Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL, and two trials registers in October 2022, with backwards and forwards citation analysis on the new studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, glasses, and gargling) to prevent respiratory virus transmission.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 11 new RCTs and cluster-RCTs (610,872 participants) in this update, bringing the total number of RCTs to 78. Six of the new trials were conducted during the COVID-19 pandemic; two from Mexico, and one each from Denmark, Bangladesh, England, and Norway. We identified four ongoing studies, of which one is completed, but unreported, evaluating masks concurrent with the COVID-19 pandemic. Many studies were conducted during non-epidemic influenza periods. Several were conducted during the 2009 H1N1 influenza pandemic, and others in epidemic influenza seasons up to 2016. Therefore, many studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Adherence with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included 12 trials (10 cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza-like illness (ILI)/COVID-19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate-certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory-confirmed influenza/SARS-CoV-2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate-certainty evidence). Harms were rarely measured and poorly reported (very low-certainty evidence). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). We are very uncertain on the effects of N95/P2 respirators compared with medical/surgical masks on the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 3 trials, 7779 participants; very low-certainty evidence). N95/P2 respirators compared with medical/surgical masks may be effective for ILI (RR 0.82, 95% CI 0.66 to 1.03; 5 trials, 8407 participants; low-certainty evidence). Evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirators compared to medical/surgical masks probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 5 trials, 8407 participants; moderate-certainty evidence). Restricting pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies (very low-certainty evidence).  One previously reported ongoing RCT has now been published and observed that medical/surgical masks were non-inferior to N95 respirators in a large study of 1009 healthcare workers in four countries providing direct care to COVID-19 patients.  Hand hygiene compared to control Nineteen trials compared hand hygiene interventions with controls with sufficient data to include in meta-analyses. Settings included schools, childcare centres and homes. Comparing hand hygiene interventions with controls (i.e. no intervention), there was a 14% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.86, 95% CI 0.81 to 0.90; 9 trials, 52,105 participants; moderate-certainty evidence), suggesting a probable benefit. In absolute terms this benefit would result in a reduction from 380 events per 1000 people to 327 per 1000 people (95% CI 308 to 342). When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.94, 95% CI 0.81 to 1.09; 11 trials, 34,503 participants; low-certainty evidence), and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials, 8332 participants; low-certainty evidence), suggest the intervention made little or no difference. We pooled 19 trials (71, 210 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. Pooled data showed that hand hygiene may be beneficial with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.83 to 0.94; low-certainty evidence), but with high heterogeneity. In absolute terms this benefit would result in a reduction from 200 events per 1000 people to 178 per 1000 people (95% CI 166 to 188). Few trials measured and reported harms (very low-certainty evidence). We found no RCTs on gowns and gloves, face shields, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory-confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

BACKGROUND: Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation. METHODS: An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF. RESULTS: We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes). CONCLUSIONS: The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient's characteristics and recognized international guidelines.

[The impact of the COVID-19 pandemic on the Italian and foreign population in the various phases: the results of an interregional multicentre project]. / L'impatto della pandemia di COVID-19 nella popolazione italiana e straniera residente nelle diverse fasi: i risultati di un progetto multicentrico inter-regionale.

OBJECTIVES: to analyze the difference of the SARS-CoV-2 infection impact between Italian and foreigner subjects, evaluating the trend of infections and access to diagnostic tests (molecular or antigenic swabs for the detection of SARS- CoV-2) in the two different populations, inducing the detection of new positive cases in the population. DESIGN: retrospective population study for the period February 2020-June 2021. SETTING AND PARTICIPANTS: Italian and foreign resident population on 1st January of the years 2020 and 2021 in the Regions participating to the project: Piedmont, Lombardy, Veneto, Emilia-Romagna (Northern Italy), Tuscany, Lazio (Central Italy), and Sicily (Southern Italy). MAIN OUTCOME MEASURES: in the two populations, for every week and aggregated by macropandemic period were calculated: • the test rate (people tested on the population); • the swab positivity rate (positive subjects on those who are tested); • the new positives (positive subjects on study population); • the percentage of foreigners among the new positive cases. The ratio of the value of the indicators in the foreign and Italian populations (with 95% confidence interval) was calculated to evaluate the association between nationality (Italian vs not Italian) and outcome. The analyses were conducted at the regional level and at pool level. RESULTS: the trend of new positives by nationality (Italian vs not Italian) has a similar tendency in the different pandemic waves. However, the incidence of new positives during pandemic waves among foreigners is lower than in Italians, while it tends to increase during intermediate periods. Except for the summer periods, foreigners are less tested than Italians, but the percentage of new positives out of the total of new ones tested is higher among foreigners compared to Italians. The relative weight of new positives among foreigners tends to increase in periods with the greatest risk of inflow of SARS-CoV-2 for foreigners. CONCLUSIONS: the epidemic trends in the two populations are similar, although foreigners tend to show lower incidence values, probably in part because they are tested less frequently. Furthermore, in foreigners compared to Italians, there is a greater risk of contracting SARS-CoV-2 infection, especially in periods of relaxation of containment Coronavirus measures, reopening of national borders, production and commercial activities.

