Monoclonal antibody therapies in respiratory syncytial virus prophylaxis-An umbrella review.

The aim was to gather an overview of the evidence of monoclonal antibody therapies in respiratory syncytial virus (RSV) prophylaxis in children. For this umbrella review of previous meta-analyses, we searched PubMed, Scopus, and Web of Science databases in August 2023. We included systematic reviews with meta-analyses of randomized controlled trials. One author extracted the data, and another author validated the data. We extracted all analyses focusing on clinical outcomes and comparing prophylaxis to placebo. Risk of bias in systematic reviews (ROBIS) tool was used to analyze the risk of bias in the included reviews. AMSTAR-2 was used to evaluate the quality of the included reviews. After screening of 323 abstracts and 22 full reports, a total of seven systematic reviews with meta-analyses were included. The risk of bias was rated to be low in four and high in three of these. Three reviews were of moderate quality, one low, and three very low quality according to AMSTAR-2 classification. Six of the meta-analyses were direct comparisons, and one was a network meta-analysis. Five of the reviews focused on palivizumab, one in nirsevimab, and one included all monoclonal antibodies. Six reviews focused on preterm neonates and consisted of 42 comparisons to placebo of which 21 showed efficacy, and 21 had no evidence of a difference. The positive effect was seen in all reviews against RSV infection and RSV hospitalization in palivizumab and nirsevimab groups compared to placebo. None of the mortality comparisons showed efficacy. One meta-analysis focused on cystic fibrosis patients and had eight comparisons, but it was underpowered to detect any results. The overall evidence from previous meta-analyses shows that monoclonal antibodies are effective in preventing RSV infections and RSV hospitalizations in preterm infants. However, no effect on mortality was seen in these studies. Evidence certainty has been ranked mainly from low to moderate.

Impact of childhood traumatic brain injury on fitness for service class, length of service period, and cognitive performance during military service in Finland from 1998 to 2018: A retrospective register-based nationwide cohort study.

INTRODUCTION: Traumatic brain injury (TBI) can cause neuronal damage and cerebrovascular dysfunction, leading to acute brain dysfunction and considerable physical and mental impairment long after initial injury. Our goal was to assess the impact of pediatric TBI (pTBI) on military service, completed by 65-70% of men in Finland. METHODS: We conducted a retrospective register-based nationwide cohort study. All patients aged 0 to 17 years at the time of TBI, between 1998 and 2018, were included. Operatively and conservatively treated patients with pTBI were analyzed separately. The reference group was comprised of individuals with upper and lower extremity fractures. Information on length of service time, service completion, fitness for service class, and cognitive performance in a basic cognitive test (b-test) was gathered from the Finnish Military Records for both groups. Linear and logistic regression with 95% CI were used in comparisons. RESULTS: Our study group comprised 12 281 patients with pTBI and 20 338 reference group patients who participated in conscription. A total of 8 507 (66.5%) men in the pTBI group and 14 953 (71.2%) men in the reference group completed military service during the follow-up period. Men in the reference group were more likely to complete military service (OR 1.26, CI 1.18-1.34). A total of 31 (23.3%) men with operatively treated pTBI completed the military service. Men with conservatively treated pTBI had a much higher service rate (OR 7.20, CI 4.73-11.1). In the pTBI group, men (OR 1.26, CI 1.18-1.34) and women (OR 2.05, CI 1.27-3.36) were more likely to interrupt military service than the reference group. The PTBI group scored 0.15 points (CI 0.10-0.20) less than the reference group in cognitive b-test. CONCLUSIONS: PTBI groups had slightly shorter military service periods and higher interruption rate than our reference-group. There were only minor differences between groups in cognitive b-test.

Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) reduces extubation failures in preterm neonates-A systematic review and meta-analysis.

