Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study

Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400 mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p=0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p=0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright (C) 2008 John Wiley & Sons, Ltd.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer`s disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer`s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer`s disease.

Capnography reflects ventilation/perfusion distribution in a model of acute lung injury

Background Changes in the shape of the capnogram may reflect changes in lung physiology. We studied the effect of different ventilation/perfusion ratios (V/Q) induced by positive end-expiratory pressures (PEEP) and lung recruitment on phase III slope (S(III)) of volumetric capnograms. Methods Seven lung-lavaged pigs received volume control ventilation at tidal volumes of 6 ml/kg. After a lung recruitment maneuver, open-lung PEEP (OL-PEEP) was defined at 2 cmH(2)O above the PEEP at the onset of lung collapse as identified by the maximum respiratory compliance during a decremental PEEP trial. Thereafter, six distinct PEEP levels either at OL-PEEP, 4 cmH(2)O above or below this level were applied in a random order, either with or without a prior lung recruitment maneuver. Ventilation-perfusion distribution (using multiple inert gas elimination technique), hemodynamics, blood gases and volumetric capnography data were recorded at the end of each condition (minute 40). Results S(III) showed the lowest value whenever lung recruitment and OL-PEEP were jointly applied and was associated with the lowest dispersion of ventilation and perfusion (Disp(R-E)), the lowest ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) and the lowest difference between arterial and end-tidal pCO(2) (Pa-ETCO(2)). Spearman`s rank correlations between S(III) and Disp(R-E) showed a =0.85 with 95% CI for (Fisher`s Z-transformation) of 0.74-0.91, P < 0.0001. Conclusion In this experimental model of lung injury, changes in the phase III slope of the capnograms were directly correlated with the degree of ventilation/perfusion dispersion.

Adjuncts to Physical Training of Patients With Severe COPD: Oxygen or Noninvasive Ventilation?

BACKGROUND: Previous studies have shown positive effects from noninvasive ventilation (NIV) or supplemental oxygen on exercise capacity in patients with COPD. However, the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated. METHODS: Twenty-eight patients (mean +/- SD age 68 +/- 7 y) with stable COPD (FEV(1) 34 +/- 9% of predicted) undergoing an exercise training program were randomized to either NIV (n = 14) or supplemental oxygen (n = 14) during group training to maintain peripheral oxygen saturation (S(pO2)) >= 90%. Physical training consisted of treadmill walking (at 70% of maximal speed) 3 times a week, for 6 weeks. Patients were assessed at baseline and after 6 weeks. Assessments included physiological adaptations during incremental exercise testing (ratio of lactate concentration to walk speed, oxygen uptake [(V) over dot(O2)], and dyspnea), exercise tolerance during 6-min walk test, leg fatigue, maximum inspiratory pressure, and health-related quality of life. RESULTS: Two patients in each group dropped out due to COPD exacerbations and lack of exercise program adherence, and 24 completed the training program. Both groups improved 6-min walk distance, symptoms, and health-related quality of life. However, there were significant differences between the NIV and supplemental-oxygen groups in lactate/speed ratio (33% vs -4%), maximum inspiratory pressure (80% vs 23%), 6-min walk distance (122 m vs 47 m), and leg fatigue (25% vs 11%). In addition, changes in S(pO2)/speed, (V) over dot(O2), and dyspnea were greater with NIV than with supplemental-oxygen. CONCLUSIONS: NIV alone is better than supplemental oxygen alone in promoting beneficial physiologic adaptations to physical exercise in patients with severe COPD.

