Diagnosis and treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common medical disorder characterized by symptoms of abdominal pain and bowel dysfunction. It is associated with significant disability and health care costs. A practical approach to diagnosis is the symptom-based Rome criteria. Management of patients has been helped by recent findings relating to the epidemiology, pathophysiology and psychosocial contributions of the disorder. Dysregulation of intestinal motor, sensory and central nervous system function is currently believed to be the basis for IBS symptoms. Symptoms are due to both abnormal intestinal motility and enhanced visceral sensitivity. Psychosocial factors are not a cause but can affect the illness experience and clinical outcome. Finally, treatment involves an effective physician-patient relationship and an integrated pharmacologic and behavioral approach that is determined by the needs of the patient, the type and severity of the symptoms and the degree of disability.     

Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care

Background  Despite the trend towards making a positive diagnosis of irritable bowel syndrome (IBS), many health care providers approach IBS as a diagnosis of exclusion.
Aim  To summarize available evidence on the diagnostic performance of symptom-based IBS criteria in excluding organic diseases, and of individual signs and symptoms in diagnosing IBS and to additionally assess the influence of sources of heterogeneity on diagnostic performance.
Methods  We searched PubMed and EMBASE and screened references. Studies were selected if the design was a primary diagnostic study; the patients were adults consulting because of non-acute abdominal symptoms; the diagnostic test included an externally validated set of IBS criteria, signs, or symptoms. Data extraction and quality assessment were performed by two reviewers independently. The review adhered to the most recent guidelines as described in the Cochrane Diagnostic Reviewers' Handbook.
Results  A total of 25 primary diagnostic studies were included in the review. The performance of symptom-based criteria in the exclusion of organic disease was highly variable. Patients fulfilling IBS criteria had, however, a lower risk of organic diseases than those not fulfilling the criteria.
Conclusions  With none of the criteria showing sufficiently homogeneous and favourable results, organic disease cannot be accurately excluded by symptom-based IBS criteria alone. However, the low pre-test probability of organic disease especially among patients who meet symptom-based criteria in primary care argues against exhaustive diagnostic evaluation. We advise validation of the new Rome III criteria in primary care populations.     

Irritable bowel syndrome - an evidence-based approach to diagnosis

Irritable bowel syndrome (IBS) represents one of the most common reasons for primary care visits and consultation with a gastroenterologist. It is characterized by abdominal discomfort, bloating and disturbed defecation in the absence of any identifiable physical, radiologic or laboratory abnormalities indicative of organic gastrointestinal disease. IBS is a costly disorder, responsible for significant direct and indirect costs to patients and society. Much of the cost attributed to IBS arises from the time and resources used to establish the diagnosis. Historically IBS has been viewed by many as a diagnosis of exclusion rather than as a primary diagnosis, and many patients with typical symptoms will undergo an extensive array of diagnostic tests and procedures prior to the eventual diagnosis of IBS. Recent reviews addressing the management of such patients have cast doubt on the necessity for this degree of testing. Current best evidence does not support the routine use of blood tests, stool studies, breath tests, abdominal imaging or lower endoscopy in order to exclude organic gastrointestinal disease in patients with typical IBS symptoms without alarm features. Serological testing for celiac sprue in this population may eventually prove useful but validation of studies indicating an increased prevalence of this disease in patients with suspected IBS is needed. The development and refinement of symptom-based criteria defining the clinical syndrome of IBS has greatly facilitated the diagnosis of this condition, which can be confidently diagnosed through the identification of typical symptoms, normal physical examination and the exclusion of alarm features. The presence of alarm features or persistent non-response to symptom-directed therapies should prompt a more detailed diagnostic evaluation dictated by the patient's predominant symptoms.     

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).     

Rationale for using serotonergic agents to treat irritable bowel syndrome.

PURPOSE: The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described. SUMMARY: IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT(4))-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT(3)-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated. CONCLUSION: The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.     