[Impact of COVID-19 on the immigrant population in the Veneto Region (Northern Italy), by geographical area of origin]. / Impatto del COVID-19 nella popolazione immigrata in Veneto, per area geografica di provenienza.

OBJECTIVES: to examine the differences in SARS-CoV-2 infection and hospitalization rates among migrant populations in Veneto Region (Northern Italy), according to the geographic area of origin. SETTING AND PARTICIPANTS: all residents in Veneto Region aged <65 years were included in the analyses. All subjects infected by SARS-CoV-2 and hospitalized for COVID-19 were identified by means of the regional biosurveillance system. MAIN OUTCOME MEASURES: age- and gender-specific infection and hospitalization rates were stratified by geographic area of origin and were estimated using the number of incident cases over the resident population in Veneto on 01.01.2021. Incidence rate ratios (IRR) for infection and hospitalization rates were estimated using a Poisson model, adjusted for age and gender, among migrants compared to Italians. RESULTS: compared to Italians, SARS-CoV-2 infection rates were significantly higher among migrants from Central and South America and Central and South Asia, lower among those from North Africa and High-Income Countries (HIC), and were approximately halved for those coming from Other Asian Countries (mainly represented by China). Hospitalization rates were significantly higher for all migrant populations when compared to Italians, with the exception of those coming from HIC. Neither age nor gender seemed to modify the association of the geographic area of origin with SARS-CoV-2 infection and hospitalization rates. IRR for SARS-CoV-2 infection of migrants compared to Italians showed how migrants from Other Asian Countries had the lowest infection rates (-53%), followed by people from HIC (-25%), North Africa (-21%), and Eastern Europe (-10%). Higher infection rates were present for Central and South America and Central and South Asia (+17% and +10, respectively). Hospitalization rates were especially high among migrants from Central and South Asia, Africa, and Central and South America, ranging from 1.84 to 3.14 times those observed for Italians. CONCLUSIONS: a significant heterogeneity in SARS-CoV-2 infection and hospitalization rates of migrant populations from different geographic areas of origin were observed. The significantly lower incidence rate ratio for infections, compared to that observed for hospitalizations, is suggestive of a possible under-diagnosis of SARS-CoV-2 infection among migrant populations. Public health efforts should be targeted at increasing support among migrants to contrast the spread of the pandemic by potentiating vaccination campaigns, contact tracing, and COVID-19 diagnostic tests.

Access to SARS-CoV-2 diagnostic tests: are there barriers for the immigrants in Italy?

OBJECTIVES: to describe the epidemiology of SARS-CoV-2 infection in relation with the use of nasal swabs in the immigrant population in Italy, using data from the COVID-19 national surveillance system and to verify if a difference is present comparing natives and immigrant. DESIGN: descriptive study based on longitudinal health-administrative data. SETTING AND PARTICIPANTS: general population of six Italian Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany, Lazio) covering about 55% of the resident population and 72% of foreigners' population. MAIN OUTCOME MEASURES: regional rates of access to at least a nasal swab, separately by country of origin. RESULTS: across all the periods, a lower rate in the foreigners' group was observed, with the only exception of the period May-June 2021. Considering separately High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs), a higher proportion of nasal swabs performed in people coming from HDC with respect to HMPCs and natives was noticed. This observation is consistent in males and females. CONCLUSIONS: during the first wave of the pandemic, Italians have had a higher proportion of nasal swabs compared to migrants across all Regions. This difference disappeared in the following periods, probably due to a major availability of diagnostic tests.

[SARS-CoV-2 epidemic among Italians e resident immigrant population: differential incidence from an interregional multicentre study]. / L'epidemia di SARS-CoV-2 nella popolazione italiana e straniera: differenze di incidenza che emergono da uno studio multicentrico interregionale.

