ABSTRACT
BACKGROUND: Mothers of people with intellectual disabilities (IDs) face exceptional challenges and may be more prone to experiencing mental ill-health compared with mothers of typically developing people. These mental ill-health problems may differ at different stages of the caregiving trajectory. However, there is no evidence synthesis on this topic. We aimed to systematically review evidence in this area and identify gaps in the existing literature. METHOD: Prospero registration: CRD42018088197. Medline, Embase, CINAHL and PsycINFO databases were searched. No time limits were applied. Studies were limited to English language. Inclusion criteria were studies of mothers of people with IDs that also included a comparison group of mothers of typically developing/developed children. Data were extracted from selected studies using a structured database. Study selection and quality appraisal were double rated. Where possible, meta-analyses were performed. RESULTS: Of the retrieved articles, 32/3089 were included, of which 10 reported on anxiety, 21 on depression and 23 on other indicators of mental ill-health. Overall, previous studies reported that mothers of people with IDs experienced poorer mental health as compared with mothers of typically developing people. Meta-analyses revealed significant findings for anxiety, depression, parenting stress, emotional burden and common mental disorders, but not for somatic symptoms. However, there was a considerable heterogeneity; hence, interpretation of results should be cautious. Identified gaps included scarce research on mental ill-health of mothers of adults with IDs at different stages of the caregiving trajectory. CONCLUSIONS: There is evidence of poorer mental ill-health in mothers of people with IDs compared with mothers of typically developing people, but lack of focus on different stages of the caregiving trajectory, methodological inconsistencies between studies and lack of robust studies pose limitations. This highlights the need both for improved support for mothers of people with IDs and for further methodologically robust research.
Subject(s)
Intellectual Disability , Mothers , Anxiety Disorders , Female , Humans , Intellectual Disability/epidemiology , Mental Health , ParentingABSTRACT
BACKGROUND: Several drugs have anticholinergic side effects that are associated with adverse health outcomes. Anticholinergic burden studies in adults with intellectual disabilities (ID) have focused exclusively on older adults. This study investigates anticholinergic burden and its associations in adults with ID of all ages (17-94 years). METHODS: Adults with ID (n = 4 305), each with three general population age-sex-neighbourhood-matched controls (n = 12 915), were linked to their prescribed medications with anticholinergic effects between 2009 and 2017. Analyses were undertaken using logistic regression models. RESULTS: Adults with ID were more likely to be prescribed any anticholinergic medicines, odds ratio (OR) = 1.49 (1.38-1.59), especially 'very strong' risk medicines, OR = 2.59 (2.39-2.81); 48.5% had very high total anticholinergic burden (3+) compared with 35.4% of the general population, OR = 1.77 (1.64-1.90). This group difference was greater for males, OR = 2.02 (1.84-2.22), than females, OR = 1.48 (1.33-1.65). Adults with ID had significantly higher odds of having very high total anticholinergic burden up to 75 years old, with the greatest group effect occurring in younger ages, 17-24-year-olds, OR = 3.05 (2.39-3.89), and the extent of the difference decreased as age increased. The main effect of neighbourhood deprivation showed greater group differences with increasing affluence of neighbourhood. Results examining only the ID group showed that very high total anticholinergic burden was greatest for females, OR = 1.21 (1.07-1.37), and those over age 55, and extent of neighbourhood deprivation was not significant. CONCLUSIONS: Adults with ID are at higher risk of anticholinergic burden than the general population, especially young adults. Overall anticholinergic burden increased with age, but burden was high across all ages in the ID group. Very high total anticholinergic burden is prevalent across all types of neighbourhoods for the adults with ID, in contrast to the steeper gradient seen in the general population. Adults with ID have increased likelihood of unintended adverse effects, regardless of potential confounds, so clinicians undertaking medication reviews need to consider anticholinergic side effects and cumulative burden across concomitant medications, including in young adults with ID, not just older adults, and particularly women.
