Mild-moderate Symptoms Research Articles

The impact of pre‐endoscopy proton pump inhibitor use on the classification of non‐erosive reflux disease and erosive oesophagitis

Factors associated with non-erosive reflux disease (NERD) and erosive oesophagitis (EO) are incompletely understood and the overlap between the two entities is debated. To compare clinical, demographic, and endoscopic findings in a large cohort of NERD and EO patients. After they completed a validated GERD questionnaire, patients who presented for index endoscopy were enrolled and categorized as NERD or EO. Analysis was performed using Chi-square, Mann-Whitney U-test and multivariate logistic regression. A total of 696 GERD patients [455 (65.4%) NERD; 241 (34.6%) EO]; mean age 57 years; 92% men and 82% Caucasian were prospectively enrolled. Using logistic regression, patients on PPI were more likely to be classified as NERD (OR: 3.2; P < 0.001). NERD patients were older (OR: 1.50; P = 0.05), less likely to have nocturnal symptoms (OR: 0.63; P = 0.04) and hiatal hernia (OR: 0.32; P < 0.001). Compared with PPI-naïve NERD patients, those on PPI were more likely to have nocturnal symptoms (69% vs. 29%, P = 0.048) and less likely to have mild-moderate symptoms (63% vs. 79%, P < 0.001) - similar to the EO group. Pre-endoscopy PPI usage contributes significantly to the classification of GERD patients into the NERD-phenotype. NERD patients on PPI therapy demonstrate some features that are significantly different from PPI-naïve patients, but similar to EO patients. This observation supports the notion that some PPI NERD patients are actually healed EO patients, and that an overlap does exist between the GERD phenotypes.

Are PHQ-9 and PHQ-2 Depression Score Cutoffs the Best Cutoffs for Determining Significant Depression in Pts with HF and Mild-Moderate Symptoms?

Introduction: 4 of 9 Pt Health Questionnaire (PHQ)-9 items represent somatic symptoms. Pts with advanced HF may have the same somatic symptoms, causing uncertainty in using original PHQ-9 and PHQ-2 cutoff scores of 10 and 3, respectively to diagnose depression (dep) in HF. Methods: HF pts (N=631; mild HF, n=337; moderate-severe HF, n=294) completed PHQ-9. Original (orig) PHQ-9 and PHQ-2 dep levels were compared by HF status. Alternate (alt) PHQ-9 and PHQ-2 cutoff scores of 15 and 4 were created.

Psychopathology and Clinical Features in an Italian Sample of Patients with Myofascial and Temporomandibular Joint Pain: Preliminary Data

Aim of this study was to provide data on the relationships between psychopathological variables and temporomandibular disorders (TMD). Sixty-three TMD patients were investigated using clinical and anamnestical psychiatric informations and psychopathological measures. Three groups of TMD patients were recruited according to the Research Diagnostic Criteria for TMD guidelines: a group of patients presenting myofascial pain alone (RDC/TMD axis I group I), a group with temporomandibular joint (TMJ) pain alone (RDC/TMD axis I group IIIa, IIIb), and a group presenting both myofascial and TMJ pain. Two secondary groups were identified on the basis of the presence/absence of myofascial pain. The study design provided a psychiatric interview and psychometric assessment including the Symptom Check List-90-Revised (SCL-90-R), the Hamilton Depression Rating Scale (HDRS), and the Hamilton Anxiety Rating Scale (HARS). --Psychiatric evaluation: Myofascial pain patients had higher scores for personal psychiatric history and a history of more frequent psychotropic drug use. --HDRS and HARS: The sample presented scores indicating mild depressive symptoms and moderate anxiety symptoms. --SCL-90-R: The global sample showed acute levels of psychological distress as measured by the GSI score (Global Severity Index). Myofascial pain patients scored higher than TMJ pain patients in the GSI (p = .028), PAR (paranoia; p = .015), PSY (psychoticism; p = .032), and HOS (hostility; p = .034) subscales. TMD patients showed elevated levels of depression, somatization, and anxiety. These characteristics did not differ significantly between patients with myofascial or TMJ pain. Other specific psychopathological dimensions, detected with SCL-90-R, appeared to be closely associated to the myofascial component.