OBJECTIVES: to describe differences in the incidence of SARS-CoV-2 infections between Italians and foreigners residing in seven Italian Regions during the different phases of the pandemic and by gender. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: all confirmed SARS-CoV-2 infections from 02.02. 2020 to 16.07.2021 in the seven Regions under study were included. Italian resident population calculated by the National Institute of Statistics as of 01.01.2020 was used to calculate the rates. The considered period is divided into 5 sub-periods (phases). MAIN OUTCOME MEASURES: number of confirmed SARS-CoV-2 infections in the five phases of the pandemic and crude rates by citizenship (Italian vs foreign). Distribution of infections by age group and by week. Crude and age-adjusted incidence rates ratios (IRR) were calculated, by Region, gender, and phase of the pandemic. RESULTS: an epidemic curve delay was observed in foreigners in the first phase of the epidemic, in particular in the northern Regions, the most affected in that phase. The first phase of the epidemic was characterized by a greater proportion of cases occurred in people aged over 60 years than the other phases, both in Italians and in foreigners. The incidence among foreigners is higher during the summer of 2020 (intermediate period: June-September 2020) and during the last period (May-July 2021) in all Regions. The overall figure shows a lower incidence among foreigners than Italians, except for males in Tuscany. CONCLUSIONS: the lower incidence rates among foreigners should be interpreted with caution as the available data suggest that it is at least partly attributable to less access to diagnostic tests. Regional differences found in the study deserve further research together with the effect of gender and country of origin.

[Hospital assistance for COVID-19: a comparison between non-Italian and Italian resident population in five Italian Regions since the beginning of the pandemic until June 2021]. / Un confronto tra italiani e stranieri residenti nell'assistenza ospedaliera per COVID-19 in cinque Regioni italiane da inizio pandemia a giugno 2021.

OBJECTIVES: to describe trends of overall and intensive care hospitalization for COVID-19 since the beginning of the pandemic in Italy until June 2021, and to compare the results between foreign and Italian population. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: hospital discharges of 28 million people living in Lombardy, Piedmont, Emilia-Romagna (Northern Italy), Toscana and Lazio (Central Italy) occurred between 22.02.2020 and 02.07.2021 in the hospitals located in each considered Region. MAIN OUTCOME MEASURES: two weekly outcomes were examined: 1. the overall number of COVID-19 hospitalizations; 2. the number of COVID-19 hospitalizations in intensive care units. RESULTS: a higher COVID-19 overall and intensive care unit hospitalization was found among the foreign population compared to Italians. The association emerged only after the adjustment for age, and it was consistent among all Regions, though less marked in Lombardy. The association varied across epidemic phases. CONCLUSIONS: the issue of vulnerability of migrants to the risk of severe COVID-19 calls for a diversity-sensitive approach in prevention. The specific country of origin and the prevalence of preventable co-morbidities that are often underestimated in the migrant populations, and related to COVID-19 complications, should be taken into consideration in future analyses.

Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy.

OBJECTIVES: To ascertain if the use of hydroxychloroquine(HCQ)/cloroquine(CLQ) and other conventional DMARDs (cDMARDs) and rheumatic diseases per se may be associated with COVID-19-related risk of hospitalization and mortality. METHODS: This case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. The risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis comparing HCQ/CLQ vs MTX, vs other cDMARDs and vs non-use of these drugs. The presence of rheumatic diseases vs their absence in a non-nested population was investigated. RESULTS: A total of 1275 patients hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of MTX, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization [odds ratio (OR) 0.83 (95% CI 0.69, 1.00)] or mortality [OR 1.19 (95% CI 0.85, 1.67)] was observed. A lower risk was found when comparing HCQ/CLQ use with the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either MTX monotherapy [OR 1.19 (95% CI 1.05, 1.34)] or other cDMARDs [OR 1.21 (95% CI 1.08, 1.36)] vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. CONCLUSION: HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19-related outcomes. The use of other cDMARDs was associated with an increased risk when compared with non-use and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably due to immunosuppressive action.

[Residential cohort study to assess the impact of emissions released by a cement plant on the health status of the population residing in Pederobba (Veneto Region, Northern Italy)]. / Studio di coorte residenziale per valutare l'impatto delle emissioni di un cementificio sullo stato di salute della popolazione di Pederobba (Treviso).

