Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

Feasibility of a walking workstation to increase daily walking.

OBJECTIVE: The number of calories expended in the workplace has declined significantly in the past 75 years. A walking workstation that allows workers to walk while they work has the potential to increase caloric expenditure. We evaluated whether employees can and will use walking workstations while performing their jobs. METHODS AND PROCEDURES: We studied nurses, clinical assistants, secretaries and appointment secretaries using the StepWatch Activity Monitor System (which accurately measures steps taken at slow speeds) while performing their job functions in their usual fashion and while using the walking workstation. RESULTS: Subjects increased the number of steps taken during the workday by 2000 steps per day (p<0.05). This was equivalent to an increase in caloric expenditure of 100 kcal/day. Subjects reported that they enjoyed using the workstation, that it could be used in the actual work arena and that, if available, they would use it. DISCUSSION: Walking workstations have the potential for promoting physical activity and facilitating weight loss. Several subjects in this study expended more than 200 extra calories daily using such a system. Further trials are indicated.

The treatment of irritable bowel syndrome.

The efforts of clinical researchers, lay organizations and pharmaceutical companies have increased the public profile of irritable bowel syndrome and made it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical diagnosis, which is the foundation of a logical management strategy. This begins with education. Reassurance that no structural disease threatens should be tempered with the reality that symptoms are likely to recur over many years. Patients expect diet and lifestyle advice, even if this is not specific to irritable bowel syndrome. Only a few of those with irritable bowel syndrome see doctors, and even fewer see specialists. Therefore, the treating physician should ascertain the reason for the visit, the patient's fears and the presence of any comorbid illness, such as depression, that might require treatment in its own right. No drug treatment is useful for all of the symptoms of irritable bowel syndrome, and many patients require no drug at all. If used, drugs should target the predominant symptom. Alosetron, a 5-HT3 antagonist, is effective in treating women with irritable bowel syndrome who also have diarrhoea. Tegaserod, a 5-HT4 agonist, is useful for women with irritable bowel syndrome who are constipated. Most patients with irritable bowel syndrome need psychological support. Reassurance, discussion and relaxation techniques can be provided by the family doctor. Difficult psychopathology may require referral to a mental health professional, and the gastroenterologist can settle diagnostic uncertainties. In all cases, successful treatment depends on a confident diagnosis and the strength of the doctor-patient relationship.

Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome.

This consensus document reviews the current status of the epidemiology, social impact, patient quality of life, pathophysiology, diagnosis and treatment of irritable bowel syndrome. Current evidence suggests that two major mechanisms may interact in irritable bowel syndrome: altered gastrointestinal motility and increased sensitivity of the intestine. However, other factors, such as psychosocial factors, intake of food and prior infection, may contribute to its development. Management of patients is based on a positive diagnosis of the symptom complex, careful history and physical examination to exclude 'red flags' as risk factors for organic disease, and, if indicated, investigations to exclude other disorders. Therapeutic choices include dietary fibre for constipation, opioid agents for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain, although the evidence basis for efficacy is limited or in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing study. Treatment should be tailored to patient needs and fears. Novel therapies are emerging, and drugs acting on serotonin receptors have proven efficacy and a scientific rationale and, if approved, should be useful in the overall management of patients with irritable bowel syndrome. Patient and physician education, early identification of psychosocial issues and better therapies are important strategies to reduce the suffering and societal cost of irritable bowel syndrome.

Health-related quality of life in functional GI disorders: focus on constipation and resource utilization.

