Development of a network model to implement the HPV vaccination coverage.

Background: The vaccination coverage of a population is the usual indicator of the effectiveness of vaccination strategies. The study aims to evaluate the effectiveness of an organizational and communication network to implement Human Papilloma Virus (HPV) vaccination coverage both in males and females in the Center Tuscany Local Health Authority. Study design: Experimental study. Materials and methods: In January 2022, a retrospective study was conducted on anti-HPV vaccine coverage (full cycle), of those born from 2007 to 2010, in the Empoli Territorial Area of Florence (240 thousand inhabitants) under the Center Tuscany Local Health Authority. In February 2022, a project (meetings with general practitioners and pediatricians, communication through local media, increased opening hours of vaccination clinics and continuous monitoring of vaccination status) started to recover the females and males non-compliant; in the first five months, in addition to guaranteeing the offer to the reference cohort, it aimed to recover the 2007, 2008 and 2009 cohorts, while in the following six months the anti-HPV vaccine offer was expanded for the 2010 cohort. Results: In January 2022, for all cohorts the average total coverages were 49.2% (49.1% for females and 49.5% for males), while in December 2022 they were 63.9% (65.8% for females and 62.3% for males). Coverage increased by 15.6% (+14.2% for females and +16.8% for males) for the 2007 birth cohort, by 22.3% (+20.6% for females and +23.7% for males) for the 2008 cohort and by 20.9% (+31.4% for females and +10.6% for males) for the 2009 cohort. Conclusions: This model in force in the whole Center Tuscany Local Health Authority for a few years and already activated in the previous Local Health Authority of Empoli, now called Empoli Territorial Area, has allowed to implement the Human Papilloma Virus vaccine coverage for both genders.

Every cockroach is beautiful to his mother's eyes"? A multicentric study on the perception of child's health status according to the parent.

Introduction: Childhood obesity is a social health problem in the Western World and an important goal is to analyze and correct risk factors. However, part of the problem could be determined by a different perception of the weight. Material and methods: In October 2019, we conducted a cross-sectional study in which a questionnaire was administered to the parents of primary and secondary school children in South-East Tuscany, Italy. The aim was to determine the association between children's Body Mass Index (BMI) and the parent's perception. Results: Analysis was carried out on 1,405 complete questionnaires. We found that most parents wrongly perceive the weight of their children. 88.3% of parents with obese children believe that their children are of normal weight or only "a little overweight". 67.6% of parents who have overweight children think that their children are of normal weight (p < 0.001). Conclusions: Our results show a misperception of the weight of the children in the parents eyes. The acquisition of healthy behaviour during childhood is extremely important for health in adulthood and for avoiding the onset of associated diseases. Therefore, food education becomes a crucial objective. Children and parents need to increase consciousness of the correct weight and diseases resulting from bad nutrition.

Factors Influencing the Healthcare Workers' Willingness to Receive the COVID-19 Booster Dose in Tuscany (Italy).

BACKGROUND: The World Health Organization has defined vaccine hesitancy as behavior influenced by several factors, including trust in the vaccine itself or its provider or the perceived need for vaccination. The aim of this study was to investigate the factors influencing the willingness to receive the COVID-19 vaccine among the employees and healthcare professionals of the Central Tuscany Local Health Authority (CT-LHA) in Italy. METHODS: From July to October 2022, a cross-sectional study was conducted. An online questionnaire was administered to 7000 employees of the CT-LHA. The questionnaire analyzed the factors that influenced receiving the booster dose of the COVID-19 vaccine. The sample was stratified by gender, age, type of occupation (healthcare or non-healthcare workers), and seniority. Incomplete questionnaires were excluded. A chi-squared test was performed through STATA. The significance level was set at 95%. RESULTS: Of the questionnaires administered, 1885 (26.9%) questionnaires were eligible for the study. In the previous vaccination campaign, the healthcare workers (HCWs) considered the vaccine used by CT-LHA as safe, in contrast to non-healthcare workers (N-HCWs), who considered it less secure (p < 0.05). The HCWs showed a higher propensity for vaccine safety to receive the booster dose than N-HCWs. N-HCWs appeared to be less affected by an updated booster dose than HCWs (p < 0.05). CONCLUSIONS: The factors studied appear to influence HCWs differently from N-HCWs. Both HCWs and N-HCWs would choose an upgraded mRNA vaccine for the booster dose.

