Distribution of Chlamydia trachomatis ompA-genotypes over three decades in Portugal.

OBJECTIVES: Chlamydia trachomatis is classified into 15 major genotypes, A to L3, based on the diversity of ompA gene. Here, we evaluated and characterised the distribution and diversity of ompA-genotypes over 32 years (1990-2021) in Portugal. METHODS: The collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections includes 5824 C. trachomatis-positive samples that were successfully ompA-genotyped between 1990 and 2021. An in-depth analysis of ompA-genotypes distribution across the years, as well as by biological sex, age and anatomical site of infection was performed. RESULTS: ompA-genotype E was consistently the most frequently detected across the years, with a median frequency of 34.6%, followed by D/Da (17.6%), F (14.3%) and G (10.7%). The prevalence of lymphogranuloma venereum (LGV) genotypes (mostly L2, 62.0%, followed by L2b, 32.1%) increased since 2016, reaching the highest value in 2019 (20.9%). LGV, G and Da genotypes were associated with biological sex, specifically with being male, and were the most frequent among anorectal specimens (37.7%, 19.4% and 17.7%, respectively). Notably, LGV ompA-genotypes represented 38.9% of the male anorectal specimens since 2016, and were also detected among oropharynx and urogenital samples. ompA-genotype E was the most frequently detected at the oropharynx (28.6%) and urogenital (33.9%) sites during the study period, followed by D/Da (17.4%) and F (16.0%) in the urogenital specimens, and by G (26.1%) and D/Da (25.7%) in oropharynx specimens. Our data also highlight the emergence of the recombinant L2b/D-Da strain since 2017 (representing between 2.0% and 15.5% of LGV cases per year) and the non-negligible detection of ompA-genotype B in urogenital and anorectal specimens. CONCLUSIONS: This study provides a comprehensive landscape of C. trachomatis molecular surveillance in Portugal, highlighting the continued relevance of ompA-genotyping as a complement to rapid LGV-specific detection tests. It also contributes to a deeper understanding of C. trachomatis epidemiology, diversity and pathogenicity.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

Learning curve for minimal invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures.

PURPOSE: The benefits of the minimally invasive approach for performing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) have been described previously, associating an early recovery with similar oncologic outcomes in patients with limited peritoneal carcinomatosis. Currently, no studies are focusing on the learning curve for this emerging procedure. This study aimed to evaluate the L-CRS + HIPEC learning curve and its knock-on effect on the perioperative outcomes. METHODS: We identified all consecutive unselected patients who underwent L-CRS + HIPEC by a single surgeon between April 2016 and January 2022 (n = 51). Patients who underwent risk-reducing CRS + HIPEC (PCI = 0) or initial conversion due to an intraoperative PCI > 10 were excluded from the final analysis. To evaluate the learning curve, perioperative data were analysed using the cumulative sum (CUSUM) analysis. RESULTS: Twenty-six patients were included in the final analysis. Major morbidity occurred in one patient (3.8%). The difficulty of the L-CRS + HIPEC procedures was categorised as low in 23.1% (n = 6), intermediate in 19.2% (n = 5), and advanced in 57.7% (n = 15). The mean length of hospital stay was 5.4 ± 1.5 days. No patient had a conversion to open surgery. The learning curve was divided into two distinct phases: the learning phase (1-14) and the consolidation phase (15-26). A significant decrease in the operative time (375 ± 103.1 vs 239.2 ± 63.6 min) was observed with no differences in complexity, the number of peritonectomy procedures, or morbidity. CONCLUSION: L-CRS + HIPEC is a complex procedure that must be performed in a high-volume and experienced oncologic unit, requiring a learning curve to achieve the consolidation condition, which could be established after 14 procedures.

CHRONOFALLS: A multicentre nurse-led intervention in the chronoprevention of in-hospital falls in adults.

