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High prevalence of occult endobronchial malignancy in high risk patients with moderate sputum atypia.

Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects.

Aged↗

Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children.

As part of a randomized clinical trial that compared three different analgesic dosing regimens ( Sutters et al., 2004 ), the purpose of this study, in children who underwent tonsillectomy, was to determine whether around-the-clock (ATC) dosing of acetaminophen with codeine, compared with as-needed (PRN) dosing, increased the frequency of moderate-to-severe opioid-related side effects (i.e., daytime sedation, lightheadedness, nightmares, nausea, vomiting, and constipation) in the first 3 days after surgery. Because no differences were found in pain intensity scores and in the amount of analgesic administered between the two ATC groups (i.e., with and without coaching), for these analyses, the two groups were combined ( n = 52) and compared with the PRN group ( n = 28). Each side effect was recoded into a dichotomous response (i.e., 0 = did not have symptoms or had slight symptoms; 1 = symptoms that were moderate, severe, or very severe) to provide an adequate sample size in each cell for the statistical analyses. No differences were found in the frequency of moderate-to-severe side effects between the ATC and PRN groups at any of the postoperative assessments. The number of children who reported moderate-to-severe daytime sedation decreased over time in both the PRN ( p = .02) and ATC groups ( p = .01). Children in the ATC groups reported a statistically significant decrease over time in vomiting ( p = .001) and feeling lightheaded or dizzy ( p = .003), and a significant increase in constipation ( p = .018). Except for daytime sedation, changes, over time, in the frequency of moderate-to-severe side effects were not observed in the PRN group.

Acetaminophen↗

Intra-articular morphine 5 mg after knee arthroscopy does not produce significant pain relief when administered to patients with moderate to severe pain via an intra-articular catheter.

BACKGROUND AND OBJECTIVES: Intra-articular (IA) morphine for postoperative analgesia after knee arthroscopy is controversial. The IA catheter technique for test drug administration allows baseline pain assessment before inclusion. Results from one such randomized controlled trial (RCT) in patients with moderate to severe pain have shown equal effects of IA saline with or without morphine 2 mg. However, the IA catheter technique may have an unintended placebo effect. The aims of this placebo-controlled RCT were (1) to compare the analgesic effect of IA saline 1 mL (placebo) with morphine 5 mg given through an IA catheter and (2) to analyze the impact on pain of immediate or delayed removal of the IA catheter. METHODS: Sixty patients operated under general anesthesia had an IA catheter inserted at the end of arthroscopy. Patients who reported moderate or severe postoperative pain during the following hour were randomized to IA saline 1 mL (placebo) or IA morphine 5 mg and to immediate or delayed removal of IA catheter. RESULTS: Forty of 60 patients (67%) developed moderate to severe pain within 1 hour. In addition, 5 patients experienced intolerable pain and were excluded. Significantly more women (24/26) than men (26/39) reported at least moderate pain (P = .018) during the first hour after surgery. There were no differences between IA morphine 5 mg and placebo in pain intensity or pain relief at any time during the 48-hour observation period. There was no detectable effect on pain intensity of early compared with late removal of the IA catheter. CONCLUSIONS: IA morphine 5 mg does not produce clinically significant pain relief in patients with moderate or severe pain after knee arthroscopy.

Adult↗

Cardiac surgery in moderate to end-stage renal failure: analysis of risk factors.

BACKGROUND: The incremental surgical risk caused by different categories of renal failure is not well defined. METHODS: Data from 159 patients with moderate to end-stage renal dysfunction, who had consecutive operations using cardiopulmonary bypass, were included in a multivariate analysis of morbidity and survival. Ninety-nine patients had preoperative serum creatinine levels (PSCL) of 1.9 to 2.5 mg/dL (moderate), 36 had PSCL higher than 2.5 mg/dL and were not dialysis dependent (severe), and 24 required chronic dialysis (end-stage dysfunction). RESULTS: Operative mortality was 4% with moderate dysfunction and compared favorably with 16.7% in severe and 8% in end-stage dysfunction (p < 0.05). Independent predictors of death were severe non-dialysis-dependent renal dysfunction (p < 0.05), diabetes (p < 0.05), and cardiopulmonary bypass time (p < 0.01). Severe renal dysfunction (p < 0.01) and diabetes (p < 0.01) also predicted pulmonary and neurologic morbidity. Freedom from late death at 4 years was 82% +/- 5% with moderate, 49% +/- 10% with severe, and 60% +/- 10% with end-stage dysfunction (p < 0.01). Time to late death was adversely affected by severe (p < 0.05) and end-stage dysfunction (p < 0.01). Persistent improvement of symptoms was observed in all subgroups. CONCLUSIONS: Satisfactory early and late surgical outcomes may be expected in patients with moderate renal failure, but outcomes are often poor with severe non-dialysis-dependent and end-stage renal dysfunction.