Subject(s)
Cholinergic Antagonists , Intellectual Disability , Adolescent , Adult , Aged , Aged, 80 and over , Cholinergic Antagonists/adverse effects , Cross-Sectional Studies , Female , Humans , Intellectual Disability/epidemiology , Male , Medication Review , Middle Aged , Retrospective Studies , Scotland/epidemiology , Young AdultABSTRACT
BACKGROUND: Oral health may be poorer in adults with intellectual disabilities (IDs) who rely on carer support and medications with increased dental risks. METHODS: Record linkage study of dental outcomes, and associations with anticholinergic (e.g. antipsychotics) and sugar-containing liquid medication, in adults with IDs compared with age-sex-neighbourhood deprivation-matched general population controls. RESULTS: A total of 2933/4305 (68.1%) with IDs and 7761/12 915 (60.1%) without IDs attended dental care: odds ratio (OR) = 1.42 [1.32, 1.53]; 1359 (31.6%) with IDs versus 5233 (40.5%) without IDs had restorations: OR = 0.68 [0.63, 0.73]; and 567 (13.2%) with IDs versus 2048 (15.9%) without IDs had dental extractions: OR = 0.80 [0.73, 0.89]. Group differences for attendance were greatest in younger ages, and restoration/extractions differences were greatest in older ages. Adults with IDs were more likely prescribed with anticholinergics (2493 (57.9%) vs. 6235 (48.3%): OR = 1.49 [1.39, 1.59]) and sugar-containing liquids (1641 (38.1%) vs. 2315 (17.9%): OR = 2.89 [2.67, 3.12]). CONCLUSION: Carers support dental appointments, but dentists may be less likely to restore teeth, possibly extracting multiple teeth at individual appointments instead.
Subject(s)
Dental Care/methods , Dental Care/statistics & numerical data , Dental Restoration Repair/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Intellectual Disability/epidemiology , Tooth Extraction/statistics & numerical data , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Scotland/epidemiology , Young AdultABSTRACT
BACKGROUND: There have been several past reports that adults with intellectual disabilities experience poor oral health (tooth loss, periodontal health and untreated dental caries). Loss of a functional dentition has serious consequences, including problems with chewing, swallowing, nutrition, speech, temporomandibular joint osteoarthritis and pain and systemic health conditions. Poor oral health is largely preventable through proactive oral care support. In recent years, social care provision for adults has changed, with deinstitutionalisation and home-based personalised care now being the typical provision in high income countries. Hence, oral health inequalities might be reducing. However, there is limited recent evidence-synthesis on the topic. We aimed to address this. METHOD: PROSPERO registration number: CRD42018089880. We conducted a preferred reporting items for systematic reviews and meta-analyses systematic review of publications since 2008. Four databases were searched with a clear search strategy, strict inclusion criteria for selection of papers, double scoring (two raters), systematic data extraction and quality appraisal of included papers. RESULTS: A total of 33/3958 retrieved articles were included, of which 14 were drawn from dental service users and 10 from Special Olympic athletes, therefore not necessarily being representative of the wider population with intellectual disabilities. Despite this limitation, adults with intellectual disabilities were still shown to experience poor oral health. High levels of poor oral hygiene and gingivitis were found, with many also affected by periodontitis and untreated dental decay. There is clear unmet need relating to both periodontal (gum) and tooth health, leading to tooth loss. CONCLUSIONS: Despite reports in the past of poor oral health amongst adults with intellectual disabilities, and despite it being preventable, there remains a high burden of poor oral health. This highlights the need to raise awareness, and for polices on effective daily oral care, and appropriate service provision. The importance of oral health and its possible negative sequelae needs to be elevated amongst carers and professionals.
