Disease-related Determinants Research Articles

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Identifying definite patterns of unmet needs in patients with multiple sclerosis using unsupervised machine learning

IntroductionPeople with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants.MethodsWe conducted a cross-sectional multicentre study. Data were collected through an anonymous, self-administered online form. To cluster PwMS according to their main unmet needs, we performed agglomerative hierarchical clustering algorithm. Principal component analysis (PCA) was applied to visualize cluster distribution. Pairwise comparisons were used to evaluate demographics and clinical distribution among clusters.ResultsOut of 1764 mailed questionnaires, we received 690 responses. Access to primary care was the main contributor to the overall unmet need burden. Four patterns were identified: cluster C1, ‘information-seekers with few unmet needs’; cluster C2, ‘high unmet needs’; cluster C3, ‘socially and assistance-dependent’; cluster C4, ‘self-sufficient with few unmet needs’. PCA identified two main components in determining the patterns: the ‘public sphere’ (access to information and care) and the ‘private sphere’ (need for assistance and social life). Older age, lower education, longer disease duration and higher disability characterized clusters with more unmet needs in the private sphere. However, demographic and clinical factors failed in explaining the four identified patterns.ConclusionOur study identified four unmet need patterns among PwMS, emphasizing the importance of personalized care. While clinical and demographic factors provide some insight, additional variables warrant further investigation to fully understand unmet needs in PwMS.

Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis. Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population. In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6. Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

Fatigue in patients with rheumatic and musculoskeletal diseases: a scoping review on definitions, measurement instruments, determinants, consequences and interventions

ObjectivesTo scope published reviews addressing fatigue in rheumatoid arthritis (RA), spondyloarthritis, osteoarthritis and fibromyalgia in areas relevant for clinical practice: (1) definition, (2) measurement instruments and diagnosis, (3) determinants, (4)...

Factors associated with baseline quality of life in patients with oral cavity and oropharyngeal cancer.

e18079 Background: Baseline quality of life (QOL) predicts for survival in head and neck cancer patients. The purpose of this study was to identify factors contributing to baseline QOL in patients with newly diagnosed oral cavity or oropharyngeal cancer (OCOPC) in order to identify potential targets for intervention. Methods: 115 patients with OCOPC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and Brief Health Literacy Screen (BHLS). Pearson correlation and ANOVA statistics were used to analyze the data. Results: The median global health-related QOL score was 66.7 (IQR: 50, 83.4); 35.7% of participants reported anxiety and 18.3% reported depressive symptoms (HADS ≥8); 30.8% of patients had BHLS values of ≤ 9. Factors associated with significant decrease in global health-related QOL score: household income of < $20,000/year (p = .010); low health literacy (p = .021); having symptoms of anxiety (p < .001); having depressive symptoms (p < .001); and non-HPV associated cancer (p < .001). Increased tumor stage, older age, single/widowed marital status, and unemployment were associated with the lower scores on the physical QOL subscale (p < .05). Increased tumor stage was associated with lower scores on role and social QOL subscales (p < .05), and younger age was associated with lower scores on emotional QOL subscale (p < .05). Conclusions: Baseline QOL is associated with socioeconomic and disease-related determinants. Clinical trial information: NCT02412241.

Impact of patient-reported nasal symptoms on quality of life after endoscopic pituitary surgery: a prospective cohort study.

Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative HRQoL is therefore important. This study assessed the impact of nasal symptoms on postoperative HRQoL. This perioperative cohort study included 103 adult patients undergoing endoscopic pituitary adenoma resection (August 2016-December 2018), with measurements preoperatively, and 5days, 6weeks and 6months after surgery. Nasal symptoms were measured with the Anterior Skull base nasal inventory-12, and HRQoL with the Short Form-36 (SF-36) physical (PCS) and mental component scores (MCS). Linear regression analysis was used to assess (1) determinants of postoperative nasal morbidity, (2) associations between number of symptoms or (3) individual symptoms and HRQoL, and (4) the percentage of variance of HRQoL explained by nasal symptoms. The number of nasal symptoms transiently increased after surgery. No significant treatment- or disease-related determinants of nasal morbidity were identified. The number of nasal symptoms was significantly associated with a lower PCS (β = -1.0; 95%CI -1.5, -0.4), but not with MCS at 6weeks. Similar results were observed at 6months. Headaches (42.2%), problems with smell (42.0%), and taste (36.0%) were the most prevalent symptoms, while sense of smell and taste, and nasal discharge showed the strongest associations with HRQoL. Postoperative nasal symptoms, in particular problems with smell and taste, significantly affect pituitary patients' physical HRQoL. Monitoring of these symptoms may aid in determining which patients may benefit from intensified follow-up and treatment, aiming to optimize HRQoL.

