A meta-analytic review of six types of nonpharmacological interventions, including dietary and psychological treatments, for children with ADHD found positive effects on ADHD symptoms for all types ...when raters were aware of treatment allocation (unblinded conditions). However, when raters were blinded, statistically significant effects on ADHD symptoms were found only for supplementation with omega-3/omega-6 free fatty acids or elimination of artificial food colorings, effects that were small or restricted to food-sensitive individuals.
ObjectiveNonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments.MethodUsing a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome.ResultsFifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21–0.48) and psychological (standardized mean differences=0.40–0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments.ConclusionsFree fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.
Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in
(HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among ...HP-infected subjects who had received HP therapy.
This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure.
Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years.
Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.
Background
The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and ...its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience.
Methods
We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2–12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent–child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic.
Results
The study included 29,202 individual families; of which 12,163 had children aged 2–5 years and 17,029 had children aged 6–12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers.
Conclusions
This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.
Although eradication of Helicobacter pylori infection reduces the risk of gastric cancer, few data are available on its effects in older subjects. We compared the age-specific risk of gastric cancer ...in a large cohort of subjects who received H pylori eradication therapy vs a matched general population.
We searched the Hospital Authority database of Hong Kong to identify individuals with H pylori infection who had received a course of clarithromycin-containing eradication therapy from January 2003 through December 2012. We compared the gastric cancer incidence in this cohort with the expected incidence for the local general population by retrieving the gastric cancer incidence of the age- and sex-matched population from 2003 through 2014 (the latest available year) from the Hong Kong Cancer Registry. The primary outcome was the incidence of gastric cancer development in the cohort treated for H pylori infection vs the expected number of gastric cancer cases in the general population. Analyses were conducted by a priori age groups of less than 40 years, 40–59 years, and 60 years or older.
Among 73,237 subjects infected with H pylori who received eradication therapy, 200 (0.27%) developed gastric cancer during a median follow-up time of 7.6 years. Compared with the matched general population, the gastric cancer risk was significantly lower in subjects 60 years or older who had received H pylori treatment (standardized incidence ratio SIR, 0.82; 95% confidence interval CI, 0.69–0.97; P = .02) but not in younger groups. When data were stratified based on time from H pylori treatment (less than 5 years, 5–9 years, and 10 or more years), the risk of gastric cancer was significantly lower than the general population 10 or more years after eradication in the group 40–59 years old (SIR 0.32; 95% CI, 0.08–0.88; P = .04) and the group 60 years or older (SIR, 0.42; 95% CI, 0.42–0.84; P = .02) than the other age groups.
In an analysis of data from a public hospital database on Hong Kong, we associated treatment of H pylori infection with a lower risk of gastric cancer, particularly in older subjects, 10 or more years after treatment.
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IMPORTANCE: The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. OBJECTIVE: To investigate the risk of osteoporotic fracture with ...dabigatran vs warfarin in patients with NVAF. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. EXPOSURES: Dabigatran or warfarin use during the study period. MAIN OUTCOMES AND MEASURES: Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. RESULTS: Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean SD age, 74 11 years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users 1.0%; 72 warfarin users 1.5%). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, −0.68 95% CI, −0.38 to −0.86; IRR, 0.38 95% CI, 0.22 to 0.66). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, −3.15 95% CI, −2.40 to −3.45; IRR, 0.12 95% CI, 0.04 to 0.33), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, −0.04 95% CI, 0.67 to −0.39; IRR, 0.95 95% CI, 0.45 to 1.96) (P value for interaction, <.001). CONCLUSIONS AND RELEVANCE: Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.
The 2017 WHO Model List of Essential Medicines for Children (EMLc) groups antibiotics as Access, Watch, or Reserve, based on recommendations of their use as first-choice and second-choice empirical ...treatment for the most common infections. This grouping provides an opportunity to review country-level antibiotic consumption and a potential for stewardship. Therefore, we aimed to review 2015 levels of oral antibiotic consumption by young children globally.
