Frequency and classification of drug-related incidents in an infectious disease ward of a high-complexity hospital

Infectious Disease Hospitalizations: United States, 2001 to 2014

ObjectiveAlthough adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal...

The object of the study was represented by healthcare workers from infectious disease and multidisciplinary hospitals repurposed to treat COVID-19 patients. The aim of the study was to assess subjective perception of discomfort associated with prolonged use of personal protective equipment (PPE) and to identify differences in adaptation to such working conditions between healthcare staff in infectious disease and multidisciplinary hospitals during the COVID-19 pandemic. A survey was conducted among healthcare workers, including questions on daily duration of PPE use (medical masks/respirators, protective goggles, coveralls) and the presence of symptoms indicating adverse effects of prolonged PPE using. Changes in working conditions during the COVID-19 pandemic led to a significant increase in the proportion of healthcare workers regularly using PPE as well as a substantial rise in duration of its use. Prolonged PPE use during the pandemic resulted in an increased frequency of complaints related to PPE in both hospital types. Higher prevalence of complaints associated with PPE use was observed in the multidisciplinary hospital, both during routine and repurposing periods, as well as a greater change in the frequency of systemic physiological disorders while wearing respiratory PPE (difficulty breathing, sensation of shortness of breath, dizziness) during the pandemic in the multidisciplinary hospital compared to the infectious disease hospital. The identified inter-hospital differences likely reflect greater adaptability among staff in infectious disease hospitals to prolonged PPE use attributed to stringent infection control protocols and the availability of well-tested algorithms for working in routine daily practice. These disparities in preparedness and adaptation of healthcare workers to PPE use in repurposed hospitals highlight the need for expanded implementation of occupational health risk management measures, emphasize the importance of optimizing PPE design, improving selection and usage protocols, introducing training programs on rational PPE use, and conducting regular health screenings for PPE-related adverse effects among healthcare workers.

American Indians and Alaska Natives (AI/AN) adults > or = 65 years of age (older adults) have the second highest age group-specific infectious disease (ID) hospitalization rate. To assess morbidity and disparities of IDs for older AI/AN adults, this study examined the epidemiology of overall and specific infectious disease hospitalizations among older AI/AN adults. ID hospitalization data for older AI/AN adults were analyzed by using Indian Health Service hospital discharge data for 1990 through 2002 and comparing it with published findings for the general U.S. population of older adults. ID hospitalizations accounted for 23% of all hospitalizations among older AI/AN adults. The average annual ID hospitalization rate increased 5% for 1990-1992 to 2000-2002; however, the rate increased more than 20% in the Alaska and the Southwest regions. The rate for older AI/AN adults living in the Southwest region was greater than that for the older U.S. adult population. For 2000-2002, lower respiratory tract infections accounted for almost half of all ID hospitalizations followed by kidney, urinary tract, and bladder infections, and cellulitis. The ID hospitalization rate increased among older AI/AN adults living in the Southwest and Alaska regions, and the rate for the older AI/AN adults living in the Southwest region was higher than that for the U.S. general population. Prevention measures should focus on ways to reduce ID hospitalizations among older AI/AN adults, particularly those living in the Southwest and Alaska regions.

To describe total and average hospital charges associated with infectious disease (ID) hospitalizations and specific ID categories and to estimate ID hospitalization rates in adults aged 65 and older in the United States from 1998 through 2004. Retrospective analysis of hospital discharge data obtained from the Nationwide Inpatient Sample for 1998 through 2004. United States. Older adults hospitalized in the United States from 1998 through 2004. Hospital charges and hospitalization rates for IDs described according to year, age group, sex, U.S. Census region, and ID category. Charges for non-ID hospitalizations were also described. Hospital charges were adjusted for inflation. From 1998 through 2004, total charges for ID hospitalizations exceeded $261 billion and accounted for 13% of all hospital charges for older adults. Total charges for ID hospitalizations increased from $31.4 billion in 1998 to $45.7 billion in 2004. The average annual ID hospital charge was lower than the average annual non-ID hospital charge during the study period ($21,342 vs $22,787, P<.001). The average annual rate for ID hospitalizations was 503 per 10,000 older adults, which remained stable during the study period. The total charges for ID hospitalizations and for all hospitalizations in older adults in the United States increased 45% and nearly 40%, respectively, during the 7-year study period, whereas the population of older adults grew by only 5%. Sustained increases of such magnitude will have major implications for the U.S. healthcare system as it prepares for the more than doubling of the older U.S. adult population during the first 30 years of this century.