AIM: To analyse the evidence of non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in preterm neonates compared to nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV). METHODS: We performed a systematic review and meta-analysis of randomised controlled trials and included studies where NIV-NAVA was analysed in preterm (<37 gestational weeks) born neonates. Our main outcomes were the need for endotracheal intubation, the need for surfactant therapy, and reintubation rates. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of five studies were included. The endotracheal intubation rate was 25% in the NIV-NAVA group and 26% in the nCPAP group (RR 0.91, CI: 0.56-1.48). The respective rates for surfactant therapy were 30% and 35% (RR 0.85, CI: 0.56-1.29). The reintubation rate in neonates previously invasively ventilated was 8% in the NIV-NAVA group and 29% in the nCPAP/NIPPV group (RR 0.29, 95%CI: 0.10-0.81). Evidence certainty was rated as low for all outcomes. CONCLUSIONS: NIV-NAVA as the primary respiratory support did not reduce the need for endotracheal intubation or surfactant therapy. NIV-NAVA seemed to reduce the reintubation rate after extubation in pre-term neonates.

Why all newborn hip screening programs have same results-a mini review.

All newborns are screened for developmental dysplasia of the hip (DDH), but countries have varying screening practices. The aim of this narrative mini review is to discuss the controversies of the screening and why it seems that all screening programs are likely to have same outcome. Different screening strategies are discussed alongside with other factors influencing DDH in this review. Universal ultrasound (US) has been praised as it finds more immature hips than clinical examination, but it has not been proven to reduce the rates of late-detected DDH or surgical management. Universal US screening increases initial treatment rates, while selective US and clinical screening have similar outcomes regarding late detection rates than universal US. This can be explained by the extrinsic factor affecting the development of the hip joint after birth and thus initial screening during the early weeks cannot find these cases.  Conclusion: It seems that DDH screening strategies have strengths and limitations without notable differences in the most severe outcomes (late-detected cases requiring operative treatment). Thus, it is important to acknowledge that the used screening policy is a combination of values and available resources rather than a decision based on clear evidence.

Risk of childhood neoplasms related to neonatal phototherapy- a systematic review and meta-analysis.

CONTEXT: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer. OBJECTIVE: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy. DATA SOURCES: The CENTRAL, PubMed, Scopus, and Web of Science databases. STUDY SELECTION: Observational studies regardless of design were included. DATA EXTRACTION: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools. RESULTS: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors. CONCLUSIONS: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding. IMPACT STATEMENT: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and.

Pediatric traumatic brain injury and early age multiple sclerosis in Finland: A nationwide register-based cohort study.

OBJECTIVE: Examine the link between pediatric traumatic brain injury (pTBI) and early-onset multiple sclerosis in Finland. METHODS: Conducted nationwide register study (1998-2018) with 28,750 pTBI patients (< 18) and 38,399 pediatric references with extremity fractures. Multiple sclerosis diagnoses from Finnish Social Insurance Institution. Employed Kaplan-Meier and multivariable Cox regression for probability assessment, results presented with 95% CI. RESULTS: Of 66 post-traumatic multiple sclerosis cases, 30 (0.10%) had pTBI, and 36 (0.09%) were in the reference group. Cumulative incidence rates (CIR) in the first 10 years were 46.5 per 100,000 (pTBI) and 33.1 per 100,000 (reference). Hazard ratio (HR) for pTBI was 1.10 (95% CI: 0.56-1.48).Stratified by gender, women's CIR was 197.9 per 100,000 (pTBI) and 167.0 per 100,000 (reference) after 15 years. For men, CIR was 44.6 per 100,000 (pTBI) and 34.7 per 100,000 (reference). In the initial 3 years, HR for female pTBI was 1.75 (95% CI: 0.05-6.32), and between years 3 and 20, it was 1.08 (95% CI: 0.51-1.67). For male patients, HR was 1.74 (95% CI: 0.69-4.39). SIGNIFICANCE: We did not find evidence of an association between pTBI and early-onset multiple sclerosis 20 years post-initial trauma.

The incidence of floorball injuries-A systematic review and meta-analysis.