We analysed wholesale antibiotic sales in 70 middle-income and high-income countries in 2015. We identified oral antibiotic formulations appropriate for use in young children (defined as child-appropriate formulations CAFs) using wholesale data from the IQVIA-Multinational Integrated Data Analysis System database, and we estimated 2015 antibiotic consumption in reference to the 2017 WHO EMLc Access, Watch, Reserve (AWaRe) antibiotic groups. We used three metrics for assessment of intra-country patterns: access percentage, defined as the number of CAF standard units of Access antibiotics divided by the total number of CAF standard units; amoxicillin index, defined as the number of amoxicillin CAF standard units divided by the total number of CAF standard units; and access-to-watch index, defined as the ratio of Access-to-Watch CAF standard units.
The overall median volume of CAF antibiotic standard units sold in 2015 per country was 74·5 million (IQR 12·4–210·7 million). The median access percentage among the 70 countries was 76·3% (IQR 62·6–84·2). The amoxicillin index was low (median 30·7%, IQR 14·3–47·3). The median access-to-watch index was 6·0 (IQR 3·1–9·8). CAF antibiotic consumption patterns were highly variable between the 70 countries, without a clear difference between high-income and middle-income countries.
Antibiotics in the Access group have a key role in treating young children globally. A simple combination of metrics based on the AWaRe groups can be informative on individual countries' patterns of antibiotic consumption and stewardship opportunities. These metrics could support countries in the development of programmes to improve access to core Access antibiotics, particularly amoxicillin.
Global Antibiotic R&D Partnership (German Federal Ministry of Health, Médecins Sans Frontières, Netherlands Ministry of Health, Welfare and Sport, and UK Department for International Development).
Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterised by the symptoms of inattention, impulsivity and hyperactivity. ADHD was once perceived as a ...condition of childhood only; however increasing evidence has highlighted the existence of ADHD in older adolescents and adults. Estimates for the prevalence of ADHD in adults range from 2.5-4%. Few data exist on the prescribing trends of the stimulants methylphenidate and dexamfetamine, and the non-stimulant atomoxetine in the UK. The aim of this study was to investigate the annual prevalence and incidence of pharmacologically treated ADHD in children, adolescents and adults in UK primary care.
The Health Improvement Network (THIN) database was used to identify all patients aged over 6 years with a diagnosis of ADHD/hyperkinetic disorder and a prescription for methylphenidate, dexamfetamine or atomoxetine from 2003-2008. Annual prevalence and incidence of pharmacologically treated ADHD were calculated by age category and sex.
The source population comprised 3,529,615 patients (48.9% male). A total of 118,929 prescriptions were recorded for the 4,530 patients in the pharmacologically treated ADHD cohort during the 6-year study. Prevalence (per 1000 persons in the mid-year THIN population) increased within each age category from 2003 to 2008 6-12 years: from 4.8 (95% CI: 4.5-5.1) to 9.2 (95% CI: 8.8-9.6); 13-17 years: from 3.6 (95% CI: 3.3-3.9) to 7.4 (95% CI: 7.0-7.8); 18-24 years: from 0.3 (95% CI: 0.2-0.3) to 1.1 (95% CI: 1.0-1.3); 25-45 years: from 0.02 (95% CI: 0.01-0.03) to 0.08 (95% CI: 0.06-0.10); >45 years: from 0.01 (95% CI: 0.00-0.01) to 0.02 (95% CI: 0.01-0.03). Whilst male patients aged 6-12 years had the highest prevalence; the relative increase in prescribing was higher amongst female patients of the same age - the increase in prevalence in females aged 6-12 years was 2.1 fold compared to an increase of 1.9 fold for their male counterparts. Prevalence of treated ADHD decreased with increasing age. Incidence (per 1000 persons at risk in the mid-year THIN population) was highest for children aged 6-12 years.
A trend of increasing prescribing prevalence of ADHD drug treatment was observed over the period 2003-2008. Prevalence of prescribing to adult patients increased; however the numbers treated are much lower than published estimates of the prevalence of ADHD. This study has added to the limited knowledge on ADHD prescribing in primary care, particularly in the area of drug treatment in adulthood.
