Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis was designed in order to ascertain the effectiveness of respiratory syncytial virus (RSV) vaccination in preventing lower respiratory tract diseases (LRTD) in older adults (age ≥ 60 years). Studies reporting on randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) and the preprint repository medRxiv until 31 March 2024. A total of nine studies were eventually included, two of which were conference proceedings. Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). The meta-analysis documented a pooled vaccine efficacy of 81.38% (95% confidence interval (95% CI) 70.94 to 88.06) for prevention of LRTD with three or more signs/symptoms during the first RSV season after the delivery of the vaccine. Follow-up data were available for RSVPreF3 (2 RSV seasons), RSVpreF (mid-term estimates of second RSV season), and mRNA-1345 (12 months after the delivery of the primer), with a pooled VE of 61.15% (95% CI 45.29 to 72.40). After the first season, the overall risk for developing RSV-related LRTD was therefore substantially increased (risk ratio (RR) 4.326, 95% CI 2.415; 7.748). However, all estimates were affected by substantial heterogeneity, as suggested by the 95% CI of I2 statistics, which could be explained by inconsistencies in the design of the parent studies, particularly when dealing with case definition. In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions.

Impact of Nirsevimab Immunization on Pediatric Hospitalization Rates: A Systematic Review and Meta-Analysis (2024).

A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I2 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman's r = -0.546, p = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting (ß = 0.001, 95% CI -0.001 to 0.002; p = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions.

Occurrence of Central Nervous System Complications of Respiratory Syncytial Virus Infections: A Systematic Review with Meta-Analysis.

An increasing base of evidence suggests that respiratory syncytial virus (RSV) infections may be associated with neurological complications. In accord with the PRISMA statement, we performed a systematic review and meta-analysis on the occurrence of encephalitis and encephalopathy associated with documented RSV infections. PubMed, Embase, and Scopus databases were searched for eligible observational studies published up to 10 April 2024. Raw data included the occurrence of RSV infections among cases of encephalitis and/or encephalopathy and cases of encephalitis and/or encephalopathy among series of RSV infections. Data were pooled in a random effects model. Case reports were also collected, and their data pooled as a cumulative series. Heterogeneity was assessed using the I2 measure, while reporting bias was assessed by means of funnel plots and regression analysis. A total of 15 studies for a total of 7719 RSV infections and 1631 cases of encephalitis were analyzed. Moreover, 27 case reports and case series were retrieved, for a total of 84 individual cases of encephalitis/encephalopathy occurring during a documented RSV infection. A pooled prevalence of 2.20 cases of encephalitis/encephalopathy per 100 RSV cases (I2 = 99%) was calculated, while a prevalence of RSV infections among cases of encephalitis/encephalopathy was estimated to 3.53 per 100 cases for studies on respiratory specimens (I2 = 48%) and 0.37 per cases on central nervous system (CNS) specimens (I2 = 0%). Detection of RSV within the CNS was relatively rare (17.86% of pooled case reports), being associated with male gender (adjusted odds ratio [aOR] 5.021, 95% confidence interval [95%CI] 1.104 to 22.831) and recovery with long-term sequelae (aOR 5.699, 95%CI 1.152; 28.183). Case fatality ratio was estimated to be 0.43 per 100 cases on observational studies and 10.71% in case reports, a difference likely due to publication bias. In summary, RSV represented a not frequent but notable cause of encephalitis/encephalopathy in adults and children. The paucity of available studies not only recommends a cautious appraisal of our results but stresses the clinical significance of future studies on incident cases of encephalitis and/or encephalopathy.

Epidemiology of Legionnaires' Disease in Italy, 2004-2019: A Summary of Available Evidence.

Legionnaires' disease (LD) incidence has been increasing in several European countries since 2011. Currently, Italy is experiencing high notification rates for LD, whose cause still remains scarcely understood. We sought to summarize the available evidence on the epidemiology of LD in Italy (2004-2019), characterizing the risk of LD by region, sex, age group, and settings of the case (i.e., community, healthcare, or travel-associated cases). Environmental factors (e.g., average air temperatures and relative humidity) were also included in a Poisson regression model in order to assess their potential role on the annual incidence of new LD cases. National surveillance data included a total of 23,554 LD cases occurring between 2004 and 2019 (70.4% of them were of male gender, 94.1% were aged 40 years and older), with age-adjusted incidence rates increasing from 1.053 cases per 100,000 in 2004 to 4.559 per 100,000 in 2019. The majority of incident cases came from northern Italy (43.2% from northwestern Italy, 25.6% from northeastern Italy). Of these, 5.9% were healthcare-related, and 21.1% were travel-associated. A case-fatality ratio of 5.2% was calculated for the whole of the assessed timeframe, with a pooled estimate for mortality of 0.122 events per 100,000 population per year. Poisson regression analysis was associated with conflicting results, as any increase in average air temperature resulted in reduced risk for LD cases (Incidence Rate Ratio [IRR] 0.807, 95% Confidence Interval [95% CI] 0.744-0.874), while higher annual income in older individuals was associated with an increased IRR (1.238, 95% CI 1.134-1.351). The relative differences in incidence between Italian regions could not be explained by demographic factors (i.e., age and sex distribution of the population), and also a critical reappraisal of environmental factors failed to substantiate both the varying incidence across the country and the decennial trend we were able to identify.

The relationship between blood pressure and pain.

The relationship between pain and hypertension is potentially of great pathophysiological and clinical interest, but is poorly understood. The perception of acute pain initially plays an adaptive role, which results in the prevention of tissue damage. The consequence of ascending nociception is the recruitment of segmental spinal reflexes through the physiological neuronal connections. In proportion to the magnitude and duration of the stimulus, these spinal reflexes cause the activation of the sympathetic nervous system, which increases peripheral resistances, heart rate, and stroke volume. The response also involves the neuroendocrine system, and, in particular, the hypothalamic-pituitary-adrenal axis, in addition to further activation of the sympathetic system by adrenal glands. However, in proportion to an elevation in resting blood pressure, there is a contemporary and progressive reduction in sensitivity to acute pain, which could result in a tendency to restore arousal levels in the presence of painful stimuli. The pathophysiological pattern is significantly different in the setting of chronic pain, in which the adaptive relationship between blood pressure and pain sensitivity is substantially reversed. The connection between acute or chronic pain and cardiovascular changes is supported observationally, but some of this indirect evidence is confirmed by experimental models and human studies. The pain regulatory process and functional interaction between cardiovascular and pain regulatory systems are briefly reviewed. Various data obtained are described, together with their potential clinical implications.