Can a UV-C box help the cinema industry by disinfecting video cameras?

Introduction: UV-C has proven to be an effective virucide and microbicide, and its cost-effectiveness allowed it to spread as a disinfecting procedure in different environments. Methods: The study aims to determine the microbicide activity on Staphylococcus aureus, Escherichia coli and SARS-CoV-2 of the UV-C Boxer by Cartoni S.p.A. Three separate experiments were performed to assess the effectiveness of the UV-C disinfection device on different materials, directly on surfaces of a video camera and on a specific carrier for SARS-CoV-2. Results: In all three experiments, a significant abatement of bacterial and viral contamination was reached after 60 seconds on carriers and after 3 minutes on all examined surfaces of the video camera, with a higher reduction on glass carriers. Conclusions: UV-C devices may be a valuable tool to implement in the working routine to achieve a higher level of safety in work environments.

Identifying the Drivers of Inter-Regional Patients' Mobility: An Analysis on Hospital Beds Endowment.

BACKGROUND: In a Beveridgean decentralized healthcare system, like the Italian one, where regions are responsible for their own health planning and financing, the analysis of patients' mobility appears very interesting as it has economic and social implications. The study aims to analyze both patients' mobility for hospital rehabilitation and if the beds endowment is a driver for these flows; Methods: From 2011 to 2019, admissions data were collected from the Hospital Discharge Cards database of the Italian Ministry of Health, population data from the Italian National Institute of Statistics and data on beds endowment from the Italian Ministry of Health website. To evaluate patients' mobility, we used Gandy's Nomogram, while to assess if beds endowments are mobility drivers, we created two matrices, one with attraction indexes (AI) and one with escape indexes (EI). The beds endowment, for each Italian region, was correlated with AI and EI. Spearman's test was carried out through STATA software; Results: Gandy's Nomogram showed that only some northern regions had good hospital planning for rehabilitation. A statistically significant correlation between beds endowment and AI was found for four regions and with EI for eight regions; Conclusions: Only some northern regions appear able to satisfy the care needs of their residents, with a positive attractions minus escapes epidemiological balance. The beds endowment seems to be a driver of patients' mobility, mainly for escapes. Certainly, the search for mobility drivers needs further investigation given the situation in Molise and Basilicata.

Effectiveness of near-UVA in SARS-CoV-2 inactivation.

This experimental study aimed to determine the activity of a near-UVA (405 nm) LED ceiling system against the SARS-CoV-2 virus. The ceiling system comprised 17 near-UVA LED lights with a radiant power of 1.1 W/each centred at 405 nm wavelength. A 96-multiwell plate, fixed to a wooden base, was inoculated with suspensions of VERO E6 cell cultures infected with SARS-CoV-2 virus and irradiated at a distance of 40 cm with a dose of 20.2 J/cm2 for 120 min. The collected suspensions were transferred to VERO cell culture plates and incubated for 3 days. The maximum measurable log reduction obtained, starting from a concentration of 107.2 TCID50/mL, was 3.0 log10 and indicated inhibition of SARS-CoV-2 replication by the near-UVA LED ceiling system. Near-UVA light at a 405-nm wavelength is emerging as a potential alternative treatment for localised infections and environmental decontamination because it is far less harmful to living organisms' cells than UV-C irradiation.

The Structures and Activities of Health Promotion in the Italian NHS.

BACKGROUND: In Italy, the Ministry of Health is the main decision-making entity in healthcare. The local health authorities (LHAs) are responsible for health promotion (HP) activities, based on national and regional health plans. Our aim was to investigate the structured activities of HP in Italy at national, regional, and territorial levels. METHODS: From February 2020 to July 2021, we searched for online information about the structures, projects, and responsibilities at the different levels mentioned above. The sources were the official sites of the Ministry of Health, the regions, and LHAs. RESULTS: During the "prevalence period" of 2014-2021, we found 41 active facilities dedicated to HP: 7 complex operational units and 34 simple units. The other 30 facilities also had HP activities despite the absence of dedicated units. The most discussed topic seemed to be physical activity (63%), followed by addictions (53%), nutrition (48%), and prevention (33%); in the queue appeared dental hygiene and family/parenting (both at 7%). The LHA of the City of Turin and the LHA of Salerno had the most significant number of topics. CONCLUSIONS: The results showed great heterogeneity, in the Italian context, concerning HP activities. We assume that the phenomenon depends on reduced attention to the digitalization of information. The Italian Society of Health Promotion is pursuing the goal of the construction of an organic system of HP-with its own articulations, competencies, and scientific and operational goals-at different levels, thus transcending the health care system (which is often powerless in regulatory activity) and providing the one harbinger of the most promising results in terms of cost/benefit.