OBJECTIVE: Floorball is a swift sport; players perform multiple quick turns during practices and games. The aim of this study was to examine the incidence of floorball injuries. In addition, we aimed to examine the differences in the incidences between sexes and anatomical locations. METHODS: The PubMed (National Library of Medicine), Web of Science (Clarivate), Scopus (Elsevier), and SPORTDiscus (EBSCO) databases were searched from inception to January 6th, 2023. A study was eligible for analysis if the number of injuries per exposure time was reported. The study protocol was prospectively registered in the PROSPERO database (CRD42023390659). RESULTS: The total pooled incidence of floorball injuries was 2.28 (confidence interval [CI] 1.27 to 4.10) injuries per 1000 h for all included studies. For females, the pooled incidence was 2.33 (CI 1.22 to 4.46) injuries per 1000 h, and for males, the incidence was 1.98 (CI 1.83 to 2.14) injuries per 1000-h. For adults, the pooled incidence was 3.11 (CI 1.58 to 6.12) injuries per 1000 h and for youths, the incidence was 1.40 (CI 0.50 to 3.94) injuries per 1000 h. CONCLUSIONS: The incidence of floorball injuries is high, especially among women. When considering the growing popularity of floorball, these pooled incidences serve as reference values for future injury prevention programs.

Randomized controlled trials reporting patient-reported outcomes with no significant differences between study groups are potentially susceptible to unjustified conclusions-a systematic review.

OBJECTIVES: Ceiling effect may lead to misleading conclusions when using patient-reported outcome measure (PROM) scores as an outcome. The aim of this study was to investigate the potential source of ceiling effect-related errors in randomized controlled trials (RCTs) reporting no differences in PROM scores between study groups. STUDY DESIGN AND SETTING: A systematic review of RCTs published in the top 10 orthopedic journals according to their impact factors was conducted, focusing on studies that reported no significant differences in outcomes between two study groups. All studies published during 2012-2022 that reported no differences in PROM outcomes and used parametric statistical approach were included. The aim was to investigate the potential source of ceiling effect-related errors-that is, when the ceiling effect suppresses the possible difference between the groups. The proportions of patients exceeding the PROM scales were simulated using the observed dispersion parameters based on the assumed normal distribution, and the differences in the proportions between the study groups were subsequently analyzed. RESULTS: After an initial screening of 2343 studies, 190 studies were included. The central 95% theoretical distribution of the scores exceeded the PROM scales in 140 (74%) of these studies. In 33 (17%) studies, the simulated patient proportions exceeding the scales indicated potential differences between the compared groups. CONCLUSION: It is common to have a mismatch between the chosen PROM instrument and the population being studied increasing the risk of an unjustified "no difference" conclusion due to a ceiling effect. Thus, a considerable ceiling effect should be considered a potential source of error.

The association between interpregnancy interval and gestational diabetes mellitus: A nationwide register-based study in Finland.

OBJECTIVE: Previous results on the association between interpregnancy interval (IPI) and gestational diabetes mellitus (GDM) have been contradictory. Hence, the aim of this study was to examine the association between IPI and GDM using high-quality nationwide register data. METHODS: All women with first and second pregnancies during our study period from the National Medical Birth Register during 2004-2018 were considered. A logistic regression model was used to assess the association between the length of the IPI and development of the GDM in the second pregnancy. Women were divided into three groups based on the length of the IPI: short IPI (0-11 months), normal IPI (12-47 months), and long IPI (48+ months). Adjusted odds ratios (aOR) with 95% CI were compared between the groups. RESULTS: A total of 47 078 women were included in the study. We found no evidence of difference when women with short IPI were compared with women with normal IPI (aOR 0.99, 95% CI 0.93-1.05). Women with long IPI had increased odds for the development of GDM when compared with women with normal IPI (aOR 1.28, 95% CI 1.19-1.38). In the logistic regression model for continuous IPI, the total odds for the development of GDM increased as the IPI increased (aOR 1.05 per year, 95% CI 1.03-1.06). CONCLUSION: The odds for the development of GDM increased as the IPI increased. This study's results serve as a clarion call for proactive measures in GDM prevention. Moreover, they advocate for intensified investigation into the underlying factors contributing to GDM among women with extended IPI. It is imperative that these insights inform both clinical practice and further research agendas, as we strive to safeguard maternal health and well-being.