Aged↗

Variation of ictal electroencephalographic regularity with low-, moderate-, and high-dose stimuli during right unilateral electroconvulsive therapy.

BACKGROUND: Previous work has demonstrated changes in electroencephalographic (EEG) ictal morphology during electroconvulsive therapy (ECT) as stimulus intensity is increased from barely suprathreshold to moderately suprathreshold. Our study reports on the reactivity of seizure regularity ratings in 11 subjects receiving right unilateral (RUL) ECT as the stimulus is varied over a wider range of intensities from low to medium, then high dose. METHODS: The stimulus intensity of all 11 subjects was first increased from barely suprathreshold to moderately suprathreshold, and then randomized to either stay at a moderately suprathreshold dose or increase to a high dose. The regularity of the EEG ictal discharge was visually measured on a seven-point scale. RESULTS: We found that seizure regularity increases as the stimulus intensity moves from the barely suprathreshold to the moderately suprathreshold dosage, but did not increase further when the stimulus increased to a high dose. CONCLUSIONS: These results suggest that EEG regularity is unlikely to distinguish moderately suprathreshold from markedly suprathreshold stimuli during RUL ECT.

Aged↗

Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats.

BACKGROUND & AIMS: Ghrelin is an orexigenic hormone secreted by the stomach. Increased plasma ghrelin concentration was reported during diet-induced weight loss in obese humans, suggesting that ghrelin contributes to adaptive increment in appetite associated with caloric restriction. Leptin reduces spontaneous food intake and body weight in rodents. The current study tested the hypothesis that increased plasma leptin prevents the potential increase in plasma ghrelin concentration during moderate caloric restriction in lean rats. METHODS: Six-month-old male rats (body weight, 367 +/- 9 grams) were randomly assigned to one of the following treatments (8 rats each) for 1 week: (1) leptin subcutaneous infusion to induce moderate hyperleptinemia and moderate caloric restriction (-26% of ad libitum), (2) vehicle infusion and pair feeding, and (3) vehicle infusion and ad libitum feeding. RESULTS: Leptin-treated (-19 +/- 5 grams) and pair-fed (-19 +/- 2) rats lost weight compared with ad libitum-fed rats (-3 +/- 1, P < 0.05). Compared with control (6.8 +/- 0.7 ng/mL), plasma leptin was higher in leptin-treated (18.6 +/- 0.9 ng/mL, P < 0.01) rats and lower in pair-fed rats (4.3 +/- 0.4 ng/mL, P < 0.05). Plasma ghrelin was substantially higher in calorie-restricted than control rats (2505 +/- 132 pg/mL vs. 1790 +/- 134 pg/mL, P < 0.01), and leptin treatment (1625 +/- 117 pg/mL) completely prevented this change. Plasma ghrelin concentration was negatively correlated with body weight changes in calorie-restricted and control (r = -0.75, P < 0.01) but not in leptin-treated rats (P > 0.8). CONCLUSIONS: Moderate hyperleptinemia prevents an increase of plasma ghrelin during moderate short-term caloric restriction. Satiety-inducing effects of leptin include suppression of gastric orexigenic signals and disruption of a potential feedback mechanism between body weight changes and plasma ghrelin in lean adult rats.

Animals↗

The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial.

The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.

Anticholesteremic Agents↗

Efficacy of budesonide in moderate to severe asthma.

BACKGROUND: The worldwide prevalence of asthma is increasing by approximately 50% per decade. Budesonide is one of several inhaled corticosteroids available for the treatment of asthma and has been extensively evaluated in clinical trials. OBJECTIVE: This article reviews the published literature on the efficacy of budesonide in the management of adult and pediatric patients with moderate to severe asthma and compares budesonide with other inhaled corticosteroids and nonsteroidal treatment options. METHODS: All controlled, randomized studies in patients with moderate or severe asthma were considered for inclusion. Relevant studies were identified through a MEDLINE search of the period from 1980 to 2000 using the terms budesonide plus efficacy, with or without the termsfluticasone, mometasone, and beclomethasone. The manufacturer's reference database was used to identify additional publications. RESULTS: Budesonide is associated with a dose-response effect in adults and children with moderate to severe asthma. The data on budesonide are in line with the current recommendation for a high starting dose of inhaled corticosteroid (800 microg/d), followed by downward titration to the minimal effective dose. Budesonide administered by Turbuhaler (AstraZeneca Pharmaceuticals LP, Wilmington, Del) dry-powder inhaler (DPI) was effective at a significantly lower dose than beclomethasone dipropionate (BDP) administered by pressurized metered-dose inhaler (pMDI) (P = 0.009), whereas its efficacy was similar to that of BDP delivered by hydrofluoroalkane pMDI and that of fluticasone propionate administered by DPI. Inhaled budesonide therapy was shown to be oral corticosteroid sparing in patients with severe asthma, thus reducing the total corticosteroid dose and the risk of systemic side effects. Pulmicort Respules (AstraZeneca), a nebulized formulation, was effective in the treatment of moderate to severe asthma in patients aged > or =12 months. CONCLUSIONS: Once- or twice-daily administration of budesonide delivered via the Turbuhaler and Pulmicort Respules systems has been shown to be well tolerated and efficacious in populations with moderate to severe asthma.