High and Low Frequency TENS Reduce Postoperative Pain Intensity After Laparoscopic Tubal Ligation A Randomized Controlled Trial

Background: Transcutaneous electrical nerve stimulation (TENS) is an effective adjunctive therapy for postoperative pain; however, effects of different frequencies Of stimulation have not been systematically investigated. Laparoscopic sterilization (LS) causes significant pain in the early postoperative period and requires substantial postoperative medication. Therefore, we studied the effects of TENS on postoperative pain after LS through placement of Yoon fallopian rings in a prospective, randomized, double-blinded, and placebo-controlled study. Methods: Sixty-four patients undergoing LS for uterine tube ligation were randomly allocated to receive either active TENS or placebo TENS. Postoperative pain was evaluated using a standard I I-point numeric rating scale and the McGill Pain Questionnaire (MPQ)-pain rating index and number of words chosen. Both high frequency (100 Hz) and low frequency (4 Hz) TENS, at strong, but comfortable sensory intensity, were applied for 20 minutes through 4 electrodes placed around the surgical incision immediately after Surgery. Pain was assessed before and after application of TENS when patients were at postanesthesia care unit (PACU). Results: Both high and low frequency TENS significantly decreased postoperative pain intensity when compared with before administration of TENS using the numeric rating scale (P = 0.001), pain rating index (P = 0.001), and number of words chosen (P 0.001) compared with placebo TENS (P = 0.001). TENS in combination with standard pharmacologic analgesic treatment was efficacious for postoperative pain relief after LS. Conclusions: We recommend regular use of multimodal therapy with TENS and analgesic drugs after LS with placement of Yoon rings.

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery

Objective: To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. Methods: Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. Results: The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI) < 18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). Conclusion: Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.

Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients

OBJECTIVE. To evaluate the effectiveness of the oral application of a 0.12% solution of chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients. DESIGN. The study design was a double-blind, randomized, placebo-controlled trial. SETTING. The study was performed in an ICU in a tertiary care hospital at a public university. PATIENTS. Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received chlorhexidine (n = 98) and those who received a placebo (n = 96). INTERVENTION. Oral rinses with chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patient`s stay in the ICU. Clinical data were collected prospectively. RESULTS. Both groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the chlorhexidine and placebo groups. However, patients in the chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]). CONCLUSION. Oral application of a 0.12% solution of chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.

Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas` cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT)

Background Benznidazole is effective for treating acute and chronic (recently acquired) Tryponosoma cruzi infection (Chagas` disease). Recent data indicate that parasite persistence plays a pivotal role in the pathogenesis of chronic Chagas` cardiomyopathy. However, the efficacy of trypanocidal therapy in preventing clinical complications in patients with preexisting cardiac disease is unknown. Study Design BENEFIT is a multicenter, randomized, double-blind, placebo-controlled clinical trial of 3,000 patients with Chagas` cardiomyopathy in Latin America. Patients are randomized to receive benznidazole (5 mg/kg per day) or matched placebo, for 60 days. The primary outcome is the composite of death; resuscitated cardiac arrest; sustained ventricular tachycardia; insertion of pacemaker or cardiac defibrillator; cardiac transplantation; and development of new heart failure, stroke, or systemic or pulmonary thromboembolic events. The average follow-up time will be 5 years, and the trial has a 90% power to detect a 25% relative risk reduction. The BENEFIT program also comprises a substudy evaluating the effects of benznidazole on parasite clearance and an echo substudy exploring the impact of etiologic treatment on left ventricular function. Recruitment started in November 2004, and >1,000 patients have been enrolled in 35 centers from Argentina, Brazil, and Colombia to date. Conclusion This is the largest trial yet conducted in Chagas` disease. BENEFIT will clarify the role of trypanocidal therapy in preventing cardiac disease progression and death.

CHANGES IN FETAL AND MATERNAL DOPPLER PARAMETERS OBSERVED DURING ACUTE SEVERE HYPERTENSION TREATMENT WITH HYDRALAZINE OR LABETALOL: A RANDOMIZED CONTROLLED TRIAL