BACKGROUND: Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. METHODS: A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. RESULTS: A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p < 0,001). According to the interrupted series analysis, considering the influence of the COVID-19 pandemic, a reduction in falls of 2.96% (95% CI 1.70%-4.17%) was observed. The concepts of falls, the COVID-19 pandemic and the causes of non-registration have emerged as categories for qualitative analysis. CONCLUSIONS: A multicentric nurse-led program based on tailored organisational, educational and behavioural chronopreventive measures seems to lead to a reduction in the number of in-hospital falls. The findings of the present study, highlighting the implementation of chronopreventive measures, can serve as a basis for future health policies. TRIAL REGISTRATION: The project was registered on the Clinical Trials Registry NCT04367298 (29/04/2020).

Formal and Informal Services Used by Women Who Suffer Intimate Partner Violence in Spain.

Intimate partner violence (IPV) is an important public health problem. Female victims of IPV do not always use the institutional resources available to them. We conducted a cross-sectional study using data from the Spanish 2014 Macro-Survey on Violence Against Women. The findings show that 15% of the survey participants suffered from IPV in the last year. The factors associated with a higher probability of suffering IPV are being of non-Spanish nationality, being a student, having a low-educational level, having no income, being the household head, and not having a current partner. Regarding the resources used by women subjected to IPV, almost half resorted to informal sources, such as female friends and/or their own mothers. The use of formal resources was low. Therefore, IPV continues to be a problem in Spain that seems to remain in the private domain. Consequently, it is necessary to increase the availability of and access to legal resources.

Clinical and Epidemiological Characterization of Lymphogranuloma Venereum in a Sexually Transmitted Diseases Clinic in Lisbon, 2001 to 2020.

ABSTRACT: Between 2001 and 2020, 54 LGV cases were diagnosed in a sexually transmitted disease clinic in Lisbon, most in men who have sex with men (87%), HIV negative (63%), from the anorectal mucosa (72.2%). Cases among heterosexuals were also identified (13%). Surveillance programs irrespective of sexual orientation and HIV status are needed to avoid the morbidity associated with LGV.

Global gene expression analysis of Streptococcus agalactiae at exponential growth phase.

A comparative overview of the global gene expression levels of S. agalactiae reference strain NEM316 at the exponential growth phase was done through RNA-sequencing. The expression levels of 47 genes potentially linked to virulence evidenced that: i) the major nuclease, GBS_RS03720/gbs0661, presented higher mean expression values than the remainder of DNase genes; ii) the genetic pilus island PI-2a genes presented higher mean expression values than PI-1 coding genes; and, iii) three virulence-associated genes ranked among the top-100 most expressed genes (GBS_RS07760, GBS_RS09445 and GBS_RS03485). Among this top-100, genes encoding proteins involved in "Translation, ribosomal structure and biogenesis" represented 46%. Curiously, genes with no assigned function were grouped in the category of highly expressed genes. As very little is known about the molecular mechanisms behind the release of DNases, preliminary assays were developed to understand whether direct DNA exposure would affect gene expression at the exponential growth phase. No differentially expressed genes were detected, indicating that follow-up studies are needed to disclose the complex molecular pathways (and stimuli) triggering the release of DNases. In general, our insights on the global expression levels of NEM316 at exponential growth phase with and without DNA exposure should open novel research lines to decipher S. agalactiae puzzling adaptation and virulence mechanisms, such as DNase production.

Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022.

Up to 27 May 2022, Portugal has detected 96 confirmed cases of monkeypox. We describe 27 confirmed cases (median age: 33 years (range: 22-51); all males), with an earliest symptom onset date of 29 April. Almost all cases (n = 25) live in the Lisbon and Tagus Valley health region. Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.

Impact of sound levels on physiological and consciousness state of cardiovascular patients.