Predictors of hypertension detection in English general practices: a cross sectional study.

Worldwide, high systolic blood pressure is the leading risk factor for deaths and disability-adjusted life-years but has been historically under-detected. This study aimed to quantify differences between estimated and practice-detected prevalences of hypertension across English general practices, and to determine how variations in detected prevalence could be explained by population-level and service-level factors. Descriptive statistics, pair wise correlations between the independent variables and a multivariable regression analysis were undertaken. In the regression model, the outcome was detected hypertension prevalence, adjusted for estimated prevalence, person-related and disease-related determinants of illness and characteristics of general practices. Detected prevalence was substantially lower than estimated prevalence (mean difference 16.23%; standard deviation 2.88%). Higher detected prevalence was associated with increased deprivation, increased non-white ethnicity and urban location. Lower detected prevalence was associated with larger list sizes, more general practitioners and being located in the South outside London. The final multivariable model's adjusted R2 value was 0.75. Substantial under-detection of hypertension is widespread across England. Independent of estimated prevalence, factors associated with greater morbidity and population density predicted higher detected prevalence. Identifying patients with undetected hypertension and coordinating care for these patients will require further resources and logistical support in community settings.

Brought in dead cases to a tertiary referral paediatric emergency department in India: a prospective qualitative study

ObjectivesBrought in dead (BID) presentation is profoundly related to prehospital variables including disease-related determinants and social and system-related factors. Identifying these factors would help us recognise various gaps in health...

Sociodemographic, personal, and disease-related determinants of referral to patient-reported outcome-based follow-up of remote outpatients: a prospective cohort study

PurposeWe examined the association between sociodemographic, personal, and disease-related determinants and referral to a new model of health care that uses patient-reported outcomes (PRO) measures for remote outpatient follow-up (PRO-based follow-up).MethodsWe conducted a prospective cohort study among outpatients with epilepsy at the Department of Neurology at Aarhus University Hospital, Denmark. Included were all persons aged ≥ 15 years visiting the department for the first time during the period from May 2016 to May 2018. Patients received a questionnaire containing questions about health literacy, self-efficacy, patient activation, well-being, and general health. We also collected data regarding sociodemographic status, labour market affiliation, and co-morbidity from nationwide registers. Associations were analysed as time-to-event using the pseudo-value approach. Missing data were handled using multiple imputations.ResultsA total of 802 eligible patients were included in the register-based analyses and 411 patients (51%) responded to the questionnaire. The results based on data from registers indicated that patients were less likely to be referred to PRO-based follow-up if they lived alone, had low education or household income, received temporary or permanent social benefits, or if they had a psychiatric diagnosis. The results based on data from the questionnaire indicated that patients were less likely to be referred to PRO-based follow-up if they reported low levels of health literacy, self-efficacy, patient activation, well-being, or general health.ConclusionBoth self-reported and register-based analyses indicated that socioeconomically advantaged patients were referred more often to PRO-based follow-up than socioeconomically disadvantaged patients.

Sociodemographic and disease-related determinants of return to work among women with breast cancer: a German longitudinal cohort study

BackgroundReturn to work (RTW) is a key parameter of outcome quality that ensures social participation. Therefore, this study analyses the sociodemographic and disease-related determinants of RTW among newly diagnosed breast cancer patients.MethodsIn a prospective, multicentre cohort study, breast cancer patients were surveyed three times: directly after surgery, after 10 weeks, and after 40 weeks. Logistic regression analysis was applied to estimate the association of RTW at 40 weeks following discharge with sociodemographic and disease-related characteristics (n = 577).ResultsThe sociodemographic variables “entrance certificate at a university of applied science” compared to “university entrance certificate” (OR = 3.1, 95%-CI = 1.2–8.1), age group “55–59 years” compared to “18–44 years” (OR = 3.2, 95%-CI = 1.2–8.4) and “having children” (OR = 2.8, 95%-CI = 1.2–6.2) as well as the disease-related variables “rehabilitation” (OR = 0.5, 95%-CI = 0.3–0.9), self-rated health “good” and “excellent” compared to “bad” (OR = 2.7, 95%-CI = 1.4–5.5; OR = 11.6, 95%-CI = 4.2–31.8) and the UICC-classification “stage II” and “stage III/IV” in comparison to “stage 0/I” (OR = 0.5, 95%-CI = 0.3–0.8; OR = 0.2, 95%-CI = 0.1–0.5) significantly affect RTW among breast cancer patients (Nagelkerke’s Pseudo-R2 = 0.275).ConclusionsThe findings show that significant differences in RTW exist between patient groups and suggest that RTW issues must be addressed more effectively before, during and after treatment. For future research on RTW in Germany, longitudinal studies with a follow-up of several years are necessary. Information and support deficits should be tackled by social services or breast care nurses.Trial registrationDatabase Health Services Research, VfD_PIAT_12_001630, registered 01.03.2012

