Is it time for home treatment of pulmonary embolism?

Acute pulmonary embolism (PE) is a frequent cause of death, but not all patients are at high risk of an adverse early outcome. It has been proposed that selected patients may be considered for early discharge and home treatment, but it was only recently that improved risk assessment strategies permitted advances in the identification of low-risk PE. Clinical prediction rules, such as the Pulmonary Embolism Severity Index (PESI), and laboratory biomarkers, particularly natriuretic peptides and cardiac troponins, appeared capable of excluding severe PE and serious comorbidity. Recently, two randomised trials and two prospective cohort studies investigated the feasibility and safety of outpatient treatment. All excluded patients with haemodynamic instability and serious comorbidity, but only one trial used a validated clinical score (PESI) for patient inclusion, and only one cohort study employed a biomarker test. Overall, 90-day outcome was favourable and the results appear promising. To optimise patient selection, future trials will need to test simplified clinical scores combined with high-sensitivity biomarker assays, and it will have to be determined whether echocardiography and/or compression ultrasonography are also required before discharge. Furthermore, ongoing trials will show whether new oral anticoagulants are a safe and cost-effective option for managing patients out of hospital.     

α-Blockade and thiazide treatment of hypertension A double-blind randomized trial comparing doxazosin and hydrochlorothiazide

This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the α₁ antagonists, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I—Baseline; Phase II—Monotherapy Titration; Phase III—Combination Therapy Titration; and Phase IV—Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects.Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (−19 and −16 mm Hg); HCTZ (−22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.     

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial

Background & Aims

Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta.

Methods

Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available.

Results

Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL.

Conclusions

Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.     

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors： Randomized placebo-controlled trial

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.     

Efficacy of pramipexole in the treatment of Parkinson's disease:a multi-center,randomized,double-blind,bromocriptine-control trial

Objective To investigate the efficacy and safety of pramipexole in the treatment of Parkinson's disease. Methods A total of 208 Parkinson's patients with wearing off participated in a multi-center, 12-week randomized, bromocriptine-controlled, double blind, doubledummy and parallel-group trial. The efficacy of pramipexole was assessed according to the patient's diary card and using the Unified Parkinson's Disease Rating     

Is discharge to home after emergency department cardioversion safe for the treatment of recent-onset atrial fibrillation?

Recent-onset atrial fibrillation, defined as a first detected or recurrent episode of atrial fibrillation lasting less than 48 hours, is a commonly encountered dysrhythmia in the emergency department (ED). Cardioversion of stable patients in the ED with recent-onset atrial fibrillation without antecedent anticoagulation would allow for these patients to be discharged directly to home. We searched the literature to determine whether any studies have investigated the safety of this management strategy and identified five that addressed this question. These studies are reviewed herein; importantly, not one ED patient who was cardioverted in any of the five studies suffered a thromboembolic event - the feared complication responsible for most of the controversy surrounding the ED management of atrial fibrillation. According to the available evidence, we conclude that it would be within the standard of care to discharge home stable patients with recent-onset atrial fibrillation after cardioversion in the ED with adequate follow-up. It should be noted that although this strategy is safe and effective, the return visit rate for relapsed atrial fibrillation is 3% to 17%, and patients should be made aware of this possibility.     

Dietary treatment of hypercholesterolemia: do dietitians do it better? A randomized, controlled trial

PURPOSE: Current guidelines of the National Cholesterol Education Program (NCEP) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic. We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians. SUBJECTS AND METHODS: Hypercholesterolemic patients detected during a cholesterol screening project were randomly assigned to receive dietary counseling by a physician only (70 patients) or by a physician and a registered dietitian (66 patients). Patients were observed for 1 year to determine compliance with NCEP guidelines. RESULTS: At 3 months, the mean (+/- SD) decrease in the serum low-density lipoprotein (LDL) cholesterol level was 7% +/- 11% in the physician group and 12% +/- 10% in the dietitian group (P <0.004). A decrease of 10% or more in the LDL cholesterol level was seen in 25 patients (36%) in the physician group and 43 patients (65%) in the dietitian group (P <0.001). Only 40 (29%) of the patients in both groups achieved their NCEP target goals at 3 months. The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months, both groups lost about half of the beneficial effects on LDL cholesterol levels, and the difference between the two groups diminished. CONCLUSIONS: The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians. However, long-term compliance remains inadequate. For patients at high risk, consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications.     

Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial

Abstract

This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150^Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients’ own assessments of dry mouth and dry eyes, the investigators’ assessment of oral sicca symptoms, and the investigators’ overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.     

Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial

This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150^Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients’ own assessments of dry mouth and dry eyes, the investigators’ assessment of oral sicca symptoms, and the investigators’ overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.     

Is home blood pressure variability itself an interventional target beyond lowering mean home blood pressure during anti-hypertensive treatment?

It is unknown whether home blood pressure (BP) variability reduction is associated with target organ damage (TOD) protection independently of home mean BP reduction. We enrolled 310 hypertensive patients whose systolic BP (SBP) at home was over 135?mm?Hg. The subjects measured their BP in the morning and evening for 7 days. In addition, we measured urinary albumin excretion (UAE) as a marker of TOD before and after 6 months of candesartan treatment (+thiazidediuretics). At baseline, UAE was associated with average home SBP (r=0.24, P<0.001), the s.d. of home SBP (r=0.15, P=0.011), and the maximum home SBP (r=0.27, P<0.001). During the intervention, significant reductions were found in average home SBP (146±13 vs. 132±12?mm?Hg, P<0.001), s.d. of home SBP (12.9±4.8 vs. 11.8±4.4?mm?Hg, P<0.001), and maximum home SBP (172.5±18.0 vs. 155.9±17.5?mm?Hg, P<0.001). UAE levels were significantly reduced after 6 months of therapy compared with baseline (18.9 vs. 12.1?mg?g(-1) Cre, P<0.001). In multiple regression analysis, the treatment-induced reduction in UAE was significantly associated with that of average home BP (P=0.003) but was not associated with that of s.d. of home SBP or that of maximum home SBP. Home BP variability is not itself an interventional target beyond lowering mean home BP during anti-hypertensive treatment.     

Oral immune regulation using colitis extracted proteins for treatment of Crohn''''s disease: Results of a phase Ⅰ clinical trial

AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins (CEP) in Crohn's disease (CD) subjects. METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels. RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9 vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CD8+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period. CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation.     

Effect of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylorh A randomized, controlled trial

AIM: To study the effects of drug treatment on hyper-plastic gastric polyps infected with Helicobacter pylori (H pylori). METHODS: Forty-eight patients with hyperplastic gastric polyps (3-10 mm in diameter) infected with Hpylori were randomly assigned to a treatment group (n = 24) which received proton-pump inhibitor (omeprazole or lansopra-zole), clarithromycin, bismuth citrate and tinidazole, and a control group (n = 24) which received protective agent of gastric mucosa (tepretone) . Patients underwent endoscopy and H pylori examination regularly before enrollment and 1-12 mo after treatment. RESULTS: Twenty-two patients in the treatment group and 21 in the control group completed the entire test protocol. In the treatment group, polyps disappeared 1-12 mo (average, 6.5±1.1 mo) after the treatment in 15 of 22 patients (68.2%) and H pylori infection was eradicated in 19 of the 22 patients (86.4%). However, 12 months after the study, no change in polyps or H pylori status was seen in any controls (bP < 0.01). CONCLUSION: Most hyperplastic gastric polyps disappear after eradication of Hpylori.