Adult↗

A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.

We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.

Amino Acids↗

[Factors associated with the moderately severe stage of Alzheimer's disease: first results of the REAL.FR study].

OBJECTIVE: Most studies of Alzheimer's disease deal with the mild to moderate stages of the disease. However the great majority of cases evolve toward a stage of marked severity which can last many years. The few studies of severe dementia that have been carried out have included institutionalized patients. The aim of this study is to describe associated factors with a moderately severe Alzheimer's disease in a French community dwelling patients. METHODS: Initial data from a French cohort Study of Alzheimer's patients (REAL.FR: Réseau sur la maladie d'Alzheimer français) were analysed. These included sociodemographic and medical factors and measures of cognitive and non cognitive performance. We compared two groups according the stage of the disease: moderately severe patients (Mini Mental Status score < 15) and mild to moderate patients (Mini Mental Status score > or = 15). RESULTS: Moderately severe stage of disease was independently related to age (OR: 0.35; 95% CI: 0.16-0.78 for patient aged between 75-80 years compared to patient < or = 75 years), low educational level (non-obtention of french certificate of primary education, OR: 2.43; IC à 95%: 1.28-4.59) and disability to perform activities of daily living (OR: 3.35; 95% CI: 1.62-6.93). After multivariate analysis, there was no difference between the 2 groups for the other factors like behavioral symptoms. CONCLUSIONS: Severe dementia represents major medical and socio-economical problem. Better knowledge of the natural history of the severe stage of the disease is necessary for better clinical practice.

Aged↗

Long-term effects of rivastigmine in moderately severe Alzheimer's disease: does early initiation of therapy offer sustained benefits?

Goals of the study included evaluating the long-term efficacy of rivastigmine in Alzheimer's disease (AD) patient categories stratified by baseline dementia severity, and post hoc investigation of particular benefits of early initiation of rivastigmine treatment in moderately severe AD. Both rivastigmine-treated groups (originally randomized to 1-4 or 6-12 mg/day) experienced significantly smaller declines in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores from baseline than the projected placebo group after 52 weeks. Patients receiving rivastigmine from Day 1 experienced significantly less decline compared with patients originally receiving placebo and then initiating rivastigmine treatment after a 6-month delay. Furthermore, cognitive benefits were more robust in patients with moderately severe disease compared with previous reports in mild to moderately severe AD. Findings suggest that early treatment with rivastigmine 6-12 mg/day is associated with sustained long-term cognitive benefits in patients with moderately severe AD. The results support the value of early treatment of AD patients, particularly those with moderately severe AD.

Aged↗

Health and productivity of traditionally managed Djallonke sheep and West African dwarf goats under high and moderate trypanosomosis risk.