Quality of Life of Pakistani Children with β-Thalassemia Major

Compromised quality of life (QoL) has been reported in individuals suffering from β-thalassemia major (β-TM) in Pakistan. However, insufficient data of its associated psychosocial, physical and other disease-related determinants is available. In an observational analytical study, 200 subjects aged between 5-25 years, were examined using a transfusion-dependent QoL (TranQoL) questionnaire. Clinical records and other related data were also gathered from transfusion center databases. The TranQoL mean score was 48.33 ± 5.6, ranging from 53.86 ± 13.6 for family functioning and support domain to 39.70 ± 18.4 for school and career functioning domain. Age, income, education, pre transfusion hemoglobin (Hb), serum ferritin level, pain, death due to β-thal, monetary issues and pain were significantly associated with TranQoL scores. It was not only the clinical conditions but life alterations, social relationship and psychological events also loomed in improvement of treatment outcomes. Therefore, a tetra-cone of patient, school representatives, family and physicians are needed for better patient prospective.

Determinants of delay in timely treatment seeking for diarrheal diseases among mothers with under-five children in central Ethiopia: A case control study.

BackgroundDelays in seeking timely appropriate care contributes to a large number of deaths from diarrhea in children. This study aimed to identify determinants of delays in seeking timely treatment by mothers/caregivers of under-five children with diarrheal diseases.MethodsWe used an unmatched case-control study from February—March 2017 among 316 children: 158 cases and 158 controls. Cases were mothers/caregivers with under-five children who had signs/symptoms of diarrhea and sought treatment after 24 hours onset of symptom. Controls sought treatment within 24 hours. Field workers collected data using a pre-tested standardized questionnaire. Multivariate logistic regression was conducted to identify determinants of delay in timely diarrhea treatment seeking. Statistical significance was declared by using a p-value<0.05 and 95% of confidence interval (CI) for an adjusted-odds ratio (AOR).ResultsThe determinants of delay in timely treatment seeking of mothers/caregivers of under-five children with diarrheal diseases were children <24months (AOR = 1.9,95%CI:1.1–3.4); fail to attend school (AOR = 2.4, 95%CI:1.2–4.6); being female children (AOR = 1.7,95%CI:1.05–2.9); preferring government health facility for the treatment of children with diarrheal diseases (AOR = 2.9, 95%CI, 1.3–6.7); lack of past history taking children to health facility and lack of counseling (AOR = 4.8, 95%CI:2.0–12.1); being in the15-25 years age (AOR = 1.7, 95%CI:1.1–3.0) and taking children to a health facility as a first response to diarrhea (AOR = 0.1, 95%CI:0.01–0.8).ConclusionsAge of the child, maternal age, and disease related determinants were determinants for seeking timely treatment to diarrheal diseases. Providing skilled based health education and counseling to mothers/caregivers on seeking timely treatment and taking children with diarrheal diseases to a health facility as a first response to diarrhea is a paramount intervention to reduce morbidity and mortality of children.

Disease-related determinants are associated with mortality in dementia due to Alzheimer\u2019s disease

BackgroundSurvival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer’s disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD.MethodsWe included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort. Information on mortality was obtained from the Dutch Municipal Register. We used age- and sex-adjusted Cox proportional hazards analysis to study associations of baseline demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI) (medial temporal lobe, global cortical and parietal atrophy, and measures of small vessel disease), and cerebrospinal fluid (CSF) (β-amyloid 1–42, total tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome). In addition, we built a multivariate model using forward selection.ResultsAfter an average of 4.9 ± 2.0 years, 213 (35%) patients had died. Age- and sex-adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12–1.48]), male sex (HR 1.60 [95% CI 1.22–2.11]), worse scores on cognitive functioning (HR 1.14 [95% CI 1.01-1.30] to 1.31 [95% CI 1.13–1.52]), and more global and hippocampal atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were associated with increased risk of mortality. There were no associations with comorbidity, level of activities of daily living, apolipoprotein E (APOE) ε4 status, or duration of disease. Using forward selection, the multivariate model included a panel of age, sex, cognitive tests, atrophy of the medial temporal lobe, and CSF p-tau.ConclusionsIn this relatively young sample of patients with AD, disease-related determinants were associated with an increased risk of mortality, whereas neither comorbidity nor APOE genotype had any prognostic value.