Neurocognitive impairment in middle-aged and older adults with bipolar disorder: Comparison to schizophrenia and normal comparison subjects

Background The frequency, pattern, and correlates of neurocognitive impairment in older patients with bipolar disorder have received little study. We examined neurocognitive abilities in middle-aged and older adults with bipolar disorder to groups with schizophrenia or normal subjects, as well as the relation of neurocognition to clinical characteristics. Method We administered a battery of neurocognitive and clinical measures to older (45–85 years) outpatients with bipolar disorder ( n = 67), schizophrenia ( n = 150), and normal comparison subjects ( n = 85). Within the bipolar group, we assessed the association between neurocognitive performance and psychiatric symptoms, quality of life, and medication status. Results The group with bipolar disorder differed on nearly all neuropsychological tests compared to normal subjects, with medium effect sizes. Bipolar patients as impaired as those with schizophrenia on half of the tests administered, and performed better on the remaining tests, with small effect sizes. Neurocognitive deficits in bipolar disorder group related to lower quality of life, but not to psychiatric symptom severity or duration of illness. Limitations Samples were outpatients with mild-moderate symptoms, and findings may not generalize to acutely ill populations. We lacked data on illness history to examine the cumulative impact of psychopathology. Conclusions Among clinically stable middle-aged and older outpatients, bipolar disorder was associated with substantial neurocognitive impairment, with a pattern that was somewhat distinct from that found in schizophrenia. Deficits in the bipolar group were not related to severity or duration of psychiatric symptoms, but were related to quality of life. Bipolar disorder often involve disabling and enduring cognitive impairments in older outpatients.

γ‐Hydroxybutyrate (GHB) in Humans

Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.

Central motor drive and perception of effort during fatigue in multiple sclerosis

To determine if task performance and fatiguability during repeated low-level contractions of an intrinsic hand muscle differ in a group of MS subjects compared with a control group, and what central changes accompany the development of fatigue and the period of recovery, whether these measures are related to subjective ratings of fatigue or perception of effort. Force of index finger abduction, rating of perceived effort, and motor evoked potential amplitude and silent period duration were measured during and after a 20-min. intermittent submaximal (40%) contraction of the first dorsal interosseous muscle in 23 clinically definite MS subjects with mild-moderate symptoms, and 15 controls. Rating of perceived effort increased at a greater rate in the MS group than in control subjects during exercise, and this was associated with larger increases in both MEP amplitude and silent period duration. Submaximal fatiguing exercise is associated with an enhanced central motor drive and increased perception of effort in MS. MS subjects can increase central drive during fatiguing exercise to a greater degree than controls, but this is associated with greater perceived exertion. These factors may underlie the more general complaint of fatigue experienced by people with MS.

CMV disease in CMV-mismatched renal transplant recipients with prophylactic low dose valaciclovir.

Valaciclovir (VACV) 2 g q.i.d. for 3 months after kidney transplantation has been shown, (Lowance et al., NEJM 1999; 340: 1462-70), to reduce CMV disease from 45 to 16% and rejection from 52 to 26% in CMV-negative (D+R-) recipients. Neurotoxic side effects, however, were frequent, and 5% of the patients experienced hallucinations. We hypothesised that a lower dosage of VACV would prevent CMV disease with fewer CNS side effects. Since September 1998 all CMV-mismatched renal transplant recipients received VACV 1 g t.i.d. for 3 months posttransplantation (PT). The incidence of CMV disease, rejection and neurotoxic side effects during 6 months PT was studied retrospectively in, up to now, 25 patients. 24% (6/25) of the patients developed CMV disease. The mean time for onset of symptoms was 145 days (92-191). Five of the patients had mild-moderate symptoms and recovered after ganciclovir therapy for 3 weeks. One patient was diagnosed with a CMV-associated retinitis on day 191 PT. The rate of biopsy-confirmed acute graft rejection was 32% (8/25). 20% (5/25) of the patients had a serum creatinine of >200 micromol/l after 6 months, including one patient on hemodialysis. CNS adverse effects were not observed. None out of nine patients with basiliximab induction and VACV developed CMV disease. One patient with basiliximab that did not receive VACV, developed a symptomatic CMV-infection. The incidence of CMV disease was lower than in historical controls at our centre, and the time to onset of symptoms was prolonged. Compared to the 8 g VACV/day study, CMV disease and graft rejection was more frequent, but no neurotoxic side effects were observed. A combination with basiliximab induction and VACV 3 g/day shows promising results, but randomised studies are needed for confirmation.