OBJECTIVE: Functional GI disorders are common in the general population. However, their impact on health status and health resource use in Canada has not been well examined. We describe 1) health-related quality of life in Canadians with functional constipation or other functional GI disorders versus Canadian normative data or those without a functional GI disorder and 2) health resource utilization in subject's self-reporting of constipation. METHODS: An independent research firm was employed to conduct a randomly selected national survey examining GI symptoms and personal health. Household members 18 yr or older were recruited by a random-digit dial technique. Participants were then mailed a questionnaire and data were retrieved by a follow-up phone call. All functional GI disorders were defined using Rome II criteria, and constipation was further defined using self-report. Health-related quality of life was assessed using the Short Form 36. RESULTS: One thousand one hundred forty-nine subjects (49.3% male) with a mean age of 42.2 yr completed the survey. The prevalence of any Rome II functional GI disorder was 61.7%. The rate of functional constipation was 14.9%, whereas that of self-reported constipation was 27.2%. The mean physical and mental component summary and eight subscores of the Short Form 36 were significantly lower (p < 0.05) than Canadian norms for both self-reported constipation and Rome II functional constipation. Subjects with no GI disorder had significantly better Short Form 36 scores than the Canadian norms. The rate of physician visits for constipation was strongly predicted by the physical component of the Short Form 36. Most subjects (66.2%) were satisfied with their current constipation treatment. CONCLUSIONS: Constipation is common in the Canadian population and significantly impairs health-related quality of life. Poor quality of life is an important predictor of health care utilization in these subjects.

Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire.

The Rome II criteria and questionnaires developed to identify functional gastrointestinal disorders have not been evaluated. Our objectives were to determine the prevalence of functional gastrointestinal disorders in Canada, compare our results with data from other published studies, assess concordance of Rome I and Rome II criteria for irritable bowel syndrome, and suggest improvements in the Rome II questionnaire. An independent research firm was employed to conduct a random digit dial national survey, inviting household members > or = 18 years of age to participate in a study examining personal health issues. Subjects recruited by telephone, who agreed to participate, were mailed a questionnaire, and the data were retrieved by a follow-up phone call. The Rome II questionnaire and algorithms were used and where possible Rome I algorithms were also applied. At least one functional gastrointestinal disorder occurred in 61.7% of 1149 respondents (65.6% female versus 57.6% male; P < 0.05). The most prevalent were the functional bowel disorders at 41.6% followed by esophageal disorders at 28.9%. Irritable bowel syndrome prevalence by Rome II and I criteria were 12.1% and 13.5%, respectively (kappa = 0.76). Because the Rome II criteria have added exclusion items that are not present in the Rome I criteria, the prevalence of esophageal, gastroduodenal, and anorectal disorders is lower than the figures from a US market survey. In conclusion, functional gastrointestinal disorders are highly prevalent in Canada, with a significantly higher rate in women. There is substantial agreement between Rome I and Rome II criteria for irritable bowel syndrome. Rome criteria and questionnaire remain works in progress.

Early recognition and treatment of glucose abnormalities to prevent type 2 diabetes mellitus and coronary heart disease.

Striking parallels exist in both risk and protective factors between coronary heart disease and type 2 diabetes mellitus. Patients with insulin resistance are more likely to develop diabetes and coronary heart disease. Better treatment of diabetes may result in less coronary heart disease, although this has not yet been established. Reliance on fasting glucose determinations alone will overlook a substantial number of patients at risk for diabetes and subsequent coronary heart disease. Measurement of glycosylated hemoglobin should be a routine part of screening for patients at risk for diabetes. Patients with glycosylated hemoglobin levels in the high-normal range should be treated more aggressively with diet, exercise, and medication because evidence is good that diabetes can be prevented (or its onset delayed). Patients with borderline elevations of low-density lipoprotein cholesterol concentrations and with high-normal glycosylated hemoglobin levels should be considered for statin therapy, and patients with hypertension with high-normal glycosylated hemoglobin levels should be treated with angiotensin-converting enzyme inhibitors as first-line agents. Studies to determine whether metformin is useful in this population are ongoing.

An epidemiological survey of constipation in canada: definitions, rates, demographics, and predictors of health care seeking.