Systematic review: the costs of ulcerative colitis in Western countries

Aliment Pharmacol Ther 31 , 693–707

Summary

Background Early onset and complications such as hospitalization and surgery contribute to the economic burden of ulcerative colitis. Aim To review systematically the literature on costs of ulcerative colitis in Western countries. Methods Studies estimating costs of ulcerative colitis in Western countries were identified using Medline, EMBASE and ISI Web of Science and were rated based on relevance and reliability of estimates. All costs were adjusted to 2008 currency values. A parallel review focused on the impact of disease severity on costs, hospitalizations and surgeries. Results Estimated annual per‐patient direct medical costs of ulcerative colitis ranged from $6217 to $11 477 in the United States and from €8949 to €10 395 in Europe. Hospitalizations accounted for 41–55% of direct medical costs. Indirect costs accounted for approximately one‐third of total costs in the United States and 54–68% in Europe. Total economic burden of ulcerative colitis was estimated at $8.1–14.9 billion annually in the United States and at €12.5–29.1 billion in Europe; total direct costs were $3.4–8.6 billion in the United States and €5.4–12.6 billion in Europe. Direct costs, hospitalizations and surgeries increased with worsening disease severity. Conclusions Ulcerative colitis is a costly disease. Hospitalizations contribute significantly to direct medical costs, and indirect costs are considerable, having previously been substantially underestimated.     

Drug-related morbidity and mortality: updating the cost-of-illness model

OBJECTIVE: To update the 1995 estimate of $76.6 billion for the annual cost of drug-related morbidity and mortality resulting from drug-related problems (DRPs) in the ambulatory setting in the United States to reflect current treatment patterns and costs. DESIGN: For this study, we employed the decision-analytic model developed by Johnson and Bootman. We used the model's original design and probability data, but used updated cost estimates derived from the current medical and pharmaceutical literature. Sensitivity analyses were performed on cost data and on probability estimates. SETTING: Ambulatory care environment in the United States in the year 2000. PATIENTS AND OTHER PARTICIPANTS: A hypothetical cohort of ambulatory patients. MAIN OUTCOME MEASURES: Average cost of health care resources needed to manage DRPs. RESULTS: As estimated using the decision-tree model, the mean cost for a treatment failure was $977. For a new medical problem, the mean cost was $1,105, and the cost of a combined treatment failure and resulting new medical problem was $1,488. Overall, the cost of drug-related morbidity and mortality exceeded $177.4 billion in 2000. Hospital admissions accounted for nearly 70% ($121.5 billion) of total costs, followed by long-term-care admissions, which accounted for 18% ($32.8 billion). CONCLUSION: Since 1995, the costs associated with DRPs have more than doubled. Given the economic and medical burdens associated with DRPs, strategies for preventing drug-related morbidity and mortality are urgently needed.     

Economic burden of irritable bowel syndrome. Proposed strategies to control expenditures

It has been suggested that the annual direct costs for irritable bowel syndrome (IBS) are now around $US41 billion in the 8 most industrialised countries. This paper reviews the data on calculations of direct costs. The true economic burden is unclear, as there are insufficient data on indirect costs other than absenteeism from work and intangible costs cannot be estimated, particularly since presenters with IBS constitute only a subset of the patients with such symptoms in the community. Strategies to reduce direct costs must include physician and patient education, paramedical-based education and therapy, lay support groups, early consideration of psychosocial issues and psychological treatments, avoidance of unnecessary investigations and optimising the doctor-patient relationship. Indirect and intangible costs could be effectively reduced by novel, effective (not only efficacious) therapies.     

Societal costs of underage drinking

OBJECTIVE: Despite minimum-purchase-age laws, young people regularly drink alcohol. This study estimated the magnitude and costs of problems resulting from underage drinking by category-traffic crashes, violence, property crime, suicide, burns, drownings, fetal alcohol syndrome, high-risk sex, poisonings, psychoses, and dependency treatment-and compared those costs with associated alcohol sales. Previous studies did not break out costs of alcohol problems by age. METHOD: For each category of alcohol-related problems, we estimated fatal and nonfatal cases attributable to underage alcohol use. We multiplied alcohol-attributable cases by estimated costs per case to obtain total costs for each problem. RESULTS: Underage drinking accounted for at least 16% of alcohol sales in 2001. It led to 3,170 deaths and 2.6 million other harmful events. The estimated $61.9 billion bill (relative SE = 18.5%) included $5.4 billion in medical costs, $14.9 billion in work loss and other resource costs, and $41.6 billion in lost quality of life. Quality-of-life costs, which accounted for 67% of total costs, required challenging indirect measurement. Alcohol-attributable violence and traffic crashes dominated the costs. Leaving aside quality of life, the societal harm of $1 per drink consumed by an underage drinker exceeded the average purchase price of $0.90 or the associated $0.10 in tax revenues. CONCLUSIONS: Recent attention has focused on problems resulting from youth use of illicit drugs and tobacco. In light of the associated substantial injuries, deaths, and high costs to society, youth drinking behaviors merit the same kind of serious attention.     

