Layperson-Led vs Professional-Led Behavioral Interventions for Weight Loss in Pediatric Obesity: A Systematic Review and Meta-analysis.

Importance: The appropriate approach for weight loss among children and adolescents with overweight and obesity remains unclear. Objective: To evaluate the difference in the treatment outcomes associated with behavioral weight loss interventions led by laypersons and professionals in comparison with unsupervised control arms among children and adolescents with overweight and obesity. Data Sources: For this systematic review and meta-analysis, the Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, the Cochrane Library, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases were searched from January 1, 1996, to June 1, 2019. Study Selection: Included in this study were randomized clinical trials (RCTs) of behavioral interventions lasting at least 12 weeks for children and adolescents (aged 5-18 years) with overweight and obesity. Exclusion criteria included non-RCT studies, interventions lasting less than 12 weeks, adult enrollment, participants with other medical diagnoses, pharmacological treatment use, and articles not written in English. Two of 6 reviewers independently screened all citations. Of 25 586 citations, after duplicate removal, 78 RCTs (5780 participants) met eligibility criteria. Data Extraction and Synthesis: A bayesian framework and Markov chain Monte Carlo simulation methods were used to combine direct and indirect associations. Random-effects and fixed-effect network meta-analysis models were used with the preferred model chosen by comparing the deviance information criteria. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The immediate and sustained changes in weight and body mass index (BMI) standardized mean difference (SMD) were primary outcomes planned before data collection began, whereas waist circumference and percent body fat were secondary outcomes. The hypothesis being tested was formulated before the data collection. Results: Of 25 586 citations retrieved, we included 78 RCTs (5780 participants), with a follow-up of 12 to 104 weeks. Compared with the control condition, random-effects models revealed that professional-led weight loss interventions were associated with reductions in weight (mean difference [MD], -1.60 kg [95% CI, -2.30 to -0.99 kg]; 68 trials; P < .001) and BMI (SMD, -0.30 [95% CI, -0.39 to -0.20]; 59 trials; P < .001) that were not sustained long term (weight MD, -1.02 kg [95% CI, -2.20 to 0.34 kg]; 21 trials; P = .06; BMI SMD, -0.12 [95% CI, -0.46 to 0.21]; 20 trials; P < .001). There was no association between layperson-led interventions and weight loss in the short-term (MD, -1.40 kg [95% CI, -3.00 to 0.26 kg]; 5 trials; P = .05) or long-term (MD, -0.98 kg [95% CI, -3.60 to 1.80 kg]; 1 trial; P = .23) compared with standard care. No difference was found in head-to-head trials (professional vs layperson MD, -0.25 kg [95% CI -1.90 to 1.30 kg]; 5 trials; P = .38). Conclusions and Relevance: This systematic review and meta-analysis found that professional-led weight loss interventions were associated with short-term but not sustained weight reduction among children and adolescents with overweight or obesity, and the evidence for layperson-led approaches was insufficient to draw firm conclusions.

Vitamins and Minerals for Migraine Prophylaxis: A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. METHODS: We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. RESULTS: Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) -0.44 (-2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD -1.97 (-4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) -0.05 (-0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM -0.17 (-0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. CONCLUSIONS: Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.

Long-term trends in invasive pneumococcal disease in Manitoba, Canada.

Invasive pneumococcal disease (IPD) remains a significant public health problem in Manitoba, Canada although publically-funded pneumococcal conjugate (PCV7 and PCV13) and polysaccharide (PPV23) vaccination programs exist. We analyzed routine surveillance and administrative health data to examine trends in IPD rates as these vaccines were introduced. Data on all individuals with a laboratory-confirmed diagnosis of IPD between 2001 and 2014 were obtained from the provincial Communicable Diseases Surveillance database and linked with Manitoba's provincial immunization registry and physician and hospital databases. We calculated IPD incidence rates overall, by serotype and for different population subgroups defined by socio-demographic and clinical (e.g., chronic diseases, immune status) characteristics. Annual IPD incidence (95%CI) was 8.6 (8.2-9.1)/100,000 people during the study period (n = 1092), and rates were higher in recent years and in regions with predominately indigenous populations. Reduction in the incidence of serotypes included in PCV7 have been offset by rising rates of PCV13-only serotypes in children, and more recently by rising rates of PPV-only serotypes and non-vaccine serotypes among young children and older adults (≥ 65 years). Rates were 3 times higher in those with a chronic disease and highest (> 175-fold) among alcoholics, organ-transplant, and chronic kidney failure patients. The case fatality rate was 12.0% within 30 d of diagnosis. Despite the introduction of several vaccination programs, overall rates of IPD have not declined in Manitoba in the last decade, due to increase in incidence of non-PCV7 serotypes. A disproportionately high burden of disease impacts indigenous communities and people with chronic disease.

