Efficacy and Safety of Interferon-Gamma in Chronic Granulomatous Disease: a Systematic Review and Meta-analysis.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency with increased susceptibility to several bacteria, fungi, and mycobacteria, caused by defective or null superoxide production by the NADPH oxidase enzymatic complex. Accepted treatment consists mainly of antimicrobial prophylaxis. The role of human recombinant subcutaneous interferon-gamma (IFNγ) is less clear since the available evidence on its efficacy derives mainly from a single clinical trial that has been challenged. OBJECTIVE: We aimed to assess the efficacy and safety of IFNγ as an added treatment for CGD when compared to antimicrobial prophylaxis alone. METHODS: A literature search was conducted using MeSH terms "Chronic granulomatous disease" AND ("interferon gamma" OR "interferon-gamma"), as well as antibiotics, placebo, no therapy, clinical trial, and trial, on MEDLINE, EMBASE, LILACS, WHOs, CENTRAL, KOREAMED, The Cochrane Library, clinicaltrials.gov, and abstracts from meetings, from 1976 to July 2022. We included clinical trials (CT) and prospective follow-up studies and registered the number of serious infections (requiring hospitalization and IV antibiotics) and deaths, adverse events, and autoimmune complications, in patients treated for CGD with antimicrobial prophylaxis plus IFN-γ, versus antimicrobial prophylaxis alone. We assessed the quality of the studies using risk of bias and STROBE. We performed a meta-analysis by calculating both Peto's odds ratio (OR) and risk reduction (RR) through the Mantel-Haenszel method with a fixed-effect model, using Review Manager 5.4, and we reported the number needed to treat (NNT). RESULTS: We identified 54 matches from databases and 4 from other sources. We excluded 12 duplicates, 7 titles, and 9 abstracts for relevance, after which we had 30 eligible studies. Twenty-four were then excluded after reading the full text. Six papers were included: one randomized CT and 5 follow-up studies. In total, 324 patients with Chronic granulomatous disease were followed for 319 months under treatment with antibiotic prophylaxis plus interferon-gamma or placebo (or antibiotic prophylaxis alone), reported between the years 1991 and 2016. Three of the studies included a control group, allowing for the aggregate analysis of efficacy (prevention of serious infections). The aggregate OR was 0.49, with a 95% confidence interval of 0.19 to 1.23. The risk ratio for serious infection was 0.56 (95%CI 0.35-0.90) under IFN-γ. The meta-analysis thus favors interferon-gamma for a risk reduction of serious infection. DISCUSSION: The results from this meta-analysis support the use of IFN-γ in the treatment of patients with CGD. However, we found insufficient clinical evidence and believe more clinical trials are needed to better assess the efficacy and long-term safety of IFN-γ.

IgA vasculitis (Henoch - Schönlein Purpura) as the first manifestation of juvenile Systemic Lupus Erythematosus: Case-control study and systematic review.

BACKGROUND: We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature. AIM: To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE. METHODS: A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects. RESULTS: The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively. CONCLUSION: IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.