OBJECTIVES: The prevalence of functional constipation is highly variable among epidemiological surveys and may relate to the definitions applied. We estimated the population prevalence of self-reported, Rome I-defined, and Rome II-defined constipation in Canada and determined the variables that best predicted health care seeking. METHODS: A research firm was employed to conduct a random digit dial national survey, inviting household members at least 18 yr of age to participate in a study assessing personal health issues. The sample was stratified to ensure that each region of Canada was represented. Data collection involved three stages: 1) recruitment of participants by phone, 2) mailing of the questionnaire, and 3) data retrieval through a follow-up phone call. The Rome II questionnaire was used to derive the prevalence of functional constipation using both Rome I and Rome II criteria. RESULTS: Of the 1149 participants, 27.2% self-reported constipation within the past 3 months, and 16.7% and 14.9% had functional constipation according to Rome I and II, criteria, respectively. For all three definitions, the rate for women was close to twice that for men. Approximately 34% of those with self-reported constipation had visited a physician for it, versus 26.3% of Rome II subjects. In a regression model, subjects self-reporting in the past 3 months were more likely to have seen a doctor for their constipation (odds ratio 2.47, p < 0.01) and significantly more women than men (35.6% vs 19.5%, p < 0.05). CONCLUSIONS: Functional constipation and related health care seeking are common in the Canadian population and are strongly determined by the definition used. The Rome II criteria for this disorder seem to be satisfactory, but modifications may be considered to allow for constipated subjects taking laxatives and to increase the number of qualifying symptoms.

Probiotics for irritable bowel syndrome: a light in the darkness?

Probiotics have been used with apparent success for several gut disorders, so it is not surprising they have been tried in the treatment of irritable bowel syndrome (IBS). However, the pathogenesis of this disease is unknown, and opinions about how probiotics might work are speculative. Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating. This possibility deserves further study. It is important though, that future trials employ criteria-identified subjects, be sufficiently powered and strictly double blind, and select a suitable outcome measure. Until state-of-the-art trials of probiotics are available, their use should remain in the experimental arena.

The management of irritable bowel syndrome: a European, primary and secondary care collaboration.

OBJECTIVE: To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS: Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS: The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS: European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.

Constipation: a physiological approach.

The first step in managing a patient with constipation is to understand the precise nature of the complaint. Is the onset recent? What are the frequency and form of the stools, and how much effort is required to defecate? Is constipation steady or alternating as in irritable bowel syndrome? Are there structural, metabolic or pharmacological confounders? Is the patient depressed? Has dietary fibre been tried at a sufficient dose? What are the patient's understanding and beliefs about the symptoms? Has there been sufficient and appropriate investigation? Armed with the answers to these questions, physicians can help most patients through lifestyle, dietary and pharmacological adjustments, along with supplementary fibre. Some patients may require regular doses of an osmotic laxative. Those few that fail these measures should have their transit time estimated while on a high fibre diet; if it is normal, further testing is unlikely to help. The above efforts should be re-emphasized, and reassurance should be offered. Some patients may require a psychological assessment. If transit time is prolonged and the patient may benefit from surgery for colonic inertia or biofeedback for anismus, then colon and anorectal function should be assessed. The decision to perform further tests should be made carefully, and unrealistic expectations should be discouraged. Before surgery is offered, the patient should have the benefit of receiving an expert opinion. Biofeedback helps some patients with isolated anorectal dysfunction.

Placebos: a review of the placebo response.

Placebos have been a component of healing since the beginning. Whether consciously or unconsciously given, they are largely responsible for the success of medicine before randomized trials. Yet, even in this era of "evidence-based medicine," placebos remain enigmatic, and elicit mixed attitudes from divers disciplines. However, our ignorance is not total. There are a few facts to cling to and old myths to dispel. The effect of placebos seems to encompass such disparate elements as anxiety, conditioning, expectation, the healer's persona, and the attachment of meaning to illness. Placebos may obscure as well as illuminate the truth about treatment effectiveness. Moreover, it is easy to confuse their effect with the natural progression of the disease being treated. Those engaged in treatment trials must recognize and manage the reality of placebos rather than attempt to eliminate or disparage them. Factors that might influence the placebo effect such as age, gender, and social circumstances need prospective study. Meanwhile doctors, through honest and compassionate interactions with patients, should strive to maximize their treatments' benefits. This implies confident reassurance and the provision of some meaning to the person's symptoms.