Evolution and molecular characterization of macrolide-resistant Streptococcus pneumoniae in Canada between 1998 and 2008.

OBJECTIVES: Studies were performed to assess resistance mechanisms, multidrug resistance (MDR), genetic relatedness, serotype distribution, heptavalent pneumococcal conjugate vaccine (PCV7) coverage and pili virulence factors among macrolide-resistant Streptococcus pneumoniae (MRSP) isolated from respiratory samples submitted to hospital laboratories across Canada from 1998 to 2008. METHODS: Isolates of MRSP (n = 1518) collected by the national surveillance studies CROSS (Canadian Respiratory Organism Susceptibility Study; 1998-2006) and CANWARD (Canadian Ward Surveillance Study; 2007-08) were tested using the CLSI broth microdilution method to establish antimicrobial susceptibilities. PCR was used to detect macrolide resistance genes [mef(A) and erm(B)] and pili virulence factors (type 1 pili and type 2 pili), the Quellung reaction was used to identify serotypes and PFGE was used to determine genetic relatedness. RESULTS: The prevalence of MRSP increased from 8% in 1998 to 22% in 2008 (P = 0.0001). MRSP were 51% mef(A) positive, 36% erm(B) positive, 8% dual mef(A) and erm(B) positive and 5% mef(A) and erm(B) negative. Dual mef(A)- and erm(B)-positive isolates increased in prevalence from 3% in 1998 to 19% in 2008 (P = 0.001). The prevalence of PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) decreased from 67% in 1998 to 31% in 2008 (P = 0.0072). The prevalence of serotype 19A, a non-PCV7 serotype, increased by 15% from 1998 to 2008; isolates of serotype 19A were MDR, dual mef(A) and erm(B) positive, genetically related by PFGE and associated with the presence of pili virulence factors. CONCLUSIONS: From 1998 to 2008, respiratory isolates of MRSP in Canada increased significantly due primarily to the emergence and spread of serotypes 6A, 19A and other non-PCV7 serotypes.

Molecular characterisation of Canadian paediatric multidrug-resistant Streptococcus pneumoniae from 1998-2004.

Multidrug-resistant (MDR) Streptococcus pneumoniae (i.e. resistant to three different antimicrobial classes) is a global concern. The molecular epidemiology of MDR S. pneumoniae has not been characterised in Canadian paediatric isolates. Paediatric MDR S. pneumoniae were obtained from a national surveillance study. Susceptibility testing was performed by the methods of the Clinical and Laboratory Standards Institute. Phenotypic and genotypic relatedness were assessed by serotyping and pulsed-field gel electrophoresis (PFGE). Penicillin resistance was assessed with polymerase chain reaction (PCR) followed by DNA sequencing of penicillin-binding proteins (PBPs) 1A, 2B and 2X. Macrolide resistance was assessed by PCR-based detection of mef(E) and erm(B). PCR and sequencing of the dihydrofolate reductase (DHFR) gene was performed to assess resistance to trimethoprim/sulphamethoxazole (T/S). Seventy (98.6%) of 71 MDR paediatric isolates were concomitantly resistant to penicillin, erythromycin and T/S. Resistance genes mef(E) (66.2%) or erm(B) (22.5%) or both mef(E) and erm(B) (8.5%) were associated with macrolide resistance, and the prevalence of erm(B) increased significantly (P=0.0001) over time. Penicillin resistance was associated with amino acid substitutions in PBPs 1A, 2B and 2X. Resistance to T/S was associated with amino acid substitutions in the DHFR gene; in particular, Ile100-->Leu was detected in all isolates analysed. PFGE revealed three clusters of isolates that were genetically related and associated with specific serotypes (Taiwan(19F), Spain(23F), Spain(14) and France(9V)), suggesting clonal expansion as the primary means of paediatric MDR S. pneumoniae dissemination in Canada. The heptavalent pneumococcal vaccine Prevnar, currently approved in Canada for use in children < or =2 years of age, provided excellent coverage (90.2%) of paediatric MDR S. pneumoniae. In conclusion, paediatric MDR S. pneumoniae simultaneously resistant to penicillin, erythromycin and T/S are genetically similar and disseminating across Canada. Prevnar provides excellent coverage of paediatric MDR S. pneumoniae.