The determinants of reduced dietary intake in hospitalised colorectal cancer patients

PurposePatients with colorectal cancer (CRC) often experience malnutrition and weight loss, largely resulting from reduced dietary intake. The aim of this study was to identify determinants of reduced dietary intake in order to facilitate early recognition of malnutrition and optimise nutritional treatment.MethodsData from nutritionDay, an international 1-day survey investigating patient, disease and food profiles, were used. To identify determinants of dietary intake, defined as normal vs. reduced in the last week, univariate and multivariate logistic regressions were performed.ResultsOf 1131 hospitalised CRC patients, 54% reported reduced dietary intake. Patient- and disease-related characteristics significantly associated with reduced dietary intake were female gender (odds ratio (OR) 1.38), cancer stage III (OR 1.52) or IV (OR 1.70) vs. I, performance status 2 (OR 1.56), 3 (OR 2.37) or 4 (OR 4.15) vs. 0, duration since hospital admission of ≥ 4 days (OR 4–7 days, 1.91; 8–21 days, 1.97; > 21 days, 1.92) vs. < 4 days, and unintentional weight loss (OR 2.56). Additionally, higher symptom scores of pain, weakness, depression, tiredness and lack of appetite were associated with reduced intake.ConclusionsPatient- and disease-related determinants for reduced dietary intake were being female, higher cancer stage, worse performance status, duration since hospital admission ≥ 4 days and unintentional weight loss. Furthermore, multiple symptoms were associated with a reduced dietary intake. Future trials should assess whether early recognition of patients at risk of malnutrition and the combination of treating symptoms and dietary advice result in improved intake and treatment-related outcomes.

Determinants of Quality of Life and Return to Work Following Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) in adults is a consequence of lung damage caused by either pulmonary or extrapulmonary disease. Survivors often suffer from an impaired health-related quality of life (HRQoL), mental and physical impairments, and persistent inability to work. In this systematic review of the literature, we consider the determinants of HRQoL and return to work (RtW). 24 observational studies showing a statistical association between one or more determinants and HRQoL or RtW were included. Because of the heterogeneity of these studies, no statistical aggregation of the individual effect estimates was carried out; instead, the results are summarized descriptively. Psychopathological manifestations, in particular, are associated with impaired quality of life. In contrast, many care- and disease-related determinants had only small, non-significant effects on HRQoL and RtW. The onesecond capacity was found in all studies to be positively associated with the HRQoL. ARDS induced by sepsis seems to be a risk factor for a lower HRQoL in comparison to ARDS of other causes. A synthesis of the evidence is impeded both by the high level of heterogeneity of studies and by the high risk of selection bias in all studies. The identification of determinants of impaired quality of life after ARDS is essential for the assessment of clinically relevant interventions. In multiple studies, major significant effects were only observed when determinants the content of which was closely related to the scales of the HRQoL instruments were measured at the same time as the HRQoL.

Childhood central nervous system tumour mortality and survival in Southern and Eastern Europe (1983–2014): Gaps persist across 14 cancer registries

AimChildhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region. MethodsAverage age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan–Meier curves were derived for the maximum and the more recent (10 and 5year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants. ResultsVariations in mortality (8–16 per million) and survival (5-year: 35–69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (−2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1–1.4). ConclusionCross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe.

Disease-related determinants of quality of life 10 years after clinically isolated syndrome.

The main clinical determinants of quality of life (QOL) 5 years after clinically isolated syndrome (CIS) are Expanded Disability Status Scale (EDSS) score and conversion to clinically definite multiple sclerosis (CDMS). The aim of this study was to determine the demographic, clinical, and magnetic resonance imaging (MRI) factors associated with QOL 10 years after CIS. Controlled High Risk Avonex® Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS) 10-year patients were assessed for CDMS, EDSS score, MRI T2 activity, brain parenchymal fraction, and patient-reported QOL. Associations were evaluated using analysis of variance models. A second clinical event consistent with CDMS and higher EDSS scores at years 5 and 10 were associated with lower 36-item Short Form Health Status Survey (SF-36) Physical Component Summary scores at year 10 (P < .01). Patients with earlier onset of CDMS had worse patient-reported Physical Component Summary, SF-36 Mental Component Summary, fatigue, and pain scores at year 10 than patients with later or no onset of CDMS. Neither initial randomization group nor any MRI metrics assessed at baseline or during follow-up were associated with QOL at 10 years. These results support the development of therapies for patients with CIS that significantly reduce the risk of conversion to CDMS and the progression of physical disability to milestones as low as EDSS scores of 2.0.