Ambroxol for women at risk of preterm birth for preventing neonatal respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant (an active agent that keeps pulmonary alveoli open and facilitates the entry of air to the lungs, thus improving the oxygenation of the newborn).A number of interventions such as pulmonary surfactant and prenatal corticosteroids are used to prevent RDS. Ambroxol has been studied as a potential agent to prevent RDS, but effectiveness and safety has yet to be evaluated. OBJECTIVES: To evaluate the efficacy and safety of giving ambroxol to pregnant women who are at risk of preterm birth, for preventing neonatal RDS. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 November 2013), CENTRAL (The Cochrane Library 2013, Issue 11),Embase (1988 to November 2013), MEDLINE (PubMed 1970 to November 2013), LILACS (1982 to November 2013), the WHO International Clinical Trials Registry Platform (ICTRP) (November 2013) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the administration of ambroxol given to pregnant women at risk of preterm birth versus placebo, antenatal corticosteroids (betamethasone or dexamethasone), or no treatment.We did not identify any trials comparing ambroxol with dexamethasone (corticosteroid) in this review. Nor did we identify any trials comparing ambroxol combined with corticosteroid versus corticosteroid alone, or placebo/no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We included 14 studies (in 18 trial reports), involving 1047 pregnant women at risk of preterm birth with 1077 newborns. However, three of the included studies did not report on this review's outcomes of interest. We carried out two main comparisons: ambroxol versus antenatal corticosteroids (betamethasone); and ambroxol versus placebo or no treatment. Seven RCTs provided data for our comparison of ambroxol versus corticosteroid (betamethasone) and two trials contributed data to our comparison of ambroxol compared to placebo or no treatment.The included studies were generally judged as having either 'low' risk of bias or 'unclear' risk of bias (because the trial reports provided insufficient details about methods of sequence generation, allocation concealment and blinding). Primary outcomesThere was no clear evidence of a difference in the incidence of RDS among newborns born to women who received ambroxol when compared to newborns of women who were given the corticosteroid, betamethasone (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07, seven RCTs, 728 women/758 newborns, moderate quality evidence) or placebo/no treatment (average RR 0.74; 95% CI 0.46 to 1.20, two studies, 204 women/204 newborns,T2= 0.07; I(2)= 53%, low-quality evidence). Results were imprecise and consistent with appreciable benefit as well as negligible effect.Similarly, there was no clear evidence of a difference in the rates of perinatal mortality between the group of women who received ambroxol and women in the corticosteroid (betamethasone) group (RR 0.51, 95% CI 0.23 to 1.12, six studies, 648 women/657 newborns, moderate quality evidence) or the placebo/no treatment group (RR 0.61; 95% CI 0.19 to 1.98, one study, 116 women/116 newborns, low-quality evidence).In terms of maternal adverse effects, there was no clear differences (in nausea or vomiting) between those women who received ambroxol compared to either those women who received corticosteroids (betamethasone) (average RR 3.45; 95% CI 0.34 to 35.51, three studies, 305 women, T(2)= 2.82; I(2)= 67%, very low-quality evidence), or women who received placebo or no treatment (RR 1.79; 95% CI 0.45 to 7.13, one study, 116 women, low-quality evidence). No other adverse effects (e.g. diarrhoea, gastric irritation and headache) were reported in the included studies. Secondary outcomesFor the review's secondary outcomes, none of the included studies reported on the incidence of bronchopulmonary dysplasia, periventricular haemorrhage, necrotising enterocolitis or rate of maternal mortality.One small trial (involving 88 women) comparing ambroxol with placebo or no treatment, reported no difference between groups in terms of the need for mechanical ventilation in the neonate (RR 0.94; 95% CI 0.73 to 1.21, 88 women/88 babies, low-quality evidence) or the administration of pulmonary surfactant (RR 1.19; 95% CI 0.61 to 2.30, one RCT, 88 women/88 babies, low-quality evidence). AUTHORS' CONCLUSIONS: This review is based on very low to moderate quality evidence from 14 small trials (many are published in the form of conference abstracts with minimal methodological details provided). There is insufficient evidence to support or refute the practice of giving ambroxol to women at risk of preterm birth for preventing neonatal RDS, perinatal mortality and adverse effects. More research is needed in order to fully evaluate the benefits and risks of this intervention.

Bone mineral density after bariatric surgery. A systematic review.

PURPOSE: Bone regulation system may be affected after bariatric surgeries, but procedures impact differently to bone mineral density (BMD) and measures restraining bone loss are frequently neglected until clinical consequences become manifest. This is a systematic review aimed to elucidate whether BMD loss is comparable after different bariatric surgeries. MATERIALS AND METHODS: A search of morbid obese adults, undergone to bariatric surgery, with BMD measured by dual-energy X-ray absorptiometry at baseline and after surgery studies was performed in several databases. Studies were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and COCHRANE Risk of Bias tool. The random model was selected for meta-analysis; heterogeneity was analyzed with T(2), inconsistency (I(2) > 50%) and Chi(2) (p < 0.10). Level of evidence and strength of recommendations were summarized using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE System). RESULTS: Twelve studies met the selection criteria. After one year, reduction in total BMD in patients with mixed surgical procedures was significant: -0.03 g/cm(2) (CI 95% 0.00 to -0.06, p < 0.05). BMD was reduced by -0.12 g/cm(2) (CI 95% -0.10 to -0.15, p < 0.001) in the hip, -0.07 g/cm(2) (CI 95% -0.03 to -0.11, p < 0.001) in the column, and -0.03 g/cm(2) (IC 95% -0.02 to -0.04, p < 0.001) in the forearm, but not in restrictive surgeries. Studies included showed high heterogeneity and low quality of evidence. CONCLUSIONS: Patients undergone to mixed bariatric surgery had significant higher BMD deterioration as demonstrated in this review, suggesting that more attention for preventing fractures is required.