OBJECTIVES: to assess the impact of a cement plant emissions on mortality, hospitalizations, and cancer incidence in the residents of the municipality of Pederobba (Veneto Region, Northern Italy). DESIGN: retrospective residential cohort study. SETTING AND PARTICIPANTS: the study was conducted in Pederobba and in 7 neighbouring municipalities (Cavaso Del Tomba, Cornuda, Crocetta del Montello, Monfumo, Segusino, Valdobbiadene, Vidor). The cohort included 12,116 residents in Pederobba (151,784 person-years) and 49,004 residents in the neighbouring municipalities (660,268 person-years) in the period 1996-2017. On the basis of the model estimate of the annual average concentration of nitrogen dioxide (NO2), the municipality of Pederobba was divided into an area with higher exposure of NO2 and another one at lower exposure of NO2. Two comparisons were made: the first between the residents in Pederobba and residents in the neighbouring municipalities; the second between people residing in Pederobba in the higher and in the lower exposure areas. MAIN OUTCOME MEASURES: analysis of cause-specific mortality and hospitalization and cancer incidence, with particular attention to the diseases for which there is evidence of association with exposure to air-pollutants. For cancer incidence, available data were limited to the municipalities of Pederobba, Cavaso Del Tomba, Cornuda, Crocetta del Montello, and Monfumo for the period 1996-2015. RESULTS: the comparison among Pederobba and the 7 neighbouring municipalities showed that within Pederobba residents there was:ʉۢ a slight increase in the risk of death from all causes in women, due to circulatory diseases (HR 1.29; 95%CI 1.15-1.45), in particular ischaemic heart disease (HR 1.55; 1.27-1.89) and cerebrovascular diseases (HR 1.35; 1.06-1.72);ʉۢ a moderate increase in hospitalizations for circulatory diseases, such as heart failure (HR 1.17; 1.00-1.37) and cerebrovascular diseases (HR 1.41; 1.17 -1.70), especially in elderly women;ʉۢ a slight increase in hospitalizations for respiratory diseases, especially in older women (HR 1.19; 1.04-1.37);ʉۢ no difference were observed in cancer incidence, neither for all nor for single cancer sites, in both genders.The comparison between residents in the higher exposure area and those in the lower exposure area showed no difference in mortality, hospitalizations, and cancer incidence. CONCLUSIONS: higher mortality and hospitalization rates from circulatory and respiratory causes detected in Pederobba compared to the neighbouring municipalities were not confirmed by the comparison between residents in the higher and in the lower exposure area. Overall, data did not show a clear, well-characterized relationship between the exposure to pollutants emitted by the cement plant and the onset of chronic diseases. The excess of mortality and hospitalization for cardiovascular and cerebrovascular diseases, reported especially in older women, deserves further investigation, because of the complex cause-effect relations of these diseases.

Impact of laparoscopic approach on the short-term outcomes of elderly patients with colorectal cancer: a nationwide Italian experience.

INTRODUCTION: The laparoscopic approach is increasingly adopted in colorectal cancer surgery; however, its role in elderly patients is controversial. We sought to examine the relationship between age and short-term outcomes following laparoscopic surgery for colorectal cancer (CRC). METHODS: Data of patients 65 + years old who underwent laparoscopic surgery for CRC between 2002 and 2014 were retrieved from the administrative National Italian Hospital Discharge Dataset. Patients were divided into three age categories (65-74, 75-84, and 85 +). The impact of age on length of stay, 30-day readmission, in-hospital mortality, and postoperative complications was evaluated. RESULTS: During the study period, 47,704 patients underwent laparoscopic surgery for CRC. The median postoperative length of stay was 9 days, and 30-day readmission and in-hospital mortality were 4.4% and 0.9%, respectively. Age was found to be an independent risk factor of prolonged length of stay and increased in-hospital mortality. With respect to patients in 65-74 years age category, patients aged 75-84 years and those aged 85 + years had a higher risk of complications (OR 1.43, 95% CI 1.36-1.50, and OR 2.00, 95% CI 1.83-2.17, respectively). However, no statistically significant association was found between age and anastomotic leakage or surgical site infection (p = 0.29, and p = 0.58, respectively). CONCLUSIONS: In patients with CRC who underwent laparoscopic surgery, age was found to be an independent risk factor for prolonged length of stay, in-hospital mortality, and global postoperative complications. These findings should be considered when planning laparoscopic surgery in elderly patients.