Efficacy of violet-blue light to inactive microbial growth.

The increase in health care-associated infections and antibiotic resistance has led to a growing interest in the search for innovative technologies to solve these problems. In recent years, the interest of the scientific community has focused on violet-blue light at 405 nm (VBL405). This study aimed to assess the VBL405 efficiency in reducing microbial growth on surfaces and air. This descriptive study run between July and October 2020. Petri dishes were contaminated with P. aeruginosa, E. coli, S. aureus, S. typhimurium, K. pneumoniae and were placed at 2 and 3 m from a LED light source having a wavelength peak at 405 nm and an irradiance respectively of 967 and 497 µW/cm2. Simultaneously, the air in the room was sampled for 5 days with two air samplers (SAS) before and after the exposition to the VBL405 source. The highest microbial reduction was reached 2 m directly under the light source: S. typhimurium (2.93 log10), K. pneumoniae (2.30 log10), S. aureus (3.98 log10), E. coli (3.83 log10), P. aeruginosa (3.86 log10). At a distance of 3 m from the light source, the greatest reduction was observed for S. aureus (3.49 log10), and P. aeruginosa (3.80 log10). An average percent microbial reduction of about 70% was found in the sampled air after 12 h of exposure to VBL405. VBL405 has proven to contrast microbial growth on the plates. Implementing this technology in the environment to provide continuous disinfection and to control microbial presence, even in the presence of people, may be an innovative solution.

Inter-Regional Patients' Migration for Hospital Orthopedic Intensive Rehabilitation: The Italian Experience.

BACKGROUND: Following the introduction of administrative federalism in the Italian National Health Service, inter-regional patients' mobility has become increasingly relevant because, in addition to being an indirect index of the quality of care, it has important economic and financial implications. This study aimed to evaluate the fulfillment of the need for hospital orthopedic intensive rehabilitation on site and care-seeking patients' migration to other regions. METHODS: From 2011 to 2019, the data of intensive orthopedic rehabilitation extracts from the Hospital Discharge Cards provided by Italian Ministry of Health were analyzed. We studied the hospital networks of every Italian region (catchment areas). The epidemiological flows of inter-regional mobility were analyzed with Gandy's Nomogram, while the financial flows were analyzed through Attraction Absorption and Escape Production Indexes. RESULTS: Gandy's Nomogram showed that only Piedmont, Lombardy, A.P. of Trento, E. Romagna, Umbria and Abruzzo had good public hospital planning for intensive orthopedic rehabilitation, with a positive balance for all studied periods. Lombardy, E. Romagna, Piedmont, Veneto and Latium have absorbed approximately 70% of all financial flows (about EUR 60.5 million). CONCLUSIONS: Only six regions appear to be able to satisfy the care needs of their residents, with a positive epidemiological and financial balance for all studied periods.

Predicting Healthcare-associated Infections: are Point of Prevalence Surveys data useful?

Introduction: Since 2012, the European Centre for Disease Prevention and Control (ECDC) promotes a point prevalence survey (PPS) of HAIs in European acute care hospitals. Through a retrospective analysis of 2012, 2015 and 2017 PPS of HAIs performed in a tertiary academic hospital in Italy, we developed a model to predict the risk of HAI. Methods: Following ECDC protocol we surveyed 1382 patients across three years. Bivariate logistic regression analyses were conducted to assess the relationship between HAI and several variables. Those statistically significant were included in a stepwise multiple regression model. The goodness of fit of the latter model was assessed with the Hosmer-Lemeshow test, ultimately constructing a probability curve to estimate the risk of developing HAIs. Results: Three variables resulted statistically significant in the stepwise logistic regression model: length of stay (OR 1.03; 95% CI: 1.02-1.05), devices breaking the skin (i.e. peripheral or central vascular catheter, OR 4.38; 95% CI: 1.52-12.63), urinary catheter (OR 4.71; 95% CI: 2.78-7.98). Conclusion: PPSs are a convenient and reliable source of data to develop HAIs prediction models. The differences found between our results and previously published studies suggest the need of developing hospital-specific databases and predictive models for HAIs.

