Acetylsalicylsäure-Nonresponder nach ischämischem Insult bei geriatrischen Patienten

Background

The cardiovascular and cerebral ischemic risk is defined as the risk of suffering a thromboembolic event. The common secondary prophylaxis is still the use of acetylsalicylic acid (ASA). The usual daily dose is 100 mg. Efficacy concerning platelet aggregation is not routinely checked.

Material and methods

In this study, patients taking 100 mg aspirin daily (orally) were examined after admittance to the stroke unit due to a stroke or stroke recurrence. Platelet aggregation was performed using a Platelet Function Analyser (PFA 100).

Results

A total of 71 patients were examined, 53(73?%) had experienced a primary ischemic insult, and 18(25.4?%) stroke recurrence. Patients with prolonged closure time in the collagen/epinephrine cell (normal range 85–165 s) were classified as responders to ASA, while 14 (19.7?%) were classified as non-responders.

Conclusion

It remains open whether the secondary prophylaxis or a more effective inhibition of platelet aggregation results in the improved protection against a future event.     

Aspirin Dose Increase from 75 to 150 mg Suppresses Red Blood Cell Contribution to Suboptimal Platelet Response to Aspirin in Patients with CAD

Purpose

To verify the hypothesis that erythrocytes play a role in suboptimal blood platelet response to acetylsalicylic acid (ASA, aspirin) in subjects with coronary artery disease (CAD).

Methods

In a cross-over randomized controlled intervention study we evaluated blood platelet response to 30-day treatment with 75 mg/d or 150 mg/d of ASA (enteric coated) in CAD patients (n?=?125). In vitro platelet response to collagen or arachidonic