Subject(s)
Intellectual Disability/complications , Mouth Diseases/complications , Oral Health/statistics & numerical data , Tooth Diseases/complications , Adult , HumansABSTRACT
BACKGROUND: Poor oral health is largely preventable. Prevention includes toothbrushing and regular dental checks. Oral health has important consequences for general nutrition, chewing, communication, wider systemic disease, self-confidence and participation in society. This study investigated the prevalence of edentulousness (no natural teeth) in adults with intellectual disabilities (IDs) compared with the general population and associated factors. METHODS: An adult cohort with IDs residing in Greater Glasgow and Clyde, Scotland, underwent detailed health assessments between 2002 and 2004. Between 2004 and 2006, a subsample had an oral check. Data on edentulousness in the cohort were compared with adult participants from Greater Glasgow and Clyde in the 2008 Scottish Health Survey. Within the IDs cohort, binary logistic regression analyses investigated potential relationships between edentulousness and demographic and clinical factors. RESULTS: Five hundred sixty adults with IDs were examined [53.2% (298) male, mean age = 46.3 years, range 18-81 years] and compared with 2547 general population: edentulousness was 9% vs. 1% aged 25-34 years; 22% vs. 2% aged 35-44 years; 39% vs. 7% aged 45-54 years; 41% vs. 18% aged 55-64 years; and 76% vs. 34% aged 65-74 years. In both groups, edentulousness increased with age. After stratification for age, rates of edentulousness were consistently higher in the ID cohort. Odds ratios within age strata were not homogenous (Mantel-Haenszel test, P < 0.0001). Edentulousness was more likely in those with more severe IDs (adjusted odds ratio (AOR) = 2.36; 95% confidence interval (CI) [1.23 to 4.51]); those taking antipsychotics (AOR = 2.09; 95% CI [1.25 to 3.51]) and those living in the most deprived neighbourhoods (AOR = 2.69; 95% CI [1.11 to 6.50]). There was insufficient evidence for associations with sex, type of accommodation/support, antiepileptics, problem behaviours or autism. CONCLUSIONS: Adults with IDs have a high prevalence of edentulousness and need supported daily oral care to reduce the need for extractions. Despite previous reports on poor oral care and the move towards person-centred care, carers and care-giving organisations need greater support to implement daily oral care. Prescribers need awareness of the potentially contributory role of antipsychotics, which may relate to xerostomia.
Subject(s)
Intellectual Disability/epidemiology , Mouth, Edentulous/epidemiology , Oral Health/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Mouth, Edentulous/prevention & control , Prevalence , Risk Factors , Scotland/epidemiology , Young AdultABSTRACT
BACKGROUND: People with intellectual disabilities face a much greater burden and earlier onset of physical and mental ill-health than the general adult population. Physical-mental comorbidity has been shown to result in poorer outcomes in the general population, but little is known about this relationship in adults with intellectual disabilities. AIMS: To identify whether physical ill-health is associated with mental ill-health in adults with intellectual disabilities and whether the extent of physical multi-morbidity can predict the likelihood of mental ill-health. To identify any associations between types of physical ill-health and mental ill-health. METHOD: A total of 1023 adults with intellectual disabilities underwent comprehensive health assessments. Binary logistic regressions were undertaken to establish any association between the independent variables: total number of physical health conditions, physical conditions by International Classification of Disease-10 chapter and specific physical health conditions; and the dependent variables: problem behaviours, mental disorders of any type. All regressions were adjusted for age, gender, level of intellectual disabilities, living arrangements, neighbourhood deprivation and Down syndrome. RESULTS: The extent of physical multi-morbidity was not associated with mental ill-health in adults with intellectual disabilities as only 0.8% of the sample had no physical conditions. Endocrine disease increased the risk of problem behaviours [odds ratio (OR): 1.22, 95% confidence interval (CI): 1.02-1.47], respiratory disease reduced the risk of problem behaviours (OR: 0.73, 95% CI: 0.54-0.99) and mental ill-health of any type (OR: 0.73, 95% CI: 0.58-0.92), and musculoskeletal disease reduced the risk of mental ill-health of any type (OR: 0.84, 95% CI: 0.73-0.98). Ischaemic heart disease increased the risk of problem behaviours approximately threefold (OR: 3.29, 95% CI: 1.02-10.60). CONCLUSIONS: The extent of physical multi-morbidity in the population with intellectual disabilities is overwhelming, such that associations are not found with mental ill-health. Mental health interventions and preventative measures are essential for the entire population with intellectual disabilities and should not be focussed on subgroups based on overall health burden.