Less Invasive Surfactant Administration Compared to Intubation, Surfactant, Rapid Extubation Method in Preterm Neonates: An Umbrella Review.

INTRODUCTION: In spontaneously breathing neonates, surfactant can be administered via thin catheter while enabling the own breathing (less invasive surfactant administration [LISA]). Alternatively, the neonate is intubated for surfactant delivery (intubation, surfactant, rapid extubation [INSURE]). Thus, the aim was to provide an overview of the efficacy of the LISA compared to INSURE. METHODS: We performed an umbrella review of previous meta-analyses including randomized controlled trials. We searched PubMed, Scopus, and Web of Science in July 2023. Two authors screened the search results, and systematic reviews with meta-analyses that focused on LISA versus INSURE were included. One author extracted, and another author validated the extracted data. AMSTAR-2 and ROBIS evaluations were performed by two authors independently. RESULTS: A total of 9 systematic reviews with meta-analyses were included. The quality according to AMSTAR-2 was high in one, moderate in one, low in three, and critically low in four. According to ROBIS, the risk of bias was low in three and high in six of the reviews. LISA was more effective than INSURE in preventing mechanical ventilation (8/8 reviews), death or BPD (4/4 reviews), death (3/9 reviews), and BPD (3/9 reviews). CONCLUSIONS: All the included systematic reviews and meta-analyses reported LISA to be more effective than INSURE in terms of need for mechanical ventilation and death or BPD. However, the quality of the published systematic reviews has been mostly deficient. Future systematic reviews should focus on reporting quality.

Fear of childbirth prolongs interpregnancy interval: A nationwide register-based quantile logistic regression analysis.

Introduction: It is not well studied how fear of childbirth (FOC) influences the interpregnancy interval (IPI). Thus, we aimed to analyze the association between FOC and the length of the IPI. Methods: All women having their first and second pregnancies during the study period (2004-2018) were gathered from the Finnish Medical Birth Register. A logistic regression model was used to assess the association between the FOC and subsequent length of the IPI. The length of the IPI was assessed separately for women with FOC in the first pregnancy, and for women who developed the FOC in the second pregnancy. IPIs with a length in the lower quartal were considered short IPIs, and length in the upper quartal as long IPIs. Adjusted odds ratios (aOR) with 95% CIs were compared between the groups. Results: A total of 52 709 women with short IPI (<1.05 years), 105 604 women with normal IPI, and 52 889 women with long IPI (>2.57 years) were included. A total of 3606 women had FOC in the first pregnancy, and a total of 11 473 had their first FOC diagnosis in the second pregnancy. Women with FOC in the first pregnancy had lower odds for short IPI (aOR 0.88, CI 0.81-0.95) and higher odds for long IPI (aOR 1.30, CI 1.21-1.40). Women with the first FOC diagnosis in the second pregnancy had higher odds for long IPI (aOR 1.68, CI 1.61-1.75), When only vaginal deliveries in the first pregnancy were included, women with FOC in the second pregnancy had lower odds for long IPI (aOR 0.71, CI 0.66-0.75) and higher odds for long IPI (aOR 1.52, CI 1.41-1.62), when only cesarean section was included. Conclusion: The main finding of this study was that women with FOC had notably higher odds for long IPI. The etiologic and background factors behind FOC should be better recognized and prevented, and FOC should not only be considered as a complicating factor for pregnancy and delivery but also a factor that strongly affects the desire of women to get pregnant again.

Effect of major trauma on the expected number of births in Finnish women: A nationwide population-based public data and register analysis.