Rationale
Previous studies on psychotropic drugs prescribing in autism spectrum disorder (ASD) were from the USA or the UK. However, these studies may not be generalizable to other countries. There ...is a need to understand the extent of psychopharmacological prescribing for ASD treatment at a multinational level to identify areas of prescribing which lack evidence.
Methods
We used the IMS Prescribing Insights database to investigate psychotropic drugs prescribing patterns for ASD treatment in children and adults in 2010–2012. Data were obtained from Europe (France, Germany, Italy, Spain and UK), South America (Mexico and Brazil), North America (Canada and USA) and Asia (Japan).
Results
North American countries have the highest prescription rates, followed by the European and South American countries. Prescribing rates were higher in children compared to adults in individual countries. The most commonly prescribed drug for ASD was risperidone in young people (except in UK and Japan). In the UK, methylphenidate (34 %) was the most commonly prescribed for young people and haloperidol (44.1 %) in Japan. In adults, the most commonly prescribed drug class was antipsychotics and particularly risperidone (thioridazine and ziprasidone were the most prescribed antipsychotics in Brazil and USA, respectively).
Conclusion
There is variation in medication prescription for people with ASD among countries, which may be attributable to diagnostic criteria, clinical guidelines or health care systems. However, there is a lack of evidence of efficacy and safety for many psychotropic drugs prescribed for people with ASD. Research is needed to bridge the evidence gaps in prescribing.
Background
Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with ...cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.
Objectives
To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.
Methods
We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0–18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.
Results
Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4–96 weeks). All three medications were associated with a small, but statistically significant pre–post increase of SBP (MPH: standard mean difference SMD 0.25, 95% confidence interval CI 0.08–0.42,
p
< 0.01; AMP: SMD 0.09, 95% CI 0.03–0.15,
p
< 0.01; ATX: SMD 0.16, 95% CI 0.04–0.27,
p
= 0.01). MPH did not have a pre–post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre–post increase of DBP (SMD 0.16, CI 0.03–0.29,
p
= 0.02), as was ATX treatment (SMD 0.22, CI 0.10–0.34,
p
< 0.01). AMP and ATX were associated with a small to medium statistically significant pre–post increase of HR (AMP: SMD 0.37, CI 0.13–0.60,
p
< 0.01; ATX: SMD 0.43, CI 0.26–0.60,
p
< 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (
F
(1) = 19.55,
p
= 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (
F
(1) = 5.346,
p
= 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.
Conclusions
Statistically significant pre–post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.
Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are prone to sustaining trauma that requires emergency department (ED) admission. Methylphenidate (MPH) can reduce ADHD ...symptoms and may thus theoretically reduce the risk of trauma-related ED admission, but previous studies do not make this association clear. This study examines this association.
A total of 17 381 patients aged 6 to 19 years who received MPH prescriptions were identified by using the Clinical Data Analysis & Reporting System (2001-2013). Using a self-controlled case series study design, the relative incidence of trauma-related ED admissions was compared with periods of patient exposure and nonexposure to MPH.
Among 17 381 patients prescribed MPH, 4934 had at least 1 trauma-related ED admission. The rate of trauma-related ED admission was lower during exposed periods compared with nonexposed periods (incidence rate ratio IRR: 0.91 95% confidence interval (CI): 0.86-0.97). The findings were similar only when the incident trauma episode was assessed (IRR: 0.89 95% CI: 0.82-0.96). A similar protective association was found in both genders. In validation analysis using nontrauma-related ED admissions as a negative control outcome, no statistically significant association was found (IRR: 0.99 95% CI: 0.95-1.02). All sensitivity analyses demonstrated consistent results.
This study supports the hypothesis that MPH is associated with a reduced risk of trauma-related ED admission in children and adolescents. A similar protective association was found in both male and female patients. This protective association should be considered in clinical practice.
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