Irritable bowel syndrome in general practice: prevalence, characteristics, and referral.

BACKGROUND AND AIMS: Little is known about the prevalence, symptoms, diagnosis, attitude, and referral to specialists of patients with irritable bowel syndrome (IBS) in general practice. This study aimed to determine these characteristics. METHODS: 3111 patients attending 36 general practitioners (GPs) at six varied locations in and near Bristol, UK, were screened to identify those with a gastrointestinal problem. These patients (n=255) and their doctors were given questionnaires. Six months later the case notes were examined to reach criteria based diagnoses of functional bowel disorders. RESULTS: Of 255 patients with a gastrointestinal complaint, 30% were judged to have IBS and 14% other functional disorders. Compared with 100 patients with an "organic" diagnoses, those with IBS were more often women and more often judged by their GP to be polysymptomatic and to have unexplained symptoms. The majority of patients with IBS (58%) were diagnosed as such by the GP; 22% had other functional diagnoses. Conversely, among 54 patients diagnosed as having IBS by the GPs, the criteria based diagnosis was indeed functional in 91%; only one patient had organic disease (proctitis). More patients with IBS than those with organic disease feared cancer. In most some fear remained after the visit to the doctor. On logistic regression analysis, predictors of referral to a specialist (29% referred) were denial of a role for stress, multiple tests, and frequent bowel movements. CONCLUSIONS: Half the patients with gut complaints seen by GPs have functional disorders. These are usually recognised, and few patients are referred. In IBS, cancer fears often remain, suggesting unconfident diagnosis or inadequate explanation.

Irritable bowel syndrome: a management strategy.

In the development of a management strategy for irritable bowel syndrome (IBS) patients we must consider the great number of people with the condition, most of whom do not consult doctors for it. Furthermore, we must be aware of the hidden agenda of those that do. The cause of IBS is unknown, and consequently cure of this chronic recurrent condition is not likely. Moreover, the disorder is very costly, drawing precious resources from the care of more serious diseases. In this chapter I propose a management strategy based on a firm diagnosis of IBS using a minimum of tests, consideration of the patient's agenda, the use of dietary advice, the strategic use of drugs only in resistant cases, a graded therapeutic response and continuing care. There is no specific treatment. The doctor-patient interaction is most important to allay patients' fears and concerns, assist them with psychosocial difficulties, and provide the caring support known to maximize the 'placebo' effect of any treatment.

Recommendations for the management of irritable bowel syndrome in family practice. IBS Consensus Conference Participants.

To help family physicians manage patients with irritable bowel syndrome (IBS), a consensus conference was convened in June 1997 at which 5 internationally recognized experts in IBS presented position papers on selected topics previously circulated to the conference participants. Five working groups comprising family physicians, gastroenterologists and allied health care professionals from across Canada were then charged with developing recommendations for the diagnosis, patient education, psychosocial management, dietary advice and pharmacotherapy, respectively. An evidence-based approach was used where possible; otherwise, recommendations were made by consensus. The participants concluded that family physicians can make a positive diagnosis of IBS using symptom criteria. The pathophysiology is poorly understood, but motility and sensory disturbances appear to play a role. Neither psychological nor specific dietary factors cause IBS, but both can trigger symptoms. Drug therapy is not recommended for the routine treatment of IBS, but short-term trials of drug therapy may be targeted to predominant symptoms in selected patients. A step-wise, patient-centred approach to management is outlined.

Functional bowel disorders and functional abdominal pain.

The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.