BACKGROUND: The effect of major trauma on subsequent fertility is poorly described. If women have lower fertility after trauma, they would have a lower risk of anti-D mediated hemolytic disease of the fetus and newborn in a future pregnancy following the transfusion of RhD-positive blood to RhD-negative women during their resuscitation. STUDY DESIGN AND METHODS: Data was obtained from the Care Register for Health Care, National Medical Birth Register, and open access data from Statistic Finland to evaluate the effect of major trauma (traumatic brain injuries, spine, pelvic, hip/thigh fractures) on the age-specific number of births during years 1998-2018. The total number of births before a specific maternal age for different trauma populations was calculated and these were compared to the corresponding number of births in the general population. RESULTS: There were 50,923 injured women in this study. All injured women, including when analyzed by the nature of their injury, demonstrated lower expected numbers of births starting at approximately 28 years of age compared to the general population of women in Finland. At age 49, the expected number of births in the general population was approximately 1.8, whereas for all injured women 0.6, women with TBIs and spine fractures 0.6, women with pelvic fractures 0.5, and women with hip or thigh fractures 0.3. DISCUSSION: Injured women are predicted to have lower fertility rates compared to the general population of Finnish women. The lower fertility rate should be considered when planning a blood product resuscitation strategy for injured women.

High-flow nasal cannula use in pediatric patients for other indications than acute bronchiolitis-a scoping review of randomized controlled trials.

The objective of the study is to summarize current literature on high-flow nasal cannula (HFNC) use for different indications in pediatric patient excluding acute bronchiolitis and neonatal care. The study design is a systematic scoping review. Pubmed, Scopus, and Web of Science databases were searched in February, 2023. All abstracts and full texts were screened by two independent reviewers. Randomized controlled trials focusing on HFNC use in pediatric patients (age < 18 years) were included. Studies focusing on acute bronchiolitis and neonatal respiratory conditions were excluded. Study quality was assessed by Cochrane risk of bias 2.0 tool. The main outcomes are patient groups and indications, key outcomes, and risk of bias. After screening 1276 abstracts, we included 22 full reports. Risk of bias was low in 11 and high in 5 studies. We identified three patient groups where HFNC has been studied: first, children requiring primary respiratory support for acute respiratory failure; second, perioperative use for either intraprocedural oxygenation or postoperative respiratory support; and third, post-extubation care in pediatric intensive care for other than postoperative patients. Clinical and laboratory parameters were assessed as key outcomes. None of the studies analyzed cost-effectiveness.Conclusion: This systematic scoping review provides an overview of current evidence for HFNC use in pediatric patients. Future studies should aim for better quality and include economic evaluation with cost-effectiveness analysis.Protocol registration: Protocol has been published https://osf.io/a3y46/ .

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis.

OBJECTIVES: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. SEARCH STRATEGY: PubMed, Scopus and Web of Science databases were searched in March 2023. SELECTION CRITERIA: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo. DATA COLLECTION AND ANALYSIS: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. MAIN RESULTS: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence). CONCLUSIONS: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.

Noninvasive respiratory support preventing reintubation after pediatric cardiac surgery-A systematic review.

OBJECTIVE: To analyze the optimal postextubation respiratory support in pediatric cardiac surgery patients. DESIGN: Systematic review of randomized controlled trials. SETTING: Pediatric or neonatal intensive care units. PARTICIPANTS: All aged children (<16 years) having cardiac surgery and postoperative invasive ventilation. INTERVENTION: Noninvasive respiratory support, including high flow nasal cannula (HFNC), conventional oxygen therapy (COT), noninvasive positive pressure ventilation (NIPPV), continuous positive pressure (CPAP), and noninvasive high-frequency oscillatory ventilation (NHFOV). MEASUREMENT AND MAIN RESULTS: Studies were not pooled for statistical synthesis due to the limited number and quality of the included studies. Risk ratios with 95% confidence intervals were calculated for individual studies. A total of 167 studies were screened and six were included. The risk of bias was low in one, high in one, and had some concerns in four of the studies. Extubation failure (defined as reintubation) was the main outcome of interest. Risk ratio for reintubation was 0.10 (CI 0.02-0.40) and 1.07 (CI 0.16-7.26) in HFNC versus COT, 0.49 (CI 0.05-5.28) in HFNC versus NIPPV, 0.40 (CI 0.08-1.94) in HFNOV versus CPAP, 0.75 (CI 0.26-2.18) in HFNOV versus NIPPV, and 1.37 (CI 0.33-5.73) in CPAP versus NIPPV. Treatment durations did not differ between the groups. CONCLUSION: We did not find clear evidence of a difference in reintubation rates and other clinical outcomes between different noninvasive ventilation strategies. Evidence certainty was assessed to be very low due to the risk of bias, the small number of included studies, and high imprecision. Future quality studies are needed to determine the optimal postextubation support in pediatric cardiac surgery patients.