We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in acute severe hypertension which were randomly allocated to receive either hydralazine or labetalol. Blood pressure and Doppler ultrasound parameters from maternal uterine and fetal middle cerebral and umbilical arteries were assessed during acute severe hypertension and after treatment. A significant reduction in systolic and diastolic blood pressure was observed in both groups. A significant change in Doppler parameters was observed only in pregnant women who received hydralazine: an increase in uterine arteries resistance index. We concluded that both drugs were highly effective in reducing blood pressure in these women. Despite the observed increase in resistance index of uterine arteries associated with hydralazine, the use of hydralazine and labetalol were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. (E-mail: wpmartins@gmail.com) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

Lipid peroxidation and vitamin E in serum and follicular fluid of infertile women with peritoneal endometriosis submitted to controlled ovarian hyperstimulation: a pilot study

Objective: To assess the level of lipid peroxidation (LP) and vitamin E in the follicular fluid and serum of infertile patients, with or without endometriosis. who were submitted to ovulation induction for assisted reproduction procedures. Design: Prospective study. Setting: Assisted conception unit, university hospital. Patient(s): Infertile patients 20 to 38 years of age were selected prospectively and consecutively and were divided into the endometriosis group (17 patients with pelvic endometriosis) and the control group (19 patients with previous tubal ligation or male factor and without endometriosis). Intervention(s): Peripheral blood samples were collected on D1 (before the beginning of the use of gonadotropins), D2 (day of hCG administration), and D3 (day of oocyte retrieval). On D3, follicular-fluid samples free from blood contamination also were collected and stored. Main Outcome Measure(S): Lipid peroxidation was assessed by malondialdehyde quantification by spectrophotometry, and measurement of vitamin E was performed by HLPC. Result(s): On D1, no significant difference in LP was observed between groups. However, vitamin E levels were significantly higher in the control group. On D2, LP levels were significantly higher in the endometriosis group compared with in the control group, and vitamin E levels continued to be significantly higher in the control group. On D3, there was no significant difference in serum and follicular-fluid levels of LP and vitamin E between groups. However, on D3, vitamin E levels were found to be significantly higher in serum than in follicular fluid in both groups, whereas malondialdchyde levels were significantly lower in follicular fluid than in serum only in the control group. Conclusion(s): Before the beginning of ovulation induction, a significant decrease in vitamin E was observed in patients with endometriosis, perhaps because antioxidants are consumed during oxidation reactions. After ovulation induction with exogenous gonadotropins, the group of patients with endometriosis not only presented increased lipid peroxidation but also maintained lower vitamin E levels than the control group, a fact that hypothetically could compromise oocyte quality in endometriotic patients. However, on the day of oocyte retrieval, both serum LP potential and vitamin E levels were found to be similar in the two groups. (Fertil Steril(R) 2008; 90:2080-5. (C) 2008 by American Society for Reproductive Medicine.)

Signs of Temporomandibular Disorders in Migraine Patients: A Prospective, Controlled Study

Objectives: To identify signs of temporomandibular disorders and cervical pain in individuals with episodic and chronic (transformed) migraine (CM), relative to controls without headaches. Methods: In this prospective, controlled, double-blind study, we examined 93 individuals divided in 3 groups: episodic migraine EM, (n= 31), CM chronic migraine (n= 34), and controls without migraine (n= 28). We recorded signs of temporomandibular disorders, and of pain in the neck, after the protocol of Helkimo (1974). We calculated the odds ratio (OR) and confidence intervals (CI) of symptoms as a function of headache status. Data from all groups were paired and compared using the chi(2) test. The level of significance was 5% in 2-tailed tests. Results: Relative to controls, participants with EM and CM were significantly more likely to have tenderness in the masticatory muscles [controls = 28%, migraine = 54%, (OR = 3.0, 95% CI = 1.1-8.9), CM = 73% (OR = 6.9, 95% CI = 2.3-21.2)], and in the temporomandibular joint [controls = 25%, migraine = 61%, (OR = 4.7, 95% CI = 1.5-14.5), CM = 61% (OR = 4.8, 95% CI = 1.6-14.5)]. They were numerically (but nonsignificantly) more likely to have limited lateral jaw movements (CM = 34%; EM = 26%; NP = 18%), joint sounds (CM = 44%; EM = 29%; NP = 28%), and tenderness in neck muscles (CM = 64%; EM = 51%; NP = 35%). Conclusion: In a tertiary care population, individuals with EM and CM are more likely to have tenderness at the temporomandibular joint and on the masticatory muscles, relative to controls. Studies are needed to investigate whether treatment of 1 disorder will improve the other.