BACKGROUND: Patients treated in intensive care units (ICUs) experience life-threatening medical conditions but some external factors in ICUs do not help or even adversely affect and complicate their evolution. Among others, such factors include noise pollution due to alarms and medical clinical equipment, as well as the activities of the health care personnel themselves. AIM: This study aimed to evaluate the influence of elevated sound levels on physiological variables and the consciousness state of patients treated in a cardiovascular area in an ICU. DESIGN: A longitudinal study with several observations was carried out during 1 month in the cardiovascular area of an ICU of a third-level hospital in southern Spain. METHODS: Sound levels were monitored in different work shifts and patients' physiological data and consciousness status were recorded. Generalized additive mixed models (GAMMs) were developed to detect the variability of the sound levels together with the vital parameters of the patients in the ICU. RESULTS: Thirty-eight patients were included. The mean sound level was 54.09 dBA. The GAMM sound levels analysis showed a significant increase in sound levels from 4:30 p.m. to 8:00 p.m. (1.83 dBA; P < .001) and 8:00 p.m. to 11:30 p.m. (3.06 dBA; P < .001). An increase in heart rate (3.66 bpm; P < .001), respiratory rate (2.62 rpm; P < .001) and the Glasgow Coma Scale (0.50 units; P = .002) was detected during the 4:30 p.m.-8:30 p.m. CONCLUSIONS: Elevated sound levels in cardiovascular ICUs seem to influence positively the physiological and consciousness status of patients. Given the importance of the findings for patient safety, future intervention studies are recommended. RELEVANCE TO CLINICAL PRACTICE: The finding of this study could translate into structural changes in ICU facilities, as well as the development of clinical practice guidelines that influence the behaviour of health care professionals.

Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance.

Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.

Chronoprevention in hospital falls of older people: protocol for a mixed-method study.

BACKGROUND: Accidental falls in hospitals are serious events concerning the safety of the patients. Recent studies demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. The aim of the study is to determine the effect of the application of a programme of preventive measures based on the temporal patterns of the risk factors on the hospital fall occurrence. METHODS: A mixed-method research design. The following three phases will be carried out: 1) Longitudinal prospective study in two parts: (a) audits and seminars of healthcare professionals focused on an effective and efficient hospital falls register. Multi-Component and Single Cosinor analyses will be performed to obtain the temporal patterns of hospital falls and their related variables and (b) implementation of a based-temporal patterns, multidimensional prevention programme. 2) Retrospective study of falls registered in institutional databases. 3) Qualitative study based on focus groups (physicians, nurses and nursing assistants). The study protocol was approved in 2018. DISCUSSION: With regard to the safety of patients, hospital falls are serious events. Recent studies have demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. It is imperative to study temporal patterns of hospital falls to effectively and comprehensively define the aetiology of falls and, therefore, design preventive strategies. A reduction of the number of in-hospital falls and related injuries is expected, as well as an improvement in the quality of life of patients. Considering temporal patterns and levels of mood and sleep of healthcare professionals will achieve an improvement in patient safety. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov ID: NCT04367298.

Cephalosporin-Resistant Neisseria gonorrhoeae Isolated in Portugal, 2019.

We report a multidrug-resistant Neisseria gonorrhoeae exhibiting resistance to ceftriaxone and cefixime, isolated in Portugal in 2019. Whole-genome sequencing was performed for typing and identification of genetic determinants of antimicrobial resistance. Because of its antimicrobial susceptibility profile, awareness should be raised for the circulation of this strain.

Fifteen years of a nationwide culture collection of Neisseria gonorrhoeae antimicrobial resistance in Portugal.