The use of macrolides in treatment of upper respiratory tract infections.

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to beta-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found to be responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species, producing an efflux pump (mef), and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.

Expression of the mef(E) gene encoding the macrolide efflux pump protein increases in Streptococcus pneumoniae with increasing resistance to macrolides.

Active macrolide efflux is a major mechanism of macrolide resistance in Streptococcus pneumoniae in many parts of the world, especially North America. In Canada, this active macrolide efflux in S. pneumoniae is predominantly due to acquisition of the mef(E) gene. In the present study, we assessed the mef(E) gene sequence as well as mef(E) expression in variety of low- and high-level macrolide-resistant, clindamycin-susceptible (M-phenotype) S. pneumoniae isolates (erythromycin MICs, 1 to 32 microg/ml; clindamycin MICs, < or = 0.25 microg/ml). Southern blot hybridization with mef(E) probe and EcoRI digestion and relative real-time reverse transcription-PCR were performed to study the mef(E) gene copy number and expression. Induction of mef(E) expression was analyzed by Etest susceptibility testing pre- and postincubation with subinhibitory concentrations of erythromycin, clarithromycin, azithromycin, telithromycin, and clindamycin. The macrolide efflux gene, mef(E), was shown to be a single-copy gene in all 23 clinical S. pneumoniae isolates tested, and expression post-macrolide induction increased 4-, 6-, 20-, and 200-fold in isolates with increasing macrolide resistance (erythromycin MICs 2, 4, 8, and 32 microg/ml, respectively). Sequencing analysis of the macrolide efflux genetic assembly (mega) revealed that mef(E) had a 16-bp deletion 153 bp upstream of the putative start codon in all 23 isolates. A 119-bp intergenic region between mef(E) and mel was sequenced, and a 99-bp deletion was found in 11 of the 23 M-phenotype S. pneumoniae isolates compared to the published mega sequence. However, the mef(E) gene was fully conserved among both high- and low-level macrolide-resistant isolates. In conclusion, increased expression of mef(E) is associated with higher levels of macrolide resistance in macrolide-resistant S. pneumoniae.

The Use of Macrolides in Treatment of Upper Respiratory Tract Infections.

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to b-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species producing an efflux pump (mef) and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.

Molecular epidemiology and prevalence of macrolide efflux genes mef(A) and mef(E) in Streptococcus pneumoniae obtained in Canada from 1997 to 2002.

One hundred forty M phenotype Streptococcus pneumoniae isolates were evaluated by PCR-restriction fragment length polymorphism, serotyping, and pulsed-field gel electrophoresis. Molecular genotyping revealed that the predominant macrolide resistance mechanism in S. pneumoniae in Canada is mef(E) and resistance dissemination is due to both spread of the genetic element MEGA as well as clonal dissemination of penicillin- and/or macrolide-resistant strains.

The Use of Ketolides in Treatment of Upper Respiratory Tract Infections.

Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs. The ketolides, of which telithromycin is the first to be available for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides possess innovative structural modifications, a 3-keto group and a large N-substituted C11, C12-carbamate side chain. This novel structure allows ketolides, which are inhibitors of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to macrolide-lincosamide-streptogramin B-resistant ribosomes. This novel chemical structure also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric fluid and at cellular/tissue levels. Early clinical trials support the bacteriologic and clinical efficacy of telithromycin in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including infections caused by macrolide-resistant S. pneumoniae and S. pyogenes. Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate severity, and rarely involve withdrawal of the drug. Telithromycin represents an attractive option for the empiric treatment of upper RTIs, especially as resistance to macrolides is likely to continue to increase.