The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener in subjects with type 2 diabetes.

Reducing the workload of the beta cell by inhibiting insulin secretion may provide beneficial effects for patients with type 2 diabetes. The aim of this study was to investigate the effect of NN414, a beta cell selective potassium channel opener in patients with type 2 diabetes. 24 patients were treated for seven days (placebo, 1.5, 4.5, and 10 mg/kg). In accordance with the pharmacological profile a significant and selective inhibition of insulin secretion was observed (1 h post dose). There were no statistically significant effects on overall glycaemic control. Based on OGTT derived parameters a borderline significant improvement in beta-cell function (1st and 2nd phase insulin secretion) was observed from Day 1 to Day 7.

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma.

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.

[Ciprofloxacin in the treatment of hospital-acquired pneumonia: a surveillance study in 676 patients]. / Ciprofloxacin in der Therapie der nosokomialen Pneumonie: Eine Anwendungsbeobachtung bei 676 Patienten.

BACKGROUND: Controlled clinical trials have shown efficacy of high-dose ciprofloxacin for hospital-acquired (HAP) or nosocomial pneumonia. But it has yet to be demonstrated whether this good efficacy also holds true for routine intensive-care patients outside of controlled trials. PATIENTS: In a post-marketing surveillance study at 87 intensive-care units in Germany we analyzed 676 cases of nosocomial pneumonia treated with intravenous ciprofloxacin in a daily dosage of at least 400 mg. RESULTS: 538 (80 %) patients were evaluable for efficacy. Cure or improvement was reported in 76 % of the cases. Clinical success rate was higher in previously untreated patients receiving ciprofloxacin as monotherapy (85.3 %) or in combination with other antibiotics (78.4 %) than in those who received ciprofloxacin as monotherapy (73.1 %) or as combination therapy (69.2 %) after an antibiotic pretreatment. In the 66 patients with Pseudomonas aeruginosa as causal pathogen, clinical success rate was 86.4 %. 32 adverse events classified as possibly or probably related to ciprofloxacin occurred in 3.1 % of patients; all of those were reversible. CONCLUSIONS: Due to the high success rate, even in cases with failed antimicrobial pretreatment, and the favourable risk-benefit ratio of high-dose ciprofloxacin, ciprofloxacin appears to be an attractive choice in the empiric treatment of hospital-acquired pneumonia.

The Quality Improvement for Depression collaboration: general analytic strategies for a coordinated study of quality improvement in depression care.

It is difficult to evaluate the promise of primary care quality-improvement interventions for depression because published studies have evaluated diverse interventions by using different research designs in dissimilar populations. Preplanned meta-analysis provides an alternative to derive more precise and generalizable estimates of intervention effects; however, this approach requires the resolution of analytic challenges resulting from design differences that threaten internal and external validity. This paper describes the four-project Quality Improvement for Depression (QID) collaboration specifically designed for preplanned meta-analysis of intervention effects on outcomes. This paper summarizes the interventions the four projects tested, characterizes commonalities and heterogeneity in the research designs used to evaluate these interventions, and discusses the implications of this heterogeneity for preplanned meta-analysis.

Resolving disparities in antidepressant treatment and quality-of-life outcomes between uninsured and insured primary care patients with depression.

BACKGROUND: Efforts to improve primary care depression treatment should penetrate to vulnerable uninsured populations. OBJECTIVE: To assess a primary care intervention's impact on treatment and quality-of-life outcomes in uninsured and insured depressed patients during the acute treatment phase. RESEARCH DESIGN: Twelve community primary care practices were randomized to 'enhanced' (intervention) and usual care conditions. Physicians, nurses and administrative staff in enhanced care practices received training to improve detection and management of depression. SUBJECTS: In 1996 to 1997, 383 nonelderly depressed patients who were either uninsured or covered by private insurance/Medicaid were enrolled; 343 (89.6%) completed six-month follow-up. MEASURES: Adequate pharmacotherapy (>or=3 months of antidepressants at therapeutic doses); adequate psychotherapy (>or=8 counseling visits); improvement in mental-health-related-quality-of-life (MHQOL), assessed by Mental Component Summary scale for SF-36. RESULTS: Multivariate results showed that 54.6% of uninsured enhanced care (UEC) patients received adequate pharmacotherapy, compared with 14.3% of uninsured usual care (UUC) patients (P = 0.0005); however, receipt of adequate psychotherapy was comparable between these two groups (18.2% UEC, 11.9% UUC; P = 0.42). Intervention effects on insured patients' treatment were modest to minimal. Among usual care patients, the insured had 5.4 points greater improvement in MHQOL at 6 months than the uninsured (12.4 points insured, 7.0 points uninsured; P = 0.02); however, among patients receiving the intervention, the insured and uninsured had comparable MHQOL improvement (12.3 points insured, 11.6 points uninsured; P = 0.76). CONCLUSIONS: The intervention improved antidepressant treatment rates in uninsured patients and helped resolve quality-of-life outcome disparities observed between insured and uninsured patients receiving usual care.