The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States

Background: This study evaluated the characteristics, healthcare resource utilization (HCRU), and costs, from the payer perspective, of hepatorenal syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality was assessed as a secondary outcome.

Methods: Patients were identified from claims databases of commercially insured patients (OptumHealth Care Solutions Inc.) in 1998–2014 and Medicare beneficiaries in 2009–2013 (5% Standard Analytic Files). At the time of their first inpatient admission (“index date”) with an HRS diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18–64 and Medicare patients must be aged 65 and older.

Results: A total of 784 commercially insured and 1061 Medicare HRS patients met the sample selection criteria. Patients were disproportionately male (commercial: 63.0%; Medicare: 57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare patients. Within the first 30 days, the average hospital length of stay (LOS) was 12.3 days among commercially insured and 10.8 days among Medicare patients. Based on Kaplan–Meier analyses, 36% of commercially insured and 26% of Medicare patients were readmitted within the next 30 days. During follow-up, many patients received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90?day follow-up were $157,665 for commercially insured and $48,322 for Medicare patients, with 68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of costs), with differences between the populations consistent with lower mortality, higher dialysis rates, and higher transplant rates (both liver and kidney) among the commercially insured. Using US population and prevalence statistics, these results suggest that HRS imposes an annual total direct medical cost burden of approximately $3.0–$3.8 billion to payers over the period.

Conclusions: HRS imposes a significant economic burden.     

Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes.

The impact of Parkinson's disease (PD) and its pharmacologic treatment on health-related quality of life (HRQL) and economic outcomes is reviewed. PD is a chronic and progressive neurologic disorder characterized by specific motor deficits resulting from the degeneration of dopaminergic neurons in the substantia nigra. The cardinal symptoms are tremor, rigidity, bradykinesia, and loss of postural reflexes. PD markedly reduces HRQL and places an economic burden on society of up to $25 billion per year. Patients' inability to move freely and to perform everyday tasks restricts their independence and leads to increased reliance on caregivers and assistive devices. Emotional and psychosocial well-being is also negatively affected. As the disease progresses, the response to levodopa typically decreases and various motor complications develop; these are difficult to treat and result in further declines in HRQL. The economic costs of PD include both direct health care costs (for drugs, physician services, and hospitalization) and indirect costs (for lost worker productivity). Economic analyses of PD and its treatments can help guide effective allocation of health care resources. Various antiparkinsonian agents and formulations, such as extended-release levodopa-carbidopa and pramipexole, have been found to be cost-effective relative to other agents. The newest antiparkinsonian drugs, cathechol-O-methyltransferase inhibitors, also have the potential to improve HRQL and economic outcomes, although more study is needed to confirm this. The total impact of PD and its treatment can be fully appreciated only when HRQL and economic outcomes, in addition to clinical outcomes, are examined.     

Treating Allergic Rhinitis with Second-Generation Antihistamines

Allergic rhinitis afflicts close to 40% of the nation's population and costs more than $1.8 billion a year. The toll exacted by this disorder has been greatly alleviated by nonsedating second-generation antihistamines loratadine, terfenadine, and astemizole. The three agents effectively reduce symptoms without the sometimes intolerable adverse effects of older drugs, but they are not completely equivalent. For example, terfenadine requires twice/day dosing, whereas the others can be given once/day. Astemizole has a slow onset and extremely prolonged duration of action. Both terfenadine and astemizole may have cardiotoxic effects (e.g., torsades de pointes) when serum concentrations rise due to overdosing or drug interactions. Cetirizine, a recently approved second-generation antihistamine, has sedative and anticholinergic effects, although to a lesser degree than the first-generation antihistamines.     

Healthcare costs among patients with hemophilia A treated with factor replacement or bypassing agents

Objective: To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement.

Methods: Claims data from a large US health insurer during 1 January 2006–30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.0) and ≥1 medical or pharmacy claim for bypassing therapy and/or FVIII replacement during 1 January 2007–31 August 2014. The bypassing therapy cohort comprised patients with ≥1 claim for bypassing therapy; all others were assigned to the factor replacement therapy cohort. Post-index hemophilia-related costs were computed as combined health plan plus patient paid amounts for medical claims with hemophilia A diagnosis code or hemophilia therapy procedure code (bypassing therapy, FVIII replacement therapy, desmopressin, antifibrinolytic therapy), as well as pharmacy claims for hemophilia therapy.