Trypanosome infections, packed red cell volume levels (PCV), body weight and nematode faecal egg counts of village-based small ruminants were monitored in two areas in The Gambia with either moderate or high trypanosomosis risk for 24 and 30 months respectively. Outflows from the flock and new-born animals were recorded and data on housing and management were compiled. Reported mortality rates were higher in goats than in sheep, but for both species highest in the moderate risk area. The peak of trypanosome infections lagged the peak of tsetse densities by 1-3 months in both areas. Trypanosoma vivax was the predominant species found in the infected animals, followed by T. congolense. Trypanosome prevalence was, in general, higher in sheep than in goats but only significantly higher during Year 1 in the moderate risk area. Trypanosome infection reduced the PCV level significantly and seasonal effects indicated significantly lower PCV levels during the rains. Trypanosome infection significantly depressed weight gain in both species at periods where infection rates were highest. In both species considerably lower weight gains were observed during the rainy season. Abortion rates were higher in goats than in sheep in both study sites, and highest in the high-risk site. Trypanosome infection in ewes in the high risk area increased lamb mortality significantly but had no effect on birth weights, nor on growth rates up to 4 months. Offspring mortality up to 4 months was generally high at both sites. Trypanosome infection in the dam between 3.5 to 7 months post parturition significantly increased parturition interval in both species. Peak faecal egg output occurred at the end of the rainy season and was highest for both species in the moderate risk site. Poor grazing management was found responsible for a seasonal nutritional constraint. Based on these results, these breeds of sheep and goats can be considered as trypanotolerant since they are able to remain productive under high and moderate levels of trypanosome challenge. Nevertheless, trypanosomosis affected their health and production level as shown by reduced PCV levels, depressed weight gains, longer parturition intervals and higher lamb mortality. In addition, during the rains, helminth infections and poor management leading to nutritional constraints had also a negative impact on health and production and therefore influenced the innate resilience to trypanosomosis in those indigenous breeds. Adaptations in management may have an equal impact as certain disease control measures to improve biological and economical returns from small ruminants in tsetse infested rural areas.

Animal Husbandry↗

[Trial of labor in moderate pelvic dystocia at Dakar University Teaching Hospital].

OBJECTIVE: To study frequency of moderate pelvic dystocia, to evaluate the diagnosis value of clinical pelvic evaluation and prognosis of trial labor with only clinical monitoring. MATERIAL AND METHOD: This is a prospective, exposed and non-exposed study concerning 296 women selected among deliveries presenting moderate pelvic dystocia recorded at Dakar University Teaching Hospital from February 1st 2001 to July 31 2002. Trial labor was undertaken in 148 patients; the control group was chosen among women who underwent prophylactic caesarean section and had no other risk factors of maternal and perinatal complications. Pearson's chi-square test was used or statistic analysis with p value 5% and test of Kappa. RESULTS: Moderate pelvic dystocia was observed 5.3 per 100 deliveries. The most common epidemiological profile was primipara, young age (mean 24 years), height 161 cm (mean), 38-week pregnancy (mean). Clinical evaluation had good diagnosis value comparable with the radiological pelvimetry. Trial labor was undertaken in 148 women, 109 trials (73.6%) were successful; vaginal delivery rate was 27% in women with moderate pelvic dystocia. There were no maternal deaths, maternal morbidity was 4% in trial labor patients and 2.7% in prophylactic caesarean section patents (mainly infection). Post-natal mortality was 7.4% after trial of labour versus 4.1% of newborn child after prophylactic caesarean. CONCLUSION: These results confirm that trial of labor on moderate pelvic dystocia should be the rule whenever possible, even when only clinical monitoring is available.

Adult↗

Is carotid endarterectomy cost-effective in symptomatic patients with moderate (50% to 69%) stenosis?

OBJECTIVE: Recently published data from the North American Carotid Endarterectomy Trial revealed a benefit for carotid endarterectomy (CEA) in symptomatic patients with moderate (50% to 69%) carotid stenosis. This benefit was significant but small (absolute stroke risk reduction at 5 years, 6.5%; 22.2% vs 15.7%), and thus, the authors of this study were tentative in the recommendation of operation for these patients. To better elucidate whether CEA in symptomatic patients with moderate carotid stenosis is a proper allocation of societal resources, we examined the cost-effectiveness of this intervention. METHODS: A decision-analytic Markov process model was constructed to determine the cost-effectiveness of CEA versus medical treatment for a hypothetical cohort of 66-year-old patients with moderate carotid stenosis. This model allowed the comparison of not only the immediate hospitalization but also the lifetime costs and benefits of these two strategies. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year saved. We assumed an operative stroke and death rate of 6.6% and a declining risk of ipsilateral stroke after the ischemic event with medical treatment (first year, 9.3%; second year, 4%; subsequent years, 3%). The hospitalization cost of CEA ($6,420) and the annual costs of major stroke ($26,880), minor stroke ($798), and aspirin therapy ($63) were estimated from a hospital cost accounting system and the literature. RESULTS: CEA for moderate carotid stenosis increased the survival rate by 0.13 quality-adjusted life years as compared with medical treatment at an additional lifetime cost of $580. Thus, CEA was cost-effective with a CER of $4,462. Society is usually willing to pay for interventions with CERs of less than $60,000 (eg, CERs for coronary artery bypass grafting at $9,100 and for dialysis at $53,000). CEA was not cost-effective if the perioperative risk was greater than 11.3%, if the ipsilateral stroke rate associated with medical treatment at 1 year was reduced to 4.3%, if the age of the patient exceeded 83 years, or if the cost of CEA exceeded $13,200. CONCLUSION: CEA in patients with symptomatic moderate carotid stenosis of 50% to 69% is cost-effective. Perioperative risk of stroke or death, medical and surgical stroke risk, cost of CEA, and age are important determinants of the cost-effectiveness of this intervention.