Neisseria gonorrhoeae antimicrobial resistance (AMR) and gonorrhea disease burden remain major public health concerns worldwide. To contribute to the supranational demands to monitor and manage the spread of antimicrobial-resistant N. gonorrhoeae, the Portuguese NIH promoted the creation of the National Laboratory Network for Neisseria gonorrhoeae Collection (PTGonoNet). The present study reports the N. gonorrhoeae major AMR trends observed from 2003 up to 2018. All isolates described in the present study constitute the opportunistic ongoing N. gonorrhoeae isolate collection supported by the National Reference Laboratory for Sexually Transmitted Infections of the Portuguese NIH, enrolling strains isolated in 35 different public and private laboratories. Minimum inhibitory concentrations were determined using E-tests for azithromycin, benzylpenicillin, cefixime, ceftriaxone, ciprofloxacin, gentamicin, spectinomycin and tetracycline. Molecular typing was determined using NG-MAST. AMR data of 2596 country-spread isolates show that 87.67% of all N. gonorrhoeae isolates presented decreased susceptibility to at least one antimicrobial. A continuous decreased susceptibility and resistance to penicillin, tetracycline and ciprofloxacin can be observed along the years. However, no decreased susceptibility to cephalosporins was observed until 2018, while for azithromycin, this was always low. The most common observed NG-MAST genogroups were G1407, G7445, G225, G2, and G1034. This study evidences the advantages of a nationwide collection of isolates and of centralized AMR testing to respond to supranational (EURO-GASP) requirements while providing unprecedented data on AMR in the context of 15 years of surveillance.

Severe trauma patients and nursing practice-associated infections.

AIMS: Our study examined factors influencing the development of healthcare-associated infections in the intensive care unit (ICU) of a tertiary hospital in southern Spain. BACKGROUND: Healthcare-associated infections are a frequent adverse event, significantly lengthening patient stays in the ICU. Nursing practice is a key factor in the infection control process. DESIGN: A retrospective longitudinal study with two observation periods (admission and discharge) was performed in an ICU of a tertiary hospital. METHODS: We analysed patient records for those admitted to this unit coded as CIE 800-959.9 from 2012 to 2016. Using binomial logistic regression analysis, we analysed factors associated with healthcare-associated infections. RESULTS: We analysed 375 records (men: 78.1%; average age: 46.63 years). Of these, 9.2% patients acquired a healthcare-associated infection during their stay. Nursing practice-related factors significantly associated with the development of infection were the number of days connected to mechanical ventilation and the number of days in the ICU. CONCLUSION: Healthcare-associated infections in patients with severe trauma admitted to the ICU are mainly associated with the management of invasive techniques. A multidisciplinary approach should focus on the review of action and care plans.

Association between Physical Activity, Food Consumption and Depressive Symptoms Among Young Adults in Spain: Findings of a National Survey.

Young adults have a significant prevalence of mental disorders, which could lead to dysfunctional quality of life. Records of 1,645 Spanish adolescents were examined and multiple logistic regressions were performed. Being a woman, being older and having a sedentary life were all associated with a higher psychological vulnerability, whereas a low frequency of fresh fruit and bread/cereals consumption, as well as regular intense physical activity, were considered protective against such susceptibility. Regular physical activity and a diet with a high consumption of fruit and cereals may help reduce depressive symptoms, but sociodemographic features are as much as important as lifestyle habits.

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data.

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.

Determinants of satisfaction with life and self-esteem in women with breast cancer.

PURPOSE: To determine satisfaction with life (LISAT) and self-esteem in women with breast cancer and the relation between sociodemographic and clinical variables with LISAT and self-esteem. METHODS: Cross-sectional study with 514 Spanish women with breast cancer. Data were collected using an online questionnaire that included the Satisfaction with Life Questionnaire (LISAT-8) and the Rosenberg self-esteem scale. Variables are age, education, occupation, marital status, surgical treatment, breast reconstruction, adjuvant treatment, time since diagnosis, the self-esteem scale, and the LISAT. A multinomial logistic regression was performed to identify possible factors associated with the LISAT and self-esteem after breast cancer. RESULTS: The average age was 46.34 (SD ± 8.28), average age at diagnosis was 42.26 (SD ± 8.56), and average time since diagnosis was 4.05 years (SD ± 5.23). Reports showed the following: good general LISAT (61.7%), economic LISAT (44.7%), and social life LISAT (75.9%) and medium sexual LISAT (41.2%). Of the respondents, 39% had lower self-esteem (p < 0.001). Those who were working (p = 0.002) and those with breast reconstruction (p < 0.037) had a good LISAT. Women with mastectomies had a worse LISAT (p < 0.001). Self-esteem was associated with the general LISAT (Pearson = 0.536, p < 0.001), social LISAT (Pearson = 0.502, p < 0.001), and sexual LISAT (Pearson = 0.329, p < 0.001). CONCLUSIONS: Women with breast cancer had a good LISAT overall; the sexual aspect was evaluated as the lowest in terms of life satisfaction. Marital status, occupation, surgical treatment and self-esteem are associated with the LISAT. Health professionals should know the variables that influence life satisfaction of women with breast cancer to plan and conduct appropriate nursing care.