Subject(s)
Chronic Disease/epidemiology , Health Status , Intellectual Disability/epidemiology , Mental Disorders/epidemiology , Adolescent , Adult , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Scotland/epidemiology , Young AdultABSTRACT
BACKGROUND: Medically unexplained symptoms and signs are common in the general population and can respond to appropriate managements. We aimed to quantify the types and prevalence of unexplained symptoms and signs experienced by adults with ID and to determine the associated factors. METHOD: In a population-based study, 1023 adults with ID aged 16 and over had a detailed health assessment, which systematically considered symptoms and signs. Descriptive data were generated on their symptoms and signs. Backwards stepwise logistic modelling was undertaken to determine the factors independently associated with the unexplained symptoms. RESULTS: Medically unexplained symptoms and signs were present in 664 (64.9%), 3.8 times higher than in the general population, and 470 (45.9%) had multiple unexplained symptoms or signs. Some were similar to those reported in the general population, such as dyspnoea, dyspepsia, headache, nausea and dizziness. However, others are not commonly reported in the general population, including dysphagia, ataxia, polyuria, oedema and skin rash. Having unexplained symptoms and signs was independently associated with older age, female gender, not having Down syndrome, extent of ID and more GP visits in the last 12 months. It was not associated with living in deprived areas, type of living/support arrangements, number of hospital visit in the last 12 months, smoking, autism, problem behaviours or mental disorders. CONCLUSIONS: People with ID have substantial additional unexplained symptoms and signs, some of which are painful or disabling. These findings should inform the content of health checks undertaken for adults with intellectual disabilities, which should not just focus on management of their long-term conditions and health promotion.
Subject(s)
Intellectual Disability/epidemiology , Medically Unexplained Symptoms , Somatoform Disorders/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Scotland/epidemiology , Young AdultABSTRACT
Modelling: what do we know, what do we want to know and why? The practical application of models to real projects is often circular because these questions weren't asked prior to making the decision to model the plant under study. Modelling wastewater treatment plants can provide insight into the inner workings of the process that might not be attainable any other way, but is that added process knowledge always needed or necessary and what criteria does one use to determine the level of effort required? These complex modelling decisions require education, communication, and improved understanding amongst both modellers and clients. This submission explores the use of models by consultants for consulting purposes and the balancing acts (time versus knowledge and cost versus benefit) that the consulting engineer must manage when embarking on any modelling project.
Subject(s)
Models, Educational , Sanitary Engineering/education , Sanitary Engineering/methods , Humans , Risk Factors , Sanitary Engineering/economics , Time FactorsABSTRACT
In activated sludge wastewater treatment research, most of the attention has been devoted to the biodegradation process. However, in terms of effluent quality, the final settling and clarification processes are at least as important because any particle carried over the overflow weir brings with it not only COD, but also nitrogen and phosphorus. In recent years we see indeed increased attention on this separation step, and alternatives such as membrane separation are increasingly introduced. Still, a large installed base of settlers exists, whose operation could/should be optimised. The measurement techniques presented in this contribution each focus on one of the key processes in the secondary settler: hydrodynamics, particle aggregation and breakage, hindered settling and compression. For each technique, the measuring principle is explained and a typical data set shown.
