Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ? 0.5 ?C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
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To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period.
A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence).
The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group.
Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario).
Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.
To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives.
In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained.
We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers.
Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.
The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.
40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.
1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio 58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.
The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin.
Comment In: Lancet. 2003 May 31;361(9372):1907; author reply 1907-812788596
Comment In: Lancet. 2003 Feb 22;361(9358):634-512606172
Comment In: Lancet. 2003 May 31;361(9372):1906-7; author reply 1907-812788595
BACKGROUND: One hundred twenty women alcoholics recruited to a treatment program called EWA (Early Treatment for Women With Alcohol Addiction) were studied. The selected women were not previously treated for alcohol abuse. METHODS: The women were followed up by use of a structured personal interview, biomarkers sensitive for alcohol abuse (i.e., glutamyl transpeptidase), and questionnaires, by using defined criteria for abstinence, social drinking, satisfactory drinking outcome, and unsatisfactory drinking outcome. RESULTS: Drinking outcome was good (i.e., total abstinence, social drinking, or satisfactory drinking outcome) for 67% of the women during the total follow-up time, by use of strict criteria for relapse. The results were corroborated by the biomarkers. Similar results were reported from two previously studied groups of women from the same department. However, the frequency of abstinence was higher and social drinking was significantly lower among this sample of women. Daily drinking, the use of sedatives, and a long duration of pretreatment alcohol abuse predicted an unfavorable outcome. However, a long duration of outpatient treatment predicted a good outcome, whereas treatment dropout was related to an unsatisfactory drinking outcome. A majority of the women (96%) rated the treatment experience and the treatment program favorably. The overall good results might reflect the selection of the subjects studied. CONCLUSIONS: Improving treatment program adherence would probably improve outcome for the women with an unsatisfactory drinking outcome.
BACKGROUNDS. A focus on psychiatric rehabilitation in order to support recovery among persons with severe mental illness (SMI) has been given great attention in research and mental health policy, but less impact on clinical practice. Despite the potential impact of psychiatric rehabilitation on health and wellbeing, there is a lack of research regarding the model called the Psychiatric Rehabilitation Approach from Boston University (BPR).
The aim was to investigate the outcome of the BPR intervention regarding changes in life situation, use of healthcare services, quality of life, health, psychosocial functioning and empowerment.
The study has a prospective longitudinal design and the setting was seven mental health services who worked with the BPR in the county of Halland in Sweden. In total, 71 clients completed the assessment at baseline and of these 49 completed the 2-year follow-up assessments.
The most significant finding was an improved psychosocial functioning at the follow-up assessment. Furthermore, 65% of the clients reported that they had mainly or almost completely achieved their self-formulated rehabilitation goals at the 2-year follow-up. There were significant differences with regard to health, empowerment, quality of life and psychosocial functioning for those who reported that they had mainly/completely had achieved their self-formulated rehabilitation goals compared to those who reported that they only had to a small extent or not at all reached their goals.
Our results indicate that the BPR approach has impact on clients' health, empowerment, quality of life and in particular concerning psychosocial functioning.
There are limited head-to-head randomized data on patient-related versus stent-related outcomes for everolimus-eluting stents (EES) and sirolimus-eluting stents (SES).
In the SORT OUT IV (Scandinavian Organization for Randomized Trials With Clinical Outcome IV) trial, comparing the EES with the SES in patients with coronary artery disease, the EES was noninferior to the SES at 9 months.
The primary endpoint was a composite: cardiac death, myocardial infarction (MI), definite stent thrombosis, or target vessel revascularization. Safety and efficacy outcomes at 2 years were further assessed with specific focus on patient-related composite (all death, all MI, or any revascularization) and stent-related composite outcomes (cardiac death, target vessel MI, or symptom-driven target lesion revascularization). A total of 1,390 patients were assigned to receive the EES, and 1,384 patients were assigned to receive the SES.
At 2 years, the composite primary endpoint occurred in 8.3% in the EES group and in 8.7% in the SES group (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.73 to 1.22). The patient-related outcome: 15.0% in the EES group versus 15.6% in the SES group, (HR: 0.95, 95% CI: 0.78 to 1.15), and the stent-related outcome: 5.2% in the EES group versus 5.3% in the SES group (HR: 0.97, 95% CI: 0.70 to 1.35) did not differ between groups. Rate of definite stent thrombosis was lower in the EES group (0.2% vs. 0.9%, (HR: 0.23, 95% CI: 0.07 to 0.80).
At 2-year follow-up, the EES was found to be noninferior to the SES with regard to both patient-related and stent-related clinical outcomes.
PURPOSE: To study the long-term results of implantation of the 3M diffractive multifocal intraocular lens (IOL). SETTING: Eye Department, ASA, Arendal, Norway. METHODS: The study comprised 97 eyes in 72 patients. Follow-up was 8 years. Distance and near visual acuities, refractive results, contrast sensitivity, IOL centration, and neodymium:YAG (Nd:YAG) capsulotomies to treat posterior capsule opacification were evaluated. RESULTS: All patients without ocular pathology achieved a best corrected visual acuity (BCVA) of 0.5 or better (i.e., 98.7% had a BCVA of 1.0 or better). Without correction, 73.8% of eyes had a Jaeger acuity of J3 or better and with distance correction, 92.1%. Emmetropia or within +/-0.25 diopter (D) of it was achieved in 58.8% of eyes. An astigmatic shift of 0.827 D cylinder correction was induced. This shift was mainly against the rule (0.717 D). Contrast sensitivity was reduced with spatial frequencies of 6 to 18 cycles per degree. No need for spectacles was reported by 54.2% of patients and by 68.0% of those with bilateral implantation. For near tasks, 63.9% of patients never used spectacles. The IOLs were well centered or minimally decentered in 99.0% of eyes. Posterior capsule opacification was treated by Nd:YAG laser capsulotomy in 55.7% of eyes, with a mean time between surgery and treatment of 34.0 months +/- 23.2 (SD). CONCLUSION: This long-term study proved the 3M diffractive IOL to be safe and effective despite some reduction in contrast sensitivity at higher spatial frequencies. More than half the patients never wore spectacles; 2 of 3 patients with IOLs in both eyes never wore spectacles. Proper patient selection is crucial.
Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF).
Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function.
Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure.
There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation.
According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure.
To compare the 1-year (previously published) and 3-year objective and subjective cure rates, and complications, related to the use of a collagen-coated transvaginal mesh for anterior vaginal wall prolapse against a conventional anterior repair.
Randomised controlled study.
Six departments of obstetrics and gynaecology in Norway, Sweden, Finland, and Denmark.
A total of 138 women, of 55 years of age or older, admitted for stage =2 anterior vaginal wall prolapse.
The women scheduled for primary anterior vaginal wall prolapse surgery were randomised between conventional anterior colporrhaphy and surgery with a collagen-coated prolene mesh. All patients were evaluated using the Pelvic Organ Prolapse Quantification (POP-Q) assessment before and after surgery. Symptoms related to pelvic organ prolapse were evaluated using the Pelvic Floor Impact Questionnaire (PFIQ-7) and the Pelvic Floor Distress Inventory (PFDI-20).