Aim: This study aims to evaluate the prevalence, severity, and clinical impact of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in elderly patients receiving polypharmacy (≥5 medications). It also seeks to identify the most commonly implicated drug classes and assess the association between polypharmacy, comorbidities, and medication-related complications. Materials and Methods: A prospective observational study was conducted at a tertiary care hospital, including 100 elderly patients (≥65 years) on multiple medications. Data on demographics, comorbidities, medication history, ADRs, and DDIs were collected using a structured format. ADRs were assessed for causality (Naranjo Scale), severity (Hartwig and Siegel Scale), and preventability (Schumock and Thornton criteria). DDIs were identified and classified based on their clinical significance using standard drug interaction databases. Statistical analysis was performed using SPSS 25.0, with significance set at p &lt; 0.05. Results: The mean age of the patients was 72.5 ± 5.8 years, with 55% males and 45% females. The average number of comorbidities was 3.2 ± 1.5, with hypertension (65%), diabetes mellitus (50%), and ischemic heart disease (25%) being the most prevalent. Polypharmacy was observed in all patients, with 40% taking 5-6 medications, 30% on 7-8, and 10% on more than 10 drugs. ADRs were recorded in 50% of patients, with 40% classified as probable and 20% as definite ADRs. Severe ADRs were noted in 20% of cases (p=0.01). Moderate-to-severe DDIs were identified in 75% of patients, leading to hospitalization in 15% of cases (p=0.02) and medication changes in 40% (p=0.03). The most implicated drug classes in ADRs and DDIs included antihypertensives (30% ADRs, 25% DDIs), antidiabetics (25% ADRs, 20% DDIs), NSAIDs (15% ADRs, 30% DDIs), and anticoagulants (20% ADRs, 35% DDIs, p=0.005). Conclusion: This study highlights the high prevalence of ADRs and DDIs in elderly polypharmacy patients, with moderate-to-severe ADRs affecting 50% of patients and hospitalization occurring in 15% of DDI cases. Polypharmacy significantly increased the risk of ADRs and DDIs, particularly with high-risk medications such as antihypertensives, anticoagulants, NSAIDs, and antidiabetics. The findings emphasize the need for regular medication reviews, deprescribing strategies, and improved pharmacovigilance to minimize medication-related harm in geriatric patients

To evaluate the quality of life (QoL) of patients with Chagas disease (CD) and the association between QoL domains and several clinical, socioeconomic and lifestyle characteristics of this population. Cross-sectional observational study conducted from March 2014 to March 2017 including a total of 361 outpatients followed at Evandro Chagas National Institute of Infectious Disease, Brazil. QoL was assessed using the Portuguese shorter version of the original WHO Quality of Life questionnaire (WHOQOL-BREF). Information about clinical CD presentation, presence of comorbidities, functional class, previous benznidazole treatment, socioeconomic profile and lifestyle was also obtained. Environment and physical domains presented the worst QoL scores, while the social relationship domain presented the highest score. Multivariate regression analysis demonstrated that variables independently associated with QoL were functional class, sex, clinical presentation of CD, sleep duration, schooling, physical activity level, smoking, income per capita and residents by domicile. The low socioeconomic status and the physical limitations imposed by the disease presented an important impact on the QoL reduction among CD patients, especially on environment and physical domains. Strategies to improve QoL among CD patients should be tailored and consider many different variables to maximise improvements not only of patients' physical but also of their mental health.

Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons.

To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year ($US59 600/year) [ 1999 values]. Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.