Subject(s)
Waste Disposal, Fluid , Flocculation , Particle SizeABSTRACT
The submucosal venous network of the esophagus is part of the collateral system that develops following superior vena caval obstruction from any cause. The direction of flow in these thin-walled, valveless veins is "downhill," towards the azygous vein or to the inferior vena cava. Bleeding from upper esophageal varices is extremely rare. This case report describes a patient with massive bleeding from upper esophageal varices secondary to superior vena caval obstruction by a malignant thyroid tumor. Total thyroidectomy relieved the obstruction, with cessation of hemorrhage and subsequent disappearance of the varices.
Subject(s)
Esophageal and Gastric Varices/etiology , Thyroid Neoplasms/complications , Vena Cava, Superior , Aged , Esophageal and Gastric Varices/diagnostic imaging , Female , Gastrointestinal Hemorrhage/etiology , Humans , Radiography , Thyroid Neoplasms/surgery , Thyroidectomy , Vascular Diseases/complications , Vascular Diseases/etiologySubject(s)
Diverticulum, Esophageal/diagnostic imaging , Aged , Diagnosis, Differential , Female , Humans , RadiographyABSTRACT
At least 150 cases of mushroom poisoning occur in Canada each year, 75% in the Province of Ontario. Eighty per cent of the total are in children under the age of 9, and most do not require hospitalization. Amanita virosa poisoning is a potentially fatal medical emergency which presents as an acute gastroenteritis, progressing to hepatorenal failure. Treatment consists of elimination of undigested mushrooms, rapid rehydration, management of acute liver and renal failure, and prevention of infection during the recovery phase.
Subject(s)
Mushroom Poisoning/epidemiology , Adult , Autopsy , Canada , Humans , Liver Cirrhosis/pathology , Male , Mushroom Poisoning/pathology , Mushroom Poisoning/therapyABSTRACT
PURPOSE: Groin injuries are a major diagnostic and therapeutic challenge in sports medicine. The aim of this review is to describe the clinical and surgical findings associated with an atypical lower abdominal pain syndrome occurring in elite ice hockey players. CASE SUMMARIES: Eleven professional ice hockey players from various National Hockey League teams were referred to the Montreal General Hospital between 1989 and 1996, suffering from atypical refractory pain and paraesthesia in the lower abdomen. Despite the use of conventional investigative procedures such as physical examination, ultrasound, bone scan, computed tomography scan, and magnetic resonance imaging scan, preoperative findings were consistently negative. Operative findings revealed varying degrees of tearing of the external oblique aponeurosis and external oblique muscle associated with ilioinguinal nerve entrapment. Repair of the external oblique tear, ablation of the ilioinguinal nerve, followed by a 12-week planned course of physiotherapy allowed all to return to professional ice hockey careers. DISCUSSION: While soft tissue injuries are the most common cause of groin pain in the athlete, tears of the external oblique aponeurosis and superficial inguinal ring have rarely been cited as a consistent cause of lower abdominal pain in athletes. Inguinal nerve entrapment is also rare in patients without a history of previous lower abdominal surgery. RELEVANCE: These 11 cases emphasize the importance of including another diagnostic possibility in the differential diagnosis of chronic overuse injuries of the lower abdomen.
Subject(s)
Abdominal Pain/etiology , Groin/injuries , Hockey/injuries , Inguinal Canal/innervation , Nerve Compression Syndromes/complications , Adult , Athletic Injuries/physiopathology , Biomechanical Phenomena , Humans , Male , Nerve Compression Syndromes/physiopathologyABSTRACT
The results of treatment of 13 consecutive cases of antibiotic-associated pseudomembranous colitis with oral metronidazole are described. The diagnosis was made by typical sigmoidoscopic appearance with a confirming characteristic colonic biopsy specimen and/or stools positive for Clostridium difficile cytotoxin. All patients responded with the disappearance of diarrhea between 1 and 5 days. Two patients experienced relapse when the therapy was discontinued. Our experience with metronidazole shows that it is an effective treatment for antibiotic-associated pseudomembranous colitis. The response to metronidazole treatment compares favorably with that usually obtained with vancomycin.