Results: The study sample represented 580 patients: 50 (8.6%) in the bypassing therapy cohort (mean age: 38.5?years; mean post-index period: 2.1?years) and 530 (91.4%) in the factor replacement therapy cohort (mean age: 29.3?years; mean post-index period: 2.7?years). Compared with the factor replacement therapy cohort, mean per-patient-per-month hemophilia-related total costs were 4.8-fold higher in the bypassing therapy cohort ($57,232 vs. $11,899), comprising 4.4-fold higher medical costs ($45,911 vs. $10,352) and 7.3-fold higher outpatient pharmacy costs ($11,321 vs. $1547).

Conclusions: Patients with hemophilia A treated with bypassing agents between 2007 and 2014 incurred substantially higher monthly hemophilia-related medical and pharmacy costs than patients treated only with FVIII replacement.     

The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program*

ABSTRACT

Background: Nausea with or without vomiting of pregnancy (NVP) is the most common medical condition in pregnancy. NVP, even with mild symptoms, is associated with costs to society, patients, and the health care system.

Objective: The main objective of this study was to estimate the total direct and indirect costs per woman-week associated with the onset of NVP in Canada from the perspective of society.

Methods: A cost of illness study was performed to estimate the cost per woman-week associated with the onset of NVP in Canada, stratified according to the severity of NVP. Data were collected from 139 pregnant women, who called the Motherisk Program at the Hospital for Sick Children in Toronto. Results are reported in 2005 Canadian dollars.

Results: From the perspective of society, the total cost per woman-week was $132 ($114 indirect and $18 direct costs), $355 ($271 indirect and $84 direct costs), and $653 ($494 indirect and $159 direct costs) for women with mild, moderate, and severe NVP, respectively. Costs increased with increasing severity of NVP.

Conclusions: Nausea and vomiting of pregnancy imposes an economic burden, particularly with respect to productivity losses. Limitations of the study could be potential recall bias, the unavailability of household income and follow-up interviews.     

The economics of coeliac disease: a population‐based study

Aliment Pharmacol Ther 2010; 32: 261–269

Summary

Background Despite increasing prevalence, the economic implications of coeliac disease are just emerging. Aims To assess the impact of coeliac disease diagnosis on healthcare costs and the incremental costs associated with coeliac disease. Methods Administrative data for a population‐based cohort of coeliac disease cases and matched controls from Olmsted County, Minnesota were used to compare (i) direct medical costs 1 year pre‐ and post‐coeliac disease diagnosis for 133 index cases and (ii) 4‐year cumulative direct medical costs incurred by 153 index cases vs. 153 controls. Analyses exclude diagnostic‐related and out‐patient pharmaceutical costs. Results Average total costs were reduced by $1764 in the year following diagnosis (pre‐diagnosis cost of $5023 vs. $3259; 95% CI of difference: $688 to $2993). Over a 4‐year period, coeliac disease cases experienced higher out‐patient costs (mean difference of $1457; P = 0.016) and higher total costs than controls (mean difference of $3964; P = 0.053). Excess average total costs were concentrated among males with coeliac disease ($14 191 vs. $4019 for male controls; 95% CI of difference: $2334 to $20 309). Conclusions Coeliac disease‐associated costs indicate a significant economic burden of disease, particularly for diseased males. Diagnosis and treatment of coeliac disease reduce medical costs of care suggesting an economic advantage to earlier detection and treatment.     

The psychosocial aspects of complementary and alternative medicine

Approximately one in four persons in the United States uses complementary and alternative medicine (CAM). Out-of-pocket costs of CAM rival medical treatment at $21.2-32.7 billion versus $29.3 billion, respectively. Users of CAM tend to have high incomes and high levels of education. They also have medical conditions not easily treated by modern medicine such as chronic pain, poor mental health, human immunodeficiency virus infection, and cancer. The most common therapies are noninvasive (acupuncture, chiropractic, massage), however, consumption of dietary supplements has grown dramatically. Patients often use CAM in addition to modern medicine and are reluctant to discuss CAM with their physicians. Pharmacists' professional approach to science may bias them against CAM therapies. Complementary and alternative medicine use should be included in visit histories and discussed in an objective, nonjudgmental manner to encourage patient disclosure.