BackgroundAntimicrobial stewardship programs (ASPs) are now a requirement for many hospitals, but a large proportion of US hospitals lack an on-site Infectious Disease (ID) specialist. We sought to compare the processes and outcomes of ASPs at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist.MethodsThis retrospective cohort included all acute-care patients in VHA hospitals admitted during 2016, or 2 years after a VHA mandate for hospital-based ASPs. Data from a mandatory nationwide survey were used to identify hospitals that self-reported the absence of an on-site ID specialist, including an ID physician or ID pharmacist, in 2016. Antimicrobial use was quantified at the hospital-level as days-of-therapy (DOTs) per 1,000 days present and categorized based on National Healthcare Safety Network definitions. A facility-level negative binomial regression model with risk adjustments made for aggregated case-mix and facility-level factors was used to determine the association between the presence of an on-site ID specialist and antimicrobial use.ResultsEighteen of 122 (14.8%) hospitals lacked an on-site ID specialist. Non-ID hospitals had fewer admissions per month than ID sites (mean 107.3 vs. 425.4, P < 0.01). An ASP policy and an ASP pharmacy champion were present at ≥90% of hospitals with and without an ID specialist. Core ASP strategies were frequently used in both ID and non-ID sites, including prior authorization (90.4% vs. 83.3%, P = 0.41) and prospective audit-and-feedback (76.9% vs. 66.7%, P = 0.38). Broad-spectrum antibacterial use (263.9 vs. 317.6 DOTs per 1,000 days-present, P = 0.01) but not total antimicrobial use (600.8 vs. 634.3 DOTs per 1,000 days-present, P = 0.34) was lower at ID vs. non-ID hospitals. After facility-level risk-adjustment, broad-spectrum antibacterial use (OR = 0.81, 95% CI 0.69–0.94) but not total antimicrobial use (OR = 0.92, 95% CI 0.70–1.21) was lower at ID hospitals.ConclusionAn on-site ID specialist was not associated with greater use of core ASP strategies, but the presence of an on-site ID specialist was associated with less frequent prescribing of broad-spectrum antibacterial agents. An on-site ID specialist may be an important part of an effective hospital-based ASP.DisclosuresAll authors: No reported disclosures.

BackgroundThe expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions. A computational method that provides prospective predictions of potential DDI-induced ADRs will help to identify and mitigate these adverse health effects.MethodWe hypothesize that drug-protein interactions can be used as independent variables in predicting ADRs. We constructed drug pair-protein interaction profiles for ~800 drugs using drug-protein interaction information in the public domain. We then constructed statistical models to score drug pairs for their potential to induce ADRs based on drug pair-protein interaction profiles.ResultsWe used extensive clinical database information to construct categorical prediction models for drug pairs that are likely to induce ADRs via synergistic DDIs and showed that model performance deteriorated only slightly, with a moderate amount of false positives and false negatives in the training samples, as evaluated by our cross-validation analysis. The cross validation calculations showed an average prediction accuracy of 89% across 1,096 ADR models that captured the deleterious effects of synergistic DDIs. Because the models rely on drug-protein interactions, we made predictions for pairwise combinations of 764 drugs that are currently on the market and for which drug-protein interaction information is available. These predictions are publicly accessible at http://avoid-db.bhsai.org. We used the predictive models to analyze broader aspects of DDI-induced ADRs, showing that ~10% of all combinations have the potential to induce ADRs via DDIs. This allowed us to identify potential DDI-induced ADRs not yet clinically reported. The ability of the models to quantify adverse effects between drug classes also suggests that we may be able to select drug combinations that minimize the risk of ADRs.ConclusionAlmost all information on DDI-induced ADRs is generated after drug approval. This situation poses significant health risks for vulnerable patient populations with comorbidities. To help mitigate the risks, we developed a robust probabilistic approach to prospectively predict DDI-induced ADRs. Based on this approach, we developed prediction models for 1,096 ADRs and used them to predict the propensity of all pairwise combinations of nearly 800 drugs to be associated with these ADRs via DDIs. We made the predictions publicly available via internet access.