How to manage thrombosis in myeloproliferative neoplasms

In this article, an updated overview of risk factors and management of vascular complications in myeloproliferative neoplasms (MPN) is presented. The rate of thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis is elevated and a risk-oriented therapeutic approach is recommended to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established thrombosis risk factors are age and previous vascular events but novel disease-related determinants such as leukocytosis and JAK2V617F mutational status and/or mutational burden are now under active investigation. The theory that elevated platelet count increases thrombosis risk in these diseases is now challenged. Recent recommendations by the European Leukemia Net suggest that MPN patients should be stratified and treated according to conventional risk factors (age and previous events) and that baseline leukocytosis and JAK2V617F mutation should be considered once more information is available and when they have been eventually validated in prospective studies.

Mental Disorder and Psychologic Distress in Patients With Ulcerative Colitis After Ileal Pouch-Anal Anastomosis

The aim of this study was to determine if ileal pouch-anal anastomosis in patients with ulcerative colitis is a psychologic burden for patients, the frequency of mental disorders, the amount of psychologic distress, and their possible disease-related determinants. These factors were studied in patients with ulcerative colitis after ileal pouch anal anastomosis and were compared with ulcerative colitis patients without ileal pouch-anal anastomosis and the general German population. A total of 37 patients with ulcerative colitis after ileal pouch-anal anastomosis (age 46.8 +/- 11.8 years; 35 percent female) and 62 patients with ulcerative colitis without ileal pouch-anal anastomosis (age 44.4 +/- 13.9 years; 37 percent female) completed the following questionnaires: medical and sociodemographic questionnaire of the German Competence Network "Inflammatory Bowel Diseases" and the German version of the Hospital Anxiety and Depression Scale. Disease activity was measured in patients with ileal pouch-anal anastomosis by the Pouch Disease Activity Index and in patients without ileal pouch-anal anastomosis by the German Inflammatory Bowel Disease Activity Index. Psychologic distress was assessed by the subscale scores of the Hospital Anxiety and Depression Scale. A probable mental disorder was identified if a patient scored 11 or higher in at least one subscale of the Hospital Anxiety and Depression Scale. The frequency of a probable psychiatric disorder in patients with ileal pouch-anal anastomosis (16 percent) and without ileal pouch-anal anastomosis (23 percent) did not differ from that in the general German population (17 percent). Ulcerative colitis patients with or without ileal pouch-anal anastomosis did not differ in the amount of psychologic distress. Ileal pouch-anal anastomosis patients had higher levels of anxiety than the general population (P < 0.01). Regression models of disease-related factors predicting mental disorder and psychologic distress showed no significant results. Ileal pouch-anal anastomosis neither increases nor decreases the frequency of mental disorders or the amount of psychologic distress in ulcerative colitis patients.

Animal models of human disease in drug safety assessment.

Animal models of human disease have been widely used in drug discovery, but they are rarely utilized in toxicological research and screening (except for transgenic models in carcinogenicity testing). Although genetic and/or acquired pathophysiological alterations associated with a particular disease may greatly exacerbate toxic responses to drugs in certain patient subsets, these pre-existing pathological conditions are usually not considered in preclinical safety assessment. Examples of disease-related determinants of susceptibility include disruption of the cytokine network in pro-inflammatory conditions, mitochondrial alterations and oxidative stress in certain neurodegenerative diseases, altered antioxidant defense in certain viral infections, and altered gene expression and mitochondrial dysfunction in type 2 diabetes. Hence, if cellular stress caused by drugs or metabolites and the disease-related effects are superimposed, then an individual can become sensitized to potential drug toxicity. Animal models of modest inflammation indeed can potentiate the toxicity of certain drugs. Similarly, rodent models of type 2 diabetes predispose the animals to hepatotoxic effects of thiazolidinediones antidiabetics. In conclusion, it is suggested that tailor-made and simplified models be adopted and increasingly used, in spite of clear limitations, as optimal substrates for satellite toxicity studies to facilitate candidate selection, help predict rare and unexpected toxicity, and identify new biomarkers.