Reliability of the services assessment for children and adolescents.

OBJECTIVE: This study examined the test-retest reliability of a new instrument, the Services Assessment for Children and Adolescents (SACA), for children's use of mental health services. METHODS: A cross-sectional survey was undertaken at two sites. The St. Louis site used a volunteer sample recruited from mental health clinics and local schools. The Ventura County, California, site used a double-blind, community-based sample seeded with cases of service-using children. Participating families completed the SACA and were retested within four to 14 days. The reliability of service use items was calculated with use of the kappa statistic. RESULTS: The SACA- Parent Version had excellent test-retest reliability for both lifetime service use and previous 12-month use. The SACA also had good to excellent reliability when administered to children aged 11 and older for lifetime and 12-month use. Reliability figures for children aged nine and ten years were considerably lower for lifetime and 12-month use. The younger children's responses suggested that they were confused about some questions. CONCLUSIONS: This study demonstrates that parents and older children can reliably report use of mental health services by using the SACA. The SACA can be used to collect currently unavailable information about use of mental health services.

Measuring outcomes of care for adolescents with emotional and behavioral problems.

OBJECTIVES: To validate the prototype Adolescent Treatment Outcomes Module (ATOM), examine its sensitivity to clinical change, and determine its feasibility for administration in routine clinical settings. METHOD: A sample of 67 adolescents, aged 11 through 18, was selected from new patients at two inpatient and two outpatient mental health programs. Adolescents and parents completed the ATOM and validating instruments at intake, 1 week postintake, and again at 6 months. RESULTS: Nine self-report symptoms predicted positive diagnoses of oppositional defiant, conduct, anxiety, and depressive disorders on the basis of structured diagnoses, with sensitivities of 0.7 to 0.8. Test-retest correlations for outcome scales were largely excellent (>0.70). Scales that measured functioning at home, in school, and in the community were moderately correlated in the expected direction with global functioning. Decreases in symptom severity and functional impairment were generally associated with decreases in validating instruments. Administration time averaged 25 minutes for adolescents and 28 minutes for parents. CONCLUSIONS: Both parents and adolescents readily completed the ATOM. Module scales demonstrated excellent reliability and good to fair concurrent validity. The ATOM was able to detect change and its absence.

Improving depression outcomes in community primary care practice: a randomized trial of the quEST intervention. Quality Enhancement by Strategic Teaming.

OBJECTIVE: To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression. DESIGN: Following stratification, 6 of 12 practices were randomly assigned to the intervention condition. Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales. SETTING: Twelve community primary care practices across the country employing no onsite mental health professional. PATIENTS: Using two-stage screening, practices enrolled 479 depressed adult patients (73.4% of those eligible); 90.2% completed six-month follow-up. INTERVENTION: Two primary care physicians, one nurse, and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression. MAIN RESULTS: In patients beginning a new treatment episode, the intervention improved depression symptoms by 8.2 points (95% confidence interval [CI], 0.2 to 16.1; P =.04). Within this group, the intervention improved depression symptoms by 16.2 points (95% CI, 4.5 to 27.9; P =.007), physical role functioning by 14.1 points (95% CI, 1.1 to 29.2; P =.07), and satisfaction with care (P =.02) for patients who reported antidepressant medication was an acceptable treatment at baseline. Patients already in treatment at enrollment did not benefit from the intervention. CONCLUSIONS: In practices without onsite mental health professionals, brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode. Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition. More research is needed to determine how primary care teams can best sustain these redefined roles over time.