Background: Drug-drug interactions (DDIs) are an important cause of adverse drug reactions (ADRs). In literature most of studies focus only on potential DDIs, while detailed data on serious ADRs associated with DDIs are limited. Our aim is to identify and characterize serious ADRs caused by DDIs using a spontaneous reporting database. Methods: All serious ADR reports, not related to vaccines and with a “definite”, “probable” or “possible” causality assessment, inserted into the National Pharmacovigilance database from Veneto Region (January 1, 2015 to May 31, 2020) were analyzed. A list of drug pairs was created by selecting the reports containing at least two suspected or concomitant drugs. We verified which drug pairs potentially interacted according to the online version of DRUGDEX® system. For each potential DDI we controlled whether the ADR description in the report corresponded to the interaction effect as described in Micromedex. A detailed characterization of all serious reports containing an occurring DDI was performed. Results: In the study period a total of 31,604 reports of suspected ADRs from the Veneto Region were identified, of which 2,195 serious reports (6.9% of all ADR reports) containing at least two suspected or concomitant drugs were analyzed. We identified 1,208 ADR reports with at least one potential DDI (55.0% of 2,195) and 381 reports (17.4% of 2,195 reports) with an occurring ADR associated with a DDI. The median age of patients and the number of contraindicated or major DDIs were significantly higher in reports with an occurring DDI. Warfarin was the most frequently reported interacting drug and the most common ADRs were gastrointestinal or cerebral hemorrhagic events. The proton pump inhibitors/warfarin, followed by platelet aggregation inhibitors/warfarin were the drug-drug combinations most frequently involved in ADRs caused by DDIs. The highest proportion of fatal reports was observed with platelet aggregation inhibitors/warfarin and antidepressants/warfarin. Conclusion: Our findings showed that about one-third of patients exposed to a potential DDI actually experienced a serious ADR. Furthermore, our study confirms that a spontaneous reporting database could be a valuable resource for identifying and characterizing ADRs caused by DDIs and the drugs leading to serious ADRs and deaths.

Chagas disease is caused by infection with Trypanosoma cruzi. In adults, treatment with benznidazole is associated with a high incidence of adverse drug reactions (ADRs). However, in infants and children, treatment with benznidazole seems associated with a lower incidence and decreased severity of ADRs, but these effects have not been clearly characterized. We aimed to describe ADRs observed in infants and children treated with benznidazole. We conducted a prospective cohort study of infants and children in Argentina with Chagas disease treated with benznidazole. A total of 107 infants and children diagnosed with asymptomatic Chagas disease (mean age: 6.9 years) were enrolled in the study. Sixty-two events (in 44 children) were considered benznidazole related. Mean ADR duration was 8.2 days. ADRs were mild (80.6%), moderate (16%), or severe (3.2%). Most (77.3%) ADRs were in children older than 7 years. Skin was the organ with the highest incidence of ADRs (21%), followed by the central nervous system (9%) and the gastrointestinal tract (8.5%). Also, the ADR rate was lower in infants and toddlers compared with older children (18% vs 53%) (P < .001). Treatment with benznidazole was well tolerated in children. Most ADRs were mild and did not require treatment suspension. A strong association was observed between ADR incidence and patient age, and most ADRs occurred in children older than 7 years. We believe that anxiety over potential severe ADRs in children with Chagas disease is not justified and should not be an obstacle to using benznidazole.