PMA4: AN ECONOMIC PROOF AND APPLICATION THAT FORMULARY RESTRICTIONS WITHIN DRUG CLASSES ALWAYS RESULT IN HIGHER COSTS

Pharmaceutical benefit providers use restrictive formularies to control health care expenditures for drugs. One type of restriction requires the use of one drug before the use of another drug within the same drug. OBJECTIVE: Test the hypothesis that restrictive formularies lower expenditures for pharmaceuticals. METHOD: We use expected utility theory to derive equations for the restrictive and unrestrictive formulary cases where the equations take into account effectiveness (i.e., the probability of attaining treatment goal and not attaining goal), alternatives if treatment fails and costs of each scenario. Administrative costs are assumed zero. We prove mathematically that restrictive formularies within drug classes always cost more. Moreover, even if all drugs in the therapeutic class are equal in effectiveness and equal in cost, the restrictive formulary will still always be more costly than the unrestrictive one. We then allow effectiveness and costs to vary and derive equation to calculate the cost of a restrictive formulary in those cases. We derive the equations for patients with various distributions of baseline severity. Last, we apply the equations and actual effectiveness and cost data to the case of atypical antipsychotics where Ontario and British Columbia Provincial formularies have mandated that risperidone be prescribed before quetiapine or olanzapine. RESULT: The cost of the restrictive status would range from $0.87–0.97 per patient per day with mild symptoms treated with risperidone, $2.65–3.30 for patients with moderate symptoms and $5.14–5.73 for patients with severe symptoms. The range depends on effectiveness rates. Even if all drug costs were equal and the efficacy rates were all 80 percent, the cost per patient per day for the restrictive status of quetiapine would be $0.66–0.71, $1.12–1.41, $1.67–2.26 for risperidone patient with mild moderate and severe symptoms. CONCLUSION: To our knowledge this is the first proof and practical application. Restrictions were removed in both provinces.

Heart failure – from pathophysiology to therapy

Swedberg K et al. (Department of Medicine, Östra University Hospital, Göteborg, Sweden). Heart failure – from pathophysiology to therapy (Minisymposium). J Intern Med 1996; 239: 305–43.Population studies, together with data from clinical records, reveal a range of estimated heart failure prevalence of 1–10%. Estimated incidence rates vary around 1% per annum. In community studies, the five‐year mortality is between 50–60%, while in patients requiring hospital admission, the annual mortality is 10–20% in those with mild–moderate symptoms and as high as 40–60% in severe heart failure.Many definitions of heart failure have been formulated. Making a diagnosis is a complex process. Heart failure is not a diagnosis or even one syndrome, but is a cluster of syndromes. The diagnosis is therefore only part of the assessment process. Essential parts for the diagnosis include symptomatology, objective evidence of important cardiac dysfunction and evaluation of the response to therapy. The cardinal symptom is exertional breathlessness. At present, echocardiography remains the most useful tool for confirming cardiac dysfunction, but determination of atrial natriuretic peptide or magnetic resonance imaging may supersede it. Heart failure has been viewed primarily as an oedematous disorder, in which fluid retention occurs because the heart cannot pump adequate quantities of blood to the kidneys. This model led to the utilization of diuretics for heart failure, but it failed to recognize that heart failure is a chronic progressive disorder that impairs both the quality and quantity of life, even when oedema is adequately controlled.A new model has been developed in which the development and progression of heart failure is viewed as resulting from the interplay of haemodynamic and neurohormonal mechanisms. Both mechanisms support the inotropic state of the heart following an injury to the myocardium, but when sustained for long periods, these mechanisms act to enhance ventricular wall stress, and, thereby, impair ventricular performance. As the heart failure evolves, endogenous mechanisms that are normally activated to control wall stress become exhausted, and peripheral vasoconstriction and sodium retention develop. Unopposed activation of haemodynamic stresses and neurohormonal systems leads to further destruction of myocardium and progression of the underlying disease. The acceptance of this haemodynamic–neurohormonal model has led to the development of vasodilators and neurohormonal antagonists which have been shown to be useful alone – or added to diuretics – in the treatment of heart failure.Non‐pharmacological therapy includes counselling of life style and, for patients with moderate heart failure, light exercise. Within the last decade, pharmacological therapy was improved considerably. Asymptomatic patients with left ventricular dysfunction benefit from acetylsalicylic acid (ASA) and beta‐blockers. In patients with progressive dilatation of the left ventricle and with an established left ventricular dysfunction treatment with angiotensin‐converting enzyme (ACE) inhibitors has beneficial effects on mortality and morbidity.In symptomatic patients and those with clear systolic left ventricular dysfunction in addition to digitalis and diuretics, ACE inhibitors are clearly indicated in addition to ASA. Beta‐blockers may be added but the true benefit is not established. The initiation of both ACE inhibitors and beta‐blockers should be careful and the dose titrated slowly. Antiarrhythmic class I agents should be avoided unless clear indications are present, e.g. life‐threatening arrhythmias. Amiodarone might be considered as an alternative.The prognosis for patients with heart failure remains serious and the search for even better therapies should continue.

