Medical treatment of weight loss in children and adolescents with obesity.

Obesity remains one of the biggest health problems both in adults and children. Lifestyle modification, including diet and exercise, continues to be the mainstay of obesity prevention and treatment. Unfortunately, lifestyle modifications are often unsuccessful. Pharmacological treatment of obesity in pediatric patients can be applied in selected cases, and not before evidence of failure of the multidisciplinary lifestyle intervention. In this narrative review, we revised the most up-to-date evidence on medical treatment of weight loss in children and adolescents with obesity, including FDA- or EMA-approved and -experimented, not approved, drugs for pediatric population. Multidisciplinary treatment of childhood obesity, regulation of appetite control, energy balance and body weight were also discussed, in order to clarify the indications and mechanism action of drugs. Despite a substantial number of medications used for the treatment of obesity in adults, a limited number of drugs are approved by the drug regulatory agencies for pediatric population. Further research is needed to evaluate the efficacy and safety of novel pharmacological approaches for treatment of pediatric obesity in order to optimize weight management for children and adolescents and limit the development obesity-related comorbidities.

Beta-blocker-associated hypoglycaemia: New insights from a real-world pharmacovigilance study.

AIMS: To investigate the statistical association between hypoglycaemia and ß-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence. METHODS: We investigated the relationship between pharmacological parameters of ß-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association. RESULTS: Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for ß1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20). CONCLUSION: Nadolol appears to be the ß-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective ß-blockers seem to increase the risk for its occurrence.

Severe hypoglycemia in children treated with nadolol: A case report and FDA adverse event reporting system (FAERS) database analysis.

OBJECTIVE: We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with ß-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known. MATERIALS AND METHODS: We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication. RESULTS: Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age: 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases. CONCLUSION: Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.

Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review.

Aim: to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event. Methods: we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting. Results: A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3-5)], compared to 15 (9-18) vs. 10 (6-18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance (p > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized. Conclusion: Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians' awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.

HPV Vaccination in Young Males: A Glimpse of Coverage, Parental Attitude and Need of Additional Information from Lombardy Region, Italy.

Background: In the Lombardy Region, Italy, HPV vaccination is recommended and offered free of charge to 12-years-old males since 2017. The expected vaccination thresholds are still far to be reached. Methods: A cross-sectional survey to investigate parents' attitudes towards the HPV vaccine and knowledge about HPV was administered to parents of boys aged 6 to 18 years attending a large pediatric hospital for outpatient specialistic evaluations. Two parallel multiple logistic regression analyses were conducted to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for attitude towards HPV vaccination and perceived need for more information about HPV vaccination. Results: A positive attitude towards HPV vaccination was found in 74% of interviewed parents. Knowledge of HPV, having a generally positive attitude toward vaccination, and mothers filling in the survey were positively associated with a positive attitude to the HPV vaccine. Parents' perceived need for more information about HPV vaccination was positively associated with the child's age, general positive attitude toward vaccination, Christian religion, and positive attitude toward HPV vaccination; knowing that HPV vaccination is free of charge significantly reduced the risk of asking for more information on HPV vaccination. Conclusions: The majority of parents of male children and adolescents in our study have a positive attitude toward HPV vaccination. Attitude toward HPV vaccination and perceived need for more information on HPV vaccination were directly related to a positive attitude toward vaccines in general. In addition, knowledge of HPV and related pathologies favors a positive attitude toward HPV vaccination. Future health programs should target an even wider diffusion of evidence-based information on vaccines in general and on the HPV vaccine in young males, to support a positive attitude toward vaccines in the general population.

Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight.

Acanthosis nigricans (AN) is associated with obesity and type 2 diabetes, where insulin resistance (IR) is considered a predisposing factor. IR can also affect patients with type 1 diabetes (T1D). We evaluated the prevalence of AN in patients with T1D compared to subjects with obesity in order to define the interplay between IR and excess weight. We considered 138 pediatric patients who presented with T1D and 162 with obesity. As controls, 100 healthy normal-weight subjects were included. A physical examination with the detection of AN and biochemical assessments was performed. IR was calculated by using the homeostasis model assessment for IR in patients with obesity and the estimated glucose disposal rate in T1D. The AN prevalence was higher in T1D and obese subjects compared with controls in whom AN was not detected (p = 0.02 and p < 0.001, respectively). A greater number of AN cases were observed in subjects with obesity compared with T1D (p < 0.001). Patients with AN were older than subjects without AN (p = 0.005), and they had higher body mass index (BMI) values, waist circumference (WC), fasting triglycerides and blood pressure (all p < 0.001). Thirty-five patients with AN exhibited IR with an association between AN presence and IR in patients with obesity (p < 0.001). In T1D, there was an association between AN and being overweight/obese (p = 0.02), independently of IR. AN is a dermatological condition associated with obesity. In T1D, the presence of AN was significantly associated with overweight status or obesity but not IR. The presence of AN in the absence of IR supports the interplay role between impaired insulin signaling, IR and excess weight in the pathogenic mechanism.