Research assessing the changing epidemiology of infectious diseases in China after the implementation of new healthcare reform in 2009 was scarce. We aimed to get the latest trends and disparities of nationalnotifiable infectious diseases by age, sex, province, and season in China from 2010 to 2019. The number of incident cases and deaths, incidence rate, and mortality of 44 national notifiable infectious diseases by sex, age groups, and provincial regions from 2010 to 2019 were extracted from the China Information System for Disease Control and Prevention and official reports and divided into six kinds of infectious diseases by transmission routes and three classes (A-C) in this descriptive study. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends of incidence and mortality rate. We calculated the concentration index to measure economic-related inequality. Segmented interrupted time-series analysis was used to estimate the impact of the COVID-19 pandemic on the epidemic of notifiable infectious diseases. The trend of incidence rate on six kinds of infectious diseases by transmission routes was stable, while only mortality of sexual, blood-borne, and mother-to-child-borne infectious diseases increased from 0.6466 per 100 000 population in 2010 to 1.5499 per 100 000 population in 2019 by 8.76% per year (95% confidence interval [CI]: 6.88-10.68). There was a decreasing trend of incidence rate on Class-A infectious diseases (EAPC = -16.30%; 95%CI: -27.93 to -2.79) and Class-B infectious diseases (EAPC = -1.05%; 95%CI: -1.56 to -0.54), while an increasing trend on Class-C infectious diseases (EAPC = 6.22%; 95%CI: 2.13-10.48). For mortality, there was a decreasing trend on Class-C infectious diseases (EAPC = -14.76%; 95%CI: -23.46 to -5.07), and an increasing trend on Class-B infectious diseases (EAPC = 4.56%; 95%CI: 2.44-6.72). In 2019, the infectious diseases with the highest incidence rate and mortality were respiratory diseases (340.95 per 100 000 population), and sexual, blood-borne, and mother-to-child-borne infectious diseases (1.5459 per 100 000 population), respectively. The greatest increasing trend of incidence rate was observed in seasonal influenza, from 4.83 per 100 000 population in 2010 to 253.36 per 100 000 population in 2019 by 45.16% per year (95%CI: 29.81-62.33), especially among females and children aged 0-4 years old. The top disease with the highest mortality was still AIDs, which had the highest average yearly mortality in 24 provinces from 2010 to 2019, and its incidence rate (EAPC = 14.99%; 95%CI: 8.75-21.59) and mortality (EAPC = 9.65; 95%CI: 7.71-11.63) both increased from 2010 to 2019, especially among people aged 44-59 years old and 60 or older. Male incidence rate and mortality were higher than females each year from 2010 to 2018 on 29 and 10 infectious diseases, respectively. Additionally, sex differences in the incidence and mortality of AIDS were becoming larger. The curve lay above the equality line, with the negative value of the concentration index, which indicated that economic-related health disparities exist in the distribution of incidence rate and mortality of respiratory diseases (incidence rate: the concentration index = -0.063, p < 0.0001; mortality: the concentration index = -0.131, p < 0.001), sexual, blood-borne, and mother-to-child-borne infectious diseases (incidence rate: the concentration index = -0.039, p = 0.0192; mortality: the concentration index = -0.207, p < 0.0001), and the inequality disadvantageous to the poor (pro-rich). Respiratory diseases (Dec-Jan), intestinal diseases (May-Jul), zoonotic infectious diseases (Mar-Jul), and vector-borne infectious diseases (Sep-Oct) had distinct seasonal epidemic patterns. In addition, segmented interrupted time-series analyses showed that, after adjusting for potential seasonality, autocorrelation, GDP per capita, number of primary medical institutions, and other factors, there was no significant impact of COVID-19 epidemic on the monthly incidence rate of six kinds of infectious diseases by transmission routes from 2018 to 2020 (all p > 0.05). The incidence rates of six kinds of infectious diseases were stable in the past decade, and incidence rates of Class-A and Class-B infectious diseases were decreasingbecause of comprehensive prevention and control measures and a strengthened health system after the implementation of the new healthcare reform in China since2009. However, age, gender, regional, and economic disparities were still observed. Concerted efforts are needed to reduce the impact of seasonal influenza (especially among children aged 0-4 years old) and the mortality of AIDs (especially among people aged 44-59 years old and 60 or older). More attention should be paid to the disparities in the burden of infectious diseases.

The object of the study was represented by healthcare workers from infectious disease and multidisciplinary hospitals repurposed to treat COVID-19 patients. The aim of the study was to assess subjective perception of discomfort associated with prolonged use of personal protective equipment (PPE) and to identify differences in adaptation to such working conditions between healthcare staff in infectious disease and multidisciplinary hospitals during the COVID-19 pandemic. A survey was conducted among healthcare workers, including questions on daily duration of PPE use (medical masks/respirators, protective goggles, coveralls) and the presence of symptoms indicating adverse effects of prolonged PPE using. Changes in working conditions during the COVID-19 pandemic led to a significant increase in the proportion of healthcare workers regularly using PPE as well as a substantial rise in duration of its use. Prolonged PPE use during the pandemic resulted in an increased frequency of complaints related to PPE in both hospital types. Higher prevalence of complaints associated with PPE use was observed in the multidisciplinary hospital, both during routine and repurposing periods, as well as a greater change in the frequency of systemic physiological disorders while wearing respiratory PPE (difficulty breathing, sensation of shortness of breath, dizziness) during the pandemic in the multidisciplinary hospital compared to the infectious disease hospital. The identified inter-hospital differences likely reflect greater adaptability among staff in infectious disease hospitals to prolonged PPE use attributed to stringent infection control protocols and the availability of well-tested algorithms for working in routine daily practice. These disparities in preparedness and adaptation of healthcare workers to PPE use in repurposed hospitals highlight the need for expanded implementation of occupational health risk management measures, emphasize the importance of optimizing PPE design, improving selection and usage protocols, introducing training programs on rational PPE use, and conducting regular health screenings for PPE-related adverse effects among healthcare workers.