COVID-19: opinions and behavior of Italian general population during the first epidemic phase.

BACKGROUND AND AIM: On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey. RESULTS: A study sample consisting of 4116 Italian individuals of both sexes was enrolled. High levels of risk perception, low perception of self-efficacy and low levels of knowledge scores (24.55 ± 5.76 SD) were obtained indicating the need for continuous population monitoring as well as further communication strategies carried out at institution levels. CONCLUSION: The results of the present study could help public health authorities in carrying out informative campaigns for general population and could be an important tool in evaluating public knowledge and misperceptions during the management of the COVID-19. (www.actabiomedica.it).

How to Improve the Drafting of Health Profiles.

Delineating patients' health profiles is essential to allow for a proper comparison between medical care and its results in patients with comorbidities. The aim of this work was to evaluate the concordance of health profiles outlined by ward doctors and by epidemiologists and the effectiveness of training interventions in improving the concordance. Between 2018 and 2021, we analyzed the concordance between the health profiles outlined by ward doctors in a private hospital and those outlined by epidemiologists on the same patients' medical records. The checks were repeated after training interventions. The agreement test (Cohen's kappa) was used for comparisons through STATA. The initial concordance was poor for most categories. After our project, the concordance improved for all categories of CIRS. Subsequently, we noted a decline in concordance between ward doctors and epidemiologists for CIRS, so a new training intervention was needed to improve the CIRS profile again. Initially, we found a low concordance, which increased significantly after the training interventions, proving its effectiveness.

Game of Mirrors: Health Profiles in Patient and Physician Perceptions.

The relationship between general practitioners and patients is privileged. The aim of this study was to assess the concordance between the health profile perceived by the patient and the one described by the doctor. We conducted a cross-sectional study between 2019-2020. Patients completed the 5d-5L (EQ-p) and clinicians completed it "from the patient's perspective" (EQ-d), also consulting the clinical diary. Statistical analysis was performed using Stata 14 (Cohen's kappa; Fisher's exact test). The sample consisted of 423 patients. The mean age was 56.7 ± 19.2. There were significant differences by gender in usual activities, pain, and anxiety/depression (74.6% of men had no limitation in usual activities versus 64.5% of women (p < 0.01), 53.9% of men had no pain versus 38.5% of women (p < 0.01), and 60.3% of men had no anxiety/depression versus 38.5% of women (p < 0.01)). Physicians did not detect these differences. The concordance between EQ-p and EQ-d was substantial for mobility (k = 0.62; p < 0.01), moderate for self-care (k = 0.48; p < 0.01) and usual activities (k = 0.50; p < 0.01). Concordance was fair for pain/discomfort (k = 0.32; p < 0.01), anxiety/depression (k = 0.38; p < 0.01), and EQ Index (k = 0.21; p < 0.01). There was greater agreement for "objective "dimensions (mobility, self-care, and usual activities). A good doctor, to be considered as such, must try to put himself in the "patient's pajamas" to feel his feelings and be on the same wavelength.

Complete Genome Sequences of Mycobacterium chimaera Strains 850 and 852, Isolated from Heater-Cooler Unit Water.

The whole-genome sequences of Mycobacterium chimaera strains 850 and 852, which were isolated from two different water samples obtained from a heater-cooler unit at Siena University Hospital (Italy), were determined by combining Nanopore and Illumina technologies. Genomes of both strains 850 and 852 consist of a circular chromosome and five plasmids, with sizes of 6,275,686 bp and 6,453,144 bp, respectively.

The seroprevalence of the hepatitis B virus in Italian medical students after 3 decades since the introduction of universal vaccination.