Heart failure--implications of the true size of the problem.

We review current knowledge on the true size of the clinical condition known as 'heart failure' in terms of epidemiological information and in relation to the true clinical burden. Population studies, together with data from physician and general practitioner records, reveal a range of estimated heart-failure prevalence of 1-10%. Estimated incidence rates vary from approximately 0-1% per annum. Reasons for variation include age, sex and, possibly, methodology. In community studies, the five-year mortality is between 50-60% while, in patients requiring hospital admission, the annual mortality is 10-20% in those with mild-moderate symptoms, and as high as 40-60% in severe heart failure. While angiotensin-converting enzyme (ACE) inhibitor treatment does significantly improve mortality in all grades of symptomatic heart failure, the annual mortality in severe patients was still 36% in CONSENSUS I. It is obvious that the term 'heart failure' is insufficiently descriptive or specific to be an acceptable label for all patients who might benefit from treatment. As 'clinical' heart failure is often an advanced and irreversible state, studies of its antecedents are important in developing strategies aimed at retarding the progression from the asymptomatic to the symptomatic conditions. The true prevalence of the most common antecedent, left ventricular dysfunction, has received relatively little attention.

Lymphosarcoma of the mandible associated with macroglobulinaemia of Waldenström : SHTEYER A. and MARKITGIU A. Int J. Oral Surg.7 (1978) 585–589

<dm:abstracts xmlns:dm="http://www.elsevier.com/xml/dm/dtd"><ce:abstract xmlns:ce="http://www.elsevier.com/xml/common/dtd" view="all" class="author" id="aep-abstract-id7"><ce:section-title>Publisher Summary</ce:section-title><ce:abstract-sec view="all" id="aep-abstract-sec-id8"><ce:simple-para id="fsabs002" view="all">Cryoglobulinemia is defined as the presence of circulating immunoglobulins (I<ce:inf loc="post">g</ce:inf>) that precipitate at temperatures &lt; 37°C and re-dissolve on re-worming. Such an in vitro phenomenon is detectable in a wide number of chronic infectious and immunological disorders, as well as in some hematological malignancies. This chapter discusses Mixed Cryoglobulinemia (MC) that refers to a distinct clinical syndrome in the absence of other well known systemic or neoplastic disorders. Clinically, MC is characterized by a typical triad—purpura, weakness, arthralgias—and by multisystem organ involvement including chronic hepatitis, membranoproliferative glomeruonephritis (MPGN), peripheral neuropathy, skin ulcers, widespread vasculitis, and less frequently lymphatic and hepatic malignancies. The treatment of MC syndrome is particularly challenging because of its complex etiopathogenesis. For a correct therapeutic approach to hepatitis C virus (HCV)-related MC, one must deal with the concomitance of conflicting conditions: HCV infection, autoimmune, and lymphoproliferative alterations. While asymptomatic patients usually do not need any treatment even in the presence of high levels of cryocrit, patients with mildmoderate symptoms—such as palpable purpura—are particularly sensitive to the smallest variations of daily steroid dosage (1-2 mg).</ce:simple-para></ce:abstract-sec></ce:abstract></dm:abstracts>