Provider choice and utility loss due to selective contracting in rural and urban areas.

An econometric model estimated the disutility of traveling long distances for depression treatment, and simulations calculated the utility loss associated with selective contracting in rural and urban areas. A representative sample of depression patients (n = 106) and all practicing providers (n = 3,710) in Arkansas were identified and the distances between them were calculated. Using discrete choice analysis, patient preferences for provider type and travel distance were estimated. Simulations calculated the utility loss associated with alternative scenarios of selective contracting. Provider type and distance were significant predictors of provider choice. To equate the utility loss associated with selective contracting in rural and urban areas, a slightly higher proportion of rural physicians and a substantially higher proportion of rural mental health specialists must be contracted. To avoid further reductions in geographic access, managed care organizations should contract with a higher proportion of rural providers than urban providers.

The relationship between quality and outcomes in routine depression care.

OBJECTIVE: This longitudinal, nonexperimental study examined whether depression treatment provided in concordance with guidelines developed by the Agency for Healthcare Research and Quality (AHRQ) is associated with improved clinical outcomes. METHODS: The medical, insurance, and pharmacy records of a community-based sample of 435 subjects who screened positive for current major depression were abstracted to ascertain whether depression treatment was received and whether it was provided in accordance with AHRQ guidelines. Regression analyses estimated the impact of guideline-concordant treatment on the change in depression severity and on mental and physical health over a six-month period. An instrumental variables analysis was used to check the sensitivity of the results to selection bias. RESULTS: A total of 106 subjects were treated for depression by 105 different primary care and specialty providers. Sixty percent of the sample had current major depression, and about 40 percent had subthreshold depression. Only 29 percent of the patients received guideline-concordant treatment. For patients with major depression, guideline-concordant care was significantly and substantially associated with improved depression severity but not with improvements in overall mental or physical health. The instrumental variables analysis indicated that the standard regression analysis underestimated the treatment effect by 21 percent. For those with subthreshold depression, guideline-concordant care was not associated with improved outcomes. DISCUSSION AND CONCLUSIONS: This community-based, nonexperimental study found a positive relationship between the quality of care for depression and clinical outcomes for patients with major depression in routine practice settings.

Competing demands from physical problems: effect on initiating and completing depression care over 6 months.

OBJECTIVE AND DESIGN: To evaluate a cohort of patients with major depression to examine the effect of competing demands on depression care during multiple visits over 6 months. PARTICIPANTS AND SETTING: Ninety-two patients with 5 or more symptoms of depression and no recent depression treatment were evaluated by 12 primary care physicians in 6 practices in the usual-care arm of an effectiveness trial of the Agency for Health Care Policy and Research Depression Guidelines. MAIN OUTCOME MEASURE: Treatment was considered to be initiated if the patient reported starting a guideline-concordant antidepressant medication or making a visit for specialty counseling. Treatment completion was defined as either a 3-month course of guideline-concordant antidepressant use or completion of 8 or more specialty counseling visits. RESULTS: Among the 92 patients reporting no recent treatment at study enrollment, 57% reported starting and 17% reported completing a course of guideline-concordant antidepressant medication and or specialty counseling at the 6-month interview. The severity of physical problems among patients with high enthusiasm for depression treatment decreased the odds that patients would initiate depression therapy. Severity of physical problems had no observable effect on completing depression therapy in the group of patients who initiated treatment. CONCLUSIONS: Physical problems compete with depression for attention over multiple visits in untreated patients who are enthusiastic about getting care for their emotional problems. Interventions are needed for this high-risk group, because depression treatment could potentially enhance patients' treatment of their physical problems. Arch Fam Med. 2000;9:1059-1064

Large employers' selection criteria in purchasing behavioral health benefits.