Subject(s)
Anti-Bacterial Agents/adverse effects , Enterocolitis, Pseudomembranous/chemically induced , Metronidazole/therapeutic use , Adult , Aged , Enterocolitis, Pseudomembranous/drug therapy , Female , Humans , Male , Middle Aged , Vancomycin/therapeutic useABSTRACT
We report 3 patients with severe and persistent iron deficiency anemia who were found to have gastric antral vascular ectasia. Endoscopically, the patients presented with a characteristic antral appearance so distinctive as to be diagnostic: longitudinal rugal folds traversing the antrum and converging on the pylorus, each containing a visible convoluted column of vessels, the aggregate resembling the stripes on a watermelon; and, less prominently, evidence of mucosal prolapse. In 2 of these patients, with uncontrollable anemia, antrectomy and Billroth I anastomosis were performed; their hemoglobin levels have subsequently remained normal over the following 2 yr. In the third patient, who was achlorhydric, prednisone therapy substantially reduced the rate of bleeding. In all patients, endoscopic biopsy specimens showed dilatation of mucosal capillaries, with focal thrombosis and fibromuscular hyperplasia of the lamina propria; the resected specimens, additionally, show thickened mucosa with tortuous submucosal venous channels. The importance of the condition lies in its recognition.
Subject(s)
Gastric Mucosa/blood supply , Gastrointestinal Hemorrhage/pathology , Pyloric Antrum/pathology , Adult , Aged , Anemia, Hypochromic/etiology , Capillaries/pathology , Dilatation, Pathologic , Female , Gastric Mucosa/pathology , Gastrointestinal Hemorrhage/etiology , Gastroscopy , Humans , Hyperplasia , Hypertrophy , Muscle, Smooth, Vascular/pathology , Pyloric Antrum/blood supply , Thrombosis/complications , Thrombosis/pathologyABSTRACT
The finding, in a patient with celiac sprue, of a characteristic change at endoscopy (scalloping of the valvulae conniventes, event on close inspection, but forming only a mosaic pattern from a distance) led to an endoscopic survey designed to define its incidence. In a series of 28 sequential patients found to have microscopic changes characteristic of sprue on biopsy, distinctive endoscopic changes were found in 22 (in 6 of 9 with sprue in relapse, and 16 of 19 presenting with initial symptoms). The finding of the distinctive appearance provides an endoscopically recognizable pattern that can be associated with sprue. It also provides the potential for early recognition of the process in patients in whom the diagnosis might otherwise have been delayed due to a lack of substantial evolution of the usually associated symptom complex.
Subject(s)
Celiac Disease/pathology , Duodenum/pathology , Intestinal Mucosa/pathology , Biopsy , Celiac Disease/diagnosis , Duodenoscopy , HumansABSTRACT
BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception and function, embraces physical, social, and emotional performance but has not had a prominent role in clinical trials of inflammatory bowel disease (IBD). To test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific QOL index, this study assessed its validity, reliability, and responsiveness during a multicenter trial. METHODS: Three hundred five patients with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ and dimensional scores (bowel, social, systemic, and emotional) were correlated with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index. Regression line slopes of IBDQ scores were significantly different in patients who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a valid reliable assessment tool that reflects important changes in the health status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy and should be used in future clinical trials in IBD.
Subject(s)
Crohn Disease/psychology , Quality of Life , Adult , Crohn Disease/drug therapy , Cyclosporine/therapeutic use , Double-Blind Method , Female , Health Status , Humans , Male , Surveys and QuestionnairesABSTRACT
Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.
Subject(s)
Cimetidine/therapeutic use , Duodenal Ulcer/drug therapy , Smoking , Cimetidine/administration & dosage , Clinical Trials as Topic , Double-Blind Method , Female , Humans , Male , Middle Aged , Random Allocation , RecurrenceABSTRACT
BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.