OBJECTIVES: Since 1991 hepatitis B vaccination has been mandatory for all newborns in Italy. The aim of the study was to verify the long-term seroprevalence and the efficacy of hepatitis B vaccination in medical students of the University of Siena. MATERIAL AND METHODS: A cross-sectional observational study was conducted on a population of 850 medical students of the University of Siena (322 males and 528 females, mean age: 23 years) by obtaining from the medical reports the serological analysis data for the total anti-hepatitis B antibodies (HBsAb) and information on hepatitis B vaccination (number of vaccine doses, age at the first vaccination, time since the final vaccination dose, country of origin). Raw odds ratios (ORs) and 95% confidence intervals (CIs) were initially calculated to evaluate the association between 2 variables. The adjusted ORs were then calculated using a multivariate logistic regression model to study the association between the variables and the possible confounding factors. RESULTS: Overall, 593 students (69.76%) were immunized against hepatitis B, while 257 (30.24%) had HBsAb antibody titer <10 mIU/ml. From the OR calculation, an inverse correlation emerged between seropositivity to hepatitis B and age, and between seropositivity to hepatitis B and the age at the first vaccination dose. There was also a correlation between seropositivity and the number of vaccination doses received. By performing the multivariate logistic analysis, correlations with these variables were confirmed. CONCLUSIONS: A significant part of the studied population was not immunized against hepatitis B virus, despite the fact that vaccination had been carried out as prescribed by law. The results of the study reaffirm the importance of health surveillance in subjects at biological risk such as medical students. Int J Occup Med Environ Health. 2022;35(1):75-80.

Bacterial lysates (OM-85 BV): a cost-effective proposal in order to contrast antibiotic resistance.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is one of the most frequent pathologies in which antibiotics are used because 50% of the exacerbations are attributable to a bacterial infection. The aims of our study were: i) to perform a meta-analysis on the efficacy of the bacterial lysate OM-85 BV in preventing acute exacerbations in patients with COPD; ii) to evaluate whether this preventive treatment can lead to significant savings for the National Health Service (NHS). METHODS: A systematic research was conducted in the electronic database MEDLINE (PubMed) in June 2017-July 2020, collecting evidences without time restrictions. Only randomized controlled trials (RCTs) were included. The keywords used were "OM 85 BV AND chronic bronchitis" and "OM 85 BV AND COPD". A cost-effectiveness analysis (CEA) was performed considering the costs for a treatment with OM-8BV, the costs for the treatment of an acute exacerbation and the number of prevented exacerbations. RESULTS: 59 publications were found, but the meta-analysis was conducted on 13 studies that met the inclusion criteria. OM-85 BV is responsible of a statistically significant reduction in the mean number of COPD exacerbations (p < 0.01; WMD = -0.86; CI 95%: -1.38, -0.34) and in the days of antibiotic therapy (p < 0.01; WMD = -9.49; CI 95%: -11.93, -7.05). The cost-effectiveness ratio with a negative value is in favor to treatment. CONCLUSIONS: OM-85 BV is effective in reducing exacerbations, and could lead to significant savings for the NHS. Moreover, reducing the number of exacerbations it could avoid an over-use of antibiotics and the consequent antibiotic resistance.

Inter-Regional Hospital Patients' Mobility in Italy.

BACKGROUND: The federalization of the Italian National Health Service (NHS) gave administrative, financial, and managerial independence to regions. They are in reciprocal competition according to the "quasi-market" model. A network of independent providers replaced the state monopoly. The NHS, based on the Beveridge model in which citizens are free to choose their place of treatment, was consolidated. The aim of our research was to analyze the fulfillment of need for hospital services on site and patients' migration to hospitals of other regions. MATERIAL AND METHODS: We analyzed data from 2013 to 2017 of Hospital Discharge Cards (HDCs) provided by the Ministry of Health. The subjects of the analysis (catchment areas) were the hospital networks of every Italian region. The study of flows was developed through Internal Demand Satisfaction, Attraction, Escape, Attraction, Absorption, and Escape Production indexes. Graphic representations were produced using Gandy's Nomogram and Qgis software. RESULTS: In the studied period, the mean number of mobility admission was 678.659 ± 3.388, with an increase of 0.90%; in particular, the trend for ordinary regime increased 1.17%. Regions of central/northern Italy have attracted more than 60% of the escapes of the southern ones. Gandy's Nomogram showed that only nine regions had optimal public hospital planning (Lombardy, Autonomous Province of Bolzano, Veneto, Friuli V.G., Emilia-Romagna, Tuscany, Umbria, Latium and Molise). CONCLUSION: The central/northern regions appear more able to meet the care needs of their citizens and to attract patients than the southern ones.