[ARIA Mexico 2014. Adaptation of the Clinical Practice Guide ARIA 2010 for Mexico. Methodology ADAPTE]. / ARIA México 2014. Adaptación de la Guía de Práctica Clínica ARIA 2010 para México. Metodología ADAPTE.

BACKGROUND: The global prevalence of allergic rhinitis is high. International Study of Asthma and Allergies in Childhood (ISAAC) Phase III reports a total estimated prevalence of 4.6% in Mexico. There is evidence based on allergic rhinitis Clinical Practice Guidelines (CPG), but its promotion, acceptance and application is not optimal or adequate in Mexico. OBJECTIVE: To generate a guideline for the treatment of allergic rhinitis and its impact on asthma by adaptating the 2010 ARIA Guideline to Mexican reality, through a transculturation process applying the ADAPTE methodology. PATIENTS AND METHOD: Using the ADAPTE Methodology, the original 2010 ARIA CPG recommendations were evaluated by the guideline development group (GDG) into which multiple medical specialities managing patients with allergic rhinitis were incoorporated. The GDG valorated the quality of 2010 ARIA, checked and translated key clinical questions. Moreover, the GDG adjusted recommendations, patient preferences and included comments in the context of the Mexican reality (safety, costs and cultural issues). To accomplish this, we ran Delphi panels with as many rounds as necessary to reach agreement. One extra question, not included in the original 2010 ARIA, on the use of Nasal Lavages for AR was created sustained by a systematic literature review. RESULTS: A total of 45 questions from the original 2010 ARIA were included and divided into six groups covering prevention, medical treatment, immunotherapy and alternative medicine to treat patients with allergic rhinitis with or without asthma. Most of the questions reached agreement in one or two rounds; one question required three rounds. CONCLUSIONS: An easy-to-use, adaptated, up-to-date and applicable allergic rhinitis guideline for Mexico is now available.

ANTECEDENTES: la prevalencia de rinitis alérgica en todo el mundo es alta. El Estudio Internacional de Asma y Alergias en la Niñez (ISAAC de International Study of Asthma and Allergies in Childhood) Fase III reporta una prevalencia estimada total en México de 4.6%. Existen guías de práctica clínica basadas en evidencia de rinitis alérgica, pero su promoción, aceptación y validez no son óptimas ni adecuadas para México. OBJETIVO: generar una guía de tratamiento de la rinitis alérgica y su repercusión en el asma adaptando la guía ARIA 2010 a la realidad mexicana mediante un proceso de transculturización, por medio de la metodología ADAPTE. MATERIAL Y MÉTODO: a través de la metodología ADAPTE un grupo de desarrollo de la guía, integrado por múltiples especialistas que tratan pacientes con rinitis alérgica, valoró la calidad de la guía ARIA 2010, revisó y tradujo las preguntas clínicas clave y ajustó las recomendaciones, preferencias del paciente y comentarios a la realidad mexicana (seguridad, costos y aspectos culturales). Para lograrlo se corrieron páneles Delphi, con tantas rondas como fuera necesario hasta lograr un acuerdo. Por medio de una revisión sistemática de la bibliografía se creó una pregunta especial no incluida en ARIA 2010 de la utilidad de realizar lavados nasales en pacientes con rinitis alérgica. RESULTADOS: se incluyeron 45 preguntas de la guía original ARIA 2010, divididas en seis bloques que abarcan prevención, tratamiento médico, inmunoterapia y terapias alternativas de pacientes con rinitis alérgica con o sin asma. La mayor parte de las preguntas alcanzaron acuerdo en una a dos rondas, sólo una requirió tres para ello. CONCLUSIONES: se cuenta ahora con una guía de rinitis alérgica de usosencillo, adaptada, actualizada y válida para México.