To determine the criteria other than cost large employers use in selecting and monitoring behavioral health benefits, this study interviewed 31 of 44 (70.4%) randomly selected corporations employing at least 5,000 workers. While more than 60% of employers considered administrative efficiency and provider access to be very influential in their selection of behavioral health benefits, only 12.9% (95% confidence interval 0.7%-25.1%) considered clinical outcomes. Employers who considered clinical outcomes in their purchasing decision reported significantly greater satisfaction with the quality and cost of their behavioral health benefits. Following selection, 38.7% of corporations used employee complaints to monitor quality problems in their behavioral health benefits; 3.2% used clinical outcomes. If society expects employers to purchase behavioral health care on the basis of quality as well as cost, more employers need better indicators of quality.

Designing and implementing a primary care intervention trial to improve the quality and outcome of care for major depression.

Complex interventions, which have been shown to improve primary care depression outcomes, are difficult to disseminate to routine practice settings. To address this problem, we developed a brief intervention to train primary care physicians and nurses employed by the practice to improve the detection and management of major depression. Before recruitment began, the research team conducted academic detailing conference calls with primary care physicians and nurses, and provided in-person training with nurses and administrative staff. Administrative staff screened over 11,000 patients before their visits to identify those with probable major depression. Primary care physicians delegated increased responsibility to office nurses, who educated over 90% of patients about effective depression treatment and systematically monitored their progress over time. Early results demonstrate that community primary care practices can rebundle traditional team roles over the short-term to provide more systematic mental health treatment without adding additional personnel. A rigorous evaluation of this effort will reduce time-consuming, expensive, and often unsuccessful efforts to "translate" research intervention findings into everyday practice.

Rural at-risk drinkers: correlates and one-year use of alcoholism treatment services.

OBJECTIVE: The purpose of this study was to identify a community sample of rural and urban at-risk drinkers, to compare them in terms of sociodemographics, access measures and severity of illness, and to study them prospectively to identify rural/urban differences in use of 12-month alcoholism treatment services. METHOD: A brief telephone screening interview of over 12,000 respondents in six southern states identified a sample of at-risk drinkers. A baseline interview was administered to 733 individuals (67% men, 50% rural residents) that obtained information on substance use and psychiatric disorders, psychosocial factors, social support, four dimensions of access to alcoholism treatment services and prior alcoholism service use. Interviews at 6 and 12 months obtained self-reports of subsequent receipt of alcoholism treatment services. RESULTS: We identified modest differences between rural and urban at-risk drinkers. The rural sample was significantly less well-educated and reported significantly less affordability, accessibility and acceptability of some treatment services (p < .05). Rural at-risk drinkers also appeared to possess significantly greater illness characteristics, including more lifetime DSM-IV criteria for alcohol use disorders, more frequent recent alcohol disorders and more chronic medical problems (p < .05). The longitudinal sample comprised 579 participants, of whom 7% reported receiving some form of alcoholism treatment services in the year after the initial interview. In bivariate analysis, rural drinkers in the sample reported greater use of help for their drinking, more use of psychiatrists and more use of inpatient, outpatient and ER treatment settings than did their urban counterparts. However, significant independent predictors of 12-month alcoholism treatment use in multiple logistic regression were female gender (OR = 0.3), greater social support (OR = 2.2) and illness or severity characteristics including recent diagnosis of alcohol dependence (OR = 3.3), social consequences of drinking (OR = 1.7), concurrent medical problems (OR = 2.1) and prior treatment experience (OR = 4.4). CONCLUSIONS: We found modest differences among rural and urban at-risk drinkers and some evidence of greater barriers to treatment and greater illness severity among rural inhabitants. Further research is needed to know whether community interventions with social networks and other interventions to improve social support may help bring at-risk drinkers into treatment in both urban and rural settings as well as provide other support for sobriety.

The role of competing demands in the treatment provided primary care patients with major depression.