An Emerging Innovative UV Disinfection Technology (Part II): Virucide Activity on SARS-CoV-2.

The coronavirus SARS-CoV-2 pandemic has become a global health burden. Surface sanitation is one of the key points to reduce the risk of transmission both in healthcare and other public spaces. UVC light is already used in hospital and laboratory infection control, and some recent studies have shown its effectiveness on SARS-CoV-2. An innovative UV chip technology, described in Part I of this study, has recently appeared able to overcome the limits of old lamps and is proposed as a valid alternative to LEDs. This study was designed to test the virucidal activity on SARS-CoV-2 of a device based on the new UV chip technology. Via an initial concentration of virus suspension of 107.2 TCID50/mL, the tests revealed a viral charge reduction of more than 99.9% after 3 min; the maximum detectable attenuation value of Log10 = 5.7 was measured at 10 min of UV exposure.

Short-term treatment effects produced by rapid maxillary expansion evaluated with computed tomography: A systematic review with meta-analysis.

OBJECTIVE: To identify the available evidence on the effects of rapid maxillary expansion (RME) with three-dimensional imaging and provide meta-analytic data from studies assessing the outcomes using computed tomography. METHODS: Eleven electronic databases were searched, and prospective case series were selected. Two authors screened all titles and abstracts and assessed full texts of the remaining articles. Seventeen case series were included in the quantitative synthesis. Seven outcomes were investigated: nasal cavity width, maxillary basal bone width, alveolar buccal crest width, alveolar palatal crest width, inter-molar crown width, inter-molar root apex width, and buccopalatal molar inclination. The outcomes were investigated at two-time points: postexpansion (2-6 weeks) and post-retention (4-8 months). Mean differences and 95% confidence intervals were used to summarize and combine the data. RESULTS: All the investigated outcomes showed significant differences postexpansion (maxillary basal bone width, +2.46 mm; nasal cavity width, +1.95 mm; alveolar buccal crest width, +3.90 mm; alveolar palatal crest width, +3.09 mm; intermolar crown width, +5.69 mm; inter-molar root apex width, +2.85 mm; and dental tipping, +3.75°) and post-retention (maxillary basal bone width, +2.21 mm; nasal cavity width, +1.55 mm; alveolar buccal crest width, +3.57 mm; alveolar palatal crest width, +3.32 mm; inter-molar crown width, +5.43 mm; inter-molar root apex width, +4.75 mm; and dental tipping, 2.22°) compared to pre-expansion. CONCLUSIONS: After RME, skeletal expansion of the nasomaxillary complex was greater in most caudal structures. Maxillary basal bone showed 10% post-retention relapse. During retention period, uprighting of maxillary molars occurred.

A mobile device reducing airborne particulate can improve air quality.

Surgical site infections are the second major cause of hospital acquired infections, accounting for a large part of overall annual medical costs. Airborne particulate is known to be a potential carrier of pathogenic bacteria. We assessed a mobile air particle filter unit for improvement of air quality in an operating room (OR). A new mobile air decontamination and recirculation unit, equipped with a crystalline ultraviolet C (Illuvia® 500 UV) reactor and a HEPA filter, was tested in an OR. Airborne particulate was monitored in four consecutive phases: I) device OFF and OR at rest; II) device OFF and OR in operation; III) device ON and OR in operation; IV) device OFF and OR in operation. We used a particle counter to measure airborne particles of different sizes: ≥0.3, ≥0.5, ≥1, ≥3, ≥5, >10 µm. Activation of the device (phases III) produced a significant reduction (p < 0.05) in airborne particulate of all sizes. Switching the device OFF (phase IV) led to a statistically significant increase (p < 0.05) in the number of particles of most sizes: ≥0.3, ≥0.5, ≥1, ≥3 µm. The device significantly reduced airborne particulate in the OR, improving air quality and possibly lowering the probability of surgical site infections.