Chronotype, nursing activity, and gender: A systematic review.

AIM: To synthesize evidence about the effect of individual circadian preference (chronotype) and gender in the development of sleep and mood problems in nursing professionals. BACKGROUND: Shift workers are more prone to having unhealthy habits and unfavourable clinical conditions than nonshift workers. These associations are mediated by chronotype and gender differences have also been detected. DESIGN: A quantitative systematic review. DATA SOURCES: Electronic searches were performed in MEDLINE, Scopus, ScienceDirect, and Web of Science from 1 July 2012 - 1 July 2017. REVIEW METHODS: A systematic review was conducted using the Cochrane Collaboration guidelines and two quality assessment tools: the National Heart, Lung and Blood Institute and GRADE. Inclusion criteria were quantitative studies where the sample consists entirely of nurses, analysing circadian rhythms or individual chronotype or gender and sleep/mood disturbances in nursing activity. The review was reported using the PRISMA statement. RESULTS: A total of 23 studies were included in the review (five cohort studies and 18 cross-sectional studies). Data on gender-specific attention were scarce (two studies) and showed a higher incidence of sleep problems. Female nurses with eveningness-oriented personality seem to be more prone to having sleep disorders, insomnia, fatigue, and anxiety than male and morningness ones. CONCLUSIONS: Evidence seems to show that female nurses with an evening-oriented preference suffer more problems of insomnia, sleepiness, fatigue, and anxiety. The impact of our results may affect nurses, patient safety and the quality of clinical practice.

Relationships among general health, job satisfaction, work engagement and job features in nurses working in a public hospital: A cross-sectional study.

AIM AND OBJECTIVE: To describe relations among health, job satisfaction, work engagement and job features in Spanish nurses working in a public hospital. BACKGROUND: It has been established that nursing staff health affects the quality of their work and is associated with job satisfaction, work engagement and different job features. Understanding the relationships among these variables could provide useful information to improve staff performance and prevent work-related illnesses. DESIGN: A descriptive, cross-sectional, correlational and comparative study was performed between January-April 2016. This research adheres to the Strengthening the Reporting of Observational Studies in Epidemiology guideline. METHODS: A total of 926 nurses were requested to complete an online questionnaire. Nurses on sick leave or in period of unpaid leave during data collection were excluded. The final study population reached 392 nurses. The online survey was fully completed by 373 nurses. General health, job satisfaction and work engagement were measured. Tools used were as follows: sociodemographic questions, the General Health Questionnaire, the Overall Job Satisfaction Scale and the Utrecht Work Engagement Scale. RESULTS: Significant correlations among general health, job satisfaction and work engagement were found. Specifically, general health levels were negatively correlated with job satisfaction and work engagement subscales. Job features with influence on these constructs were the type of shift, type of contract, type of service, salary, type of continuous formation and having a specialty/profile. CONCLUSIONS: Our results indicate that job-related features affect job satisfaction, general health and work engagement. The organisation should make interventions over these features to increase job satisfaction and work engagement levels, since they are relevant for nursing staff health and patient security. RELEVANCE TO CLINICAL PRACTICE: The analysis of the relationships among general health, job satisfaction, work engagement and job features in nurses could offer a basis to design preventive programmes to improve staff performance and prevent work-related illnesses.