Temporomandibular Disorders Are Differentially Associated With Headache Diagnoses A Controlled Study

Objectives: Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. Methods: The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Results: Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [ relative risk (RR) = 7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR = 4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR = 4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (P < 0.0001), migraine (P < 0.0001), and episodic tension-type headache (P < 0.05). TMD severity was also associated with headache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P = 0.001). Painful TMD (P = 0.0034) and grade of TMD pain (P < 0.001) were associated with headache frequency. Discussion: TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study

PURPOSE. To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP). METHODS. Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan. RESULTS. TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group. CONCLUSIONS. TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.) (Invest Ophthalmol Vis Sci. 2011;52:4485-4496) DOI:10.1167/iovs.10-6932

High CO(2)/H(+) dialysis in the caudal ventrolateral medulla (Loeschcke`s area) increases ventilation in wakefulness

Central chemoreception, the detection of CO(2)/H(+) within the brain and the resultant effect on ventilation, was initially localized at two areas on the ventrolateral medulla, one rostral (rVLM-Mitchell`s) the other caudal (cVLM-Loeschcke`s), by surface application of acidic solutions in anesthetized animals. Focal dialysis of a high CO(2)/H(+) artificial cerebrospinal fluid (aCSF) that produced a milder local pH change in unanesthetized rats (like that with a similar to 6.6 mm Hg increase in arterial P(CO2)) delineated putative chemoreceptor regions for the rVLM at the retrotrapezoid nucleus and the rostral medullary raphe that function predominantly in wakefulness and sleep, respectively. Here we ask if chemoreception in the cVLM can be detected by mild focal stimulation and if it functions in a state dependent manner. At responsive sites just beneath Loeschcke`s area, ventilation was increased by, on average, 17% (P < 0.01) only in wakefulness. These data support our hypothesis that central chemoreception is a distributed property with some sites functioning in a state dependent manner. (C) 2010 Elsevier B.V. All rights reserved.

Hypoalgesic effect of the transcutaneous electrical nerve stimulation following inguinal herniorrhaphy: A randomized, controlled trial

We investigated the effect of transcutaneous electrical nerve stimulation (TENS) for inguinal herniorrhaphy postoperative pain control in a prospective, randomized, double-blinded, placebo-controlled study. Forty patients undergoing unilateral inguinal herniorrhaphy with an epidural anesthetic technique were randomly allocated to receive either active TENS or placebo TENS. Postoperative pain was evaluated using a standard 10-point numeric rating scale (NRS). Analgesic requirements were also recorded. TENS (100 Hz, strong but comfortable sensory intensity) was applied for 30 minutes through 4 electrodes placed around the incision twice, 2 and 4 hours after surgery. Pain was assessed before and after each application of TENS and 8 and 24 hours after surgery. In the group treated with active TENS, pain intensity was significantly lower 2 hours (P = .028), 4 hours (P = .022), 8 hours (P = .006), and 24 hours (P = .001) after the surgery when compared with the group that received placebo TENS. Active TENS also decreased analgesic requirements in the postoperative period when compared with placebo TENS (P = .001). TENS is thus beneficial for postoperative pain relief, after inguinal herniorrhaphy; it has no observable side effects, and the pain-reducing effect continued for at least 24 hours. Consequently, the routine use of TENS after inguinal herniorrhaphy is recommended. Perspective: This study presents the hypoalgesic effect of high-frequency TENS for postoperative pain after inguinal herniorrhaphy. This may reinforce findings from basic science showing an opioid-like effect provided by TENS, given that high-frequency TENS has been shown to activate delta-opioid receptors. (C) 2008 by the American Pain Society.