OBJECTIVE: To examine whether competing demands explain the appearance of inadequate primary care depression treatment observed at a single visit. DESIGN: A cross-sectional patient survey. PARTICIPANTS AND SETTING: Two hundred forty patients with 5 or more symptoms of depression seeing 12 physicians in 6 primary care practices, representing 77.4% of the depressed patients identified through 2-stage screening of more than 11,000 primary care attenders. MAIN OUTCOME MEASURES: In patients with elevated depressive symptoms, discussing depression as a possible diagnosis in untreated patients, and changing depression management in treated patients. RESULTS: Physicians and patients discussed depression in 46 (47.9%) of 96 untreated patients; physicians changed depression treatment recommendations in 87 (60.4%) of 144 treated patients with current symptoms. Chronic physical comorbidity decreased the odds that physicians and untreated patients discussed depression as a possible diagnosis (odds ratio = 0.66, P = .01). New problems decreased the odds that treatment recommendations would be changed in treated patients who remained depressed (odds ratio = 0.39, P = .05). Physicians and untreated patients were more likely to discuss depression as a possible diagnosis if patients reported antidepressant medication was acceptable (odds ratio = 4.57, P = .01) and less likely to discuss depression if patients reported specialty care counseling was acceptable (odds ratio = 0.33, P = .05). CONCLUSIONS: The attention depression gets during a given medical visit is less associated with the severity of the patient's depressive symptoms than with the number or recency of other problems the patient has. If competing demands provide ongoing barriers to depression treatment, interventions will be needed to assure that patients with chronic physical problems receive high-quality mental health care in the primary care setting.

A primary care intervention for depression.

To assess a guideline-based intervention's impact on depression care provided in rural vs. urban primary care settings, 12 community primary care practices (four rural, eight urban) were randomized to enhanced (i.e., intervention) and usual care study conditions. The study enrolled 479 depressed patients, with 432 (90.2 percent) completing telephone follow-up at six months. Multilevel analytic models revealed that rural enhanced care patients had 2.70 times the odds (P = 0.02) of rural usual care patients of taking a three-month course of antidepressant medication at recommended dosages in the six months following baseline; urban enhanced care patients had 2.43 times the odds compared with their urban usual care counterparts (P = 0.007). Rural enhanced care patients had 3.00 times the odds of rural usual care patients of making eight or more visits to a mental health specialist for counseling in the six months following baseline (P = 0.03). Comparisons of patients in enhanced care practices showed that rural enhanced care patients had 2.00 times the odds (P = 0.12) of urban enhanced care patients of making at least one visit to a mental health specialist for counseling in the six months following baseline and had comparable odds to urban enhanced care patients (odds ratio [OR] = 1.06, P = 0.77) of making eight or more visits to such specialists during that interval. The study's intervention improved the care received by both rural and urban depressed primary care patients. Moreover, the intervention's effect appears to have been greater in rural settings, particularly in terms of increasing depressed rural patients' use of mental health specialists for counseling.

Omeprazole weakly inhibits CYP1A2 activity in man.

BACKGROUND AND OBJECTIVES: Omeprazole is an inducer of human cytochrome P450 1A (CYP1A) enzymes, but shows inhibitory effects on CYP2C19 and CYP3A4. In this study, a potential inhibitory effect of omeprazole on caffeine metabolism, a validated CYP1A2 marker, was examined. METHODS: A randomized, balanced crossover single-dose study was conducted in 16 healthy volunteers comprising 12 extensive (EM) and 4 poor metabolizers (PM) for CYP2C19. All volunteers received a 40 mg omeprazole dose or placebo 0.5 h prior to caffeine 3 mg/kg body weight. Six EMs were re-tested with 80 mg of omeprazole. In vitro, effects of omeprazole on caffeine N3-demethylation were determined in human liver microsomes. RESULTS: In vivo, non-parametric point estimates (90% confidence intervals) for the ratios of caffeine pharmacokinetics with/without co-administration of the 40 mg omeprazole dose were: AUC 1.08 (1.04 - 1.13), MRT 1.09 (0.99 - 1.19), and plasma ratio of paraxanthine/caffeine 6 h post-dose 0.91 (0.80 - 1.00). Inhibition of caffeine N3-demethylation by omeprazole was slightly more pronounced in PM than in EM of CYP2C19. Estimates for the 80 mg omeprazole dose were: AUC 1.12 (1.05 -1.18), MRT 1.18 (1.07 - 1.30), and paraxanthine/caffeine ratio 0.83 (0.74 -0.94). In vitro, omeprazole was mainly a competitive CYP1A2 inhibitor with K(i) values of around 150 microM. CONCLUSIONS: Omeprazole exerts a concentration-dependent inhibition of CYP1A2 activity in man. However, even after single oral doses up to 80 mg, this effect is weak and without clinical relevance.