Aged↗

Economic impact of using mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in the UK.

This study modelled the economic impact of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in the UK, as well as the costs related to discontinuation of antidepressant treatment. Decision models of the management of moderate and severe depression were developed from clinical trial data, resource use obtained from interviews with general practitioners and psychiatrists, and published literature, and were used to estimate the expected direct National Health Service (NHS) costs of managing a patient with moderate or severe depression. The expected cost of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment, irrespective of the initial treatment, was estimated to be pounds sterling 206 (range pounds sterling 50 to pounds sterling 504) over five months. Using mirtazapine instead of amitriptyline for seven months increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%) and reduces the expected direct NHS cost by pounds sterling 35 per patient (from pounds sterling 448 to pounds sterling 413). Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for an additional cost to the NHS of pounds sterling 27 per patient (from pounds sterling 394 to pounds sterling 420). In conclusion, this study suggests that mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine in the management of moderate and severe depression in the UK.

Adolescent↗

Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.

Amitriptyline↗

Designing a community study of moderately to severely disabled older women: the Women's Health and Aging Study.

PURPOSE: This paper reports on the design of a community-based study focusing on the effects of prevalent and incident disease and other modifying influences, on changes in functioning among moderately and severely disabled elderly women over a 3-year period [the Women's Health and Aging Study (WHAS)]. METHODS: An approach to conceptualizing and assessing disability which captured functional difficulty across a broad range of activities and tasks was developed, tested on existing national data, and used, in the form of a brief screening instrument, to identify moderately to severely disabled elderly women in a large community sample representative of women 65 and older. Women meeting study criteria were recruited for a baseline interview, a 3-hour in-home clinical exam, as well as follow-up interviews and physical performance tests at 6-month intervals for three years. RESULTS: Prevalence of moderate to severe disability among the screened population proved similar to that expected from analysis of national data (about one-third). The screening interview response rate was 78%, and 71% of women eligible by disability criteria participated. Only women completing both the baseline interview and clinical exam were counted as respondents. Analysis of characteristics of participants and nonparticipants indicated no selection bias related to levels of disability. However, education, race, and age were associated with participation. Women with some college education, black women, and younger women were more likely to participate. CONCLUSIONS: The approach used to identify and recruit moderately to severely disabled elderly women in the WHAS is both feasible and applicable to other community-based research where inclusion of elderly people with moderate to severe disability across several areas of functioning is an objective. Other aspects of study design, such as use of proxy respondents, will also affect recruitment of individuals with impaired functioning into epidemiologic studies.

Activities of Daily Living↗

A comparison of the effects on bispectral index of mild vs. moderate hypothermia during cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Bispectral Index correlates with depth of hypnosis in adult patients. Bispectral index monitoring has been separately examined and validated during both mild and moderate hypothermic cardiopulmonary bypass. However, the effect on bispectral index of these two differing cardiopulmonary bypass temperature regimes has not previously been compared, particularly with the use of volatile anaesthetic agents. METHODS: Following Institutional Ethics Committee approval and informed consent, 30 patients undergoing coronary artery bypass grafting had additional bispectral index monitoring. Sixteen patients had mild hypothermic bypass (32-34 degrees C), and 14 had moderate hypothermic bypass (28-30 degrees C). Anaesthesia was standardized, and was maintained with enflurane throughout surgery. Scores were recorded at 14 specific event-related time points during surgery. RESULTS: This study has demonstrated that in this adult population, a relationship exists between bispectral index score and temperature throughout the duration of cardiac surgery, which included mild or moderate hypothermic cardiopulmonary bypass. It also demonstrated that patients which were categorized as having received moderately hypothermic cardiopulmonary bypass had lower bispectral index scores than those patients who received mild hypothermic cardiopulmonary bypass, at time points corresponding approximately with median steady-state bypass temperature, pre-re-warming and early re-warming periods. CONCLUSIONS: Moderate hypothermic cardiopulmonary bypass has lower bispectral index scores when compared to mild hypothermic cardiopulmonary bypass, at a steady state of inspired enflurane. This may reflect an actual increase in the depth of hypnosis. However, as this study did not address the physico-chemical changes of the volatile agent or the accuracy of the bispectral index algorithm at lower temperatures, we would not advocate a change in practice based solely on this report.

Aged↗