < 0.0001), and LDL (P < 0.001). There was a significant positive correlation between total cholesterol levels, LDL and HDL levels at all Tanner stages in both genders. In girls, the only significant inverse correlation was at stage I (r=-0.243, P= 0.001); there was no significant correlation at other stages. CONCLUSIONS: Unlike children in other developing countries, Saudi children do not have lower serum cholesterol than their Western counterparts. These findings reflect changing dietary habits and increasing affluence in Saudi Arabia. These reference intervals may be used to aid in the early assessment of cardiovascular risk in Saudi pediatric populations.

Two siblings with familial chylomicronemia syndrome: disease course and effectiveness of early treatment.

There are no adequate data that evaluate the safety and effectiveness of lowering triglyceride levels in very young children. The authors report a family with two male siblings, 7 and 4 years old, affected by familial hyperchylomicronemia. The oldest was diagnosed at birth during evaluation of jaundice, and the youngest showed asymptomatic hypertriglyceridemia by 6 months of age. Due to high triglyceride levels, Gemfibrozil (a fibric acid derivative) was started at diagnosis. Close clinical followup and laboratory monitoring of these children showed no side effects from the drug, and the risk of acute pancreatitis was significantly reduced.