Inhaled nitric oxide in acute bronchiolitis: A systematic review and meta-analysis.

OBJECTIVE: Until date there is lack of effective therapies in acute bronchiolitis in infants. The aim was to analyze inhaled nitric oxide efficacy in acute bronchiolitis. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: Pediatric specialized healthcare. PATIENTS: All infants (age less than 2 years) having acute bronchiolitis, which requires emergency room visit or hospitalization. INTERVENTION: Inhaled nitric oxide. MAIN OUTCOME MEASURES: Need for intensive care unit admission. Secondary outcomes were length of hospital stay and adverse events. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) calculated by random-effects DerSimonian and Laird inverse variance method. Peto Odds ratios were used for rare outcomes. Evidence certainty assessed according to GRADE. RESULTS: 186 studies were screened and three included for analysis. Two had low risk of bias and one had some concerns. Three studies (166 infants) analyzed length of hospital stay and the duration was -11.3 h (CI: -26.8 to +4.2 h) shorter in the nitric oxide group. Evidence certainty was ranked as low. Overall adverse event rates were similar (3 studies, 166 infants, RR: 0.94, CI: 0.70-1.26), but treatment related harms were more common in nitric oxide group (2 studies, 98 infants, OR: 3.86, CI: 1.04-14.40). Evidence certainty in both was rated as low. CONCLUSIONS: Low certainty evidence suggests that inhaled nitric oxide does not reduce length of hospital stay but may have higher rate of treatment associated harms. Future studies with larger sample sizes are needed to better estimate both the efficacy and adverse events.

Azithromycin for acute bronchiolitis and wheezing episodes in children - a systematic review with meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to analyse the efficacy of azithromycin in acute bronchiolitis and wheezing. METHODS: PubMed, Scopus, and Web of Science databases were searched for randomized controlled trials comparing azithromycin to placebo in children <2 years of age. Main outcomes were progress of acute wheezing episode and recurrence of wheezing. We used random-effects model to calculate mean difference (MD) with 95% confidence interval (CI) or risk ratios (RR) with CI. RESULTS: We screened 1604 abstracts and included 7 studies. Risk of bias was low in three and had some concerns in four studies. Need for intensive care unit treatment was assessed in four studies (446 children) and the risk difference was 0.0% (CI -2.0 to 2.0; low quality evidence). Hospitalization duration was -0.27 days shorter in the azithromycin group (MD-0.27, CI -0.47 to -0.07; three studies; moderate quality evidence). Azithromycin did not prevent recurrence of wheezing (RR 0.84, CI 0.45-1.56; three studies), hospital readmissions (RR 1.14, CI 0.82-1.60; four studies). CONCLUSIONS: We found moderate quality evidence that azithromycin may reduce hospitalization duration. Low certainty evidence suggests that azithromycin does not reduce the need for intensive care unit treatment. Furthermore, azithromycin did not prevent wheezing recurrence. IMPACT: Azithromycin may reduce hospitalization time in acute bronchiolitis and wheezing episodes among children aged less than two. Azithromycin administrated during the acute wheezing period, does not have preventive effect on wheezing recurrence. Azithromycin seemed to have similar adverse event profile than placebo. Future studies with clinically relevant outcomes, and sufficient sample sizes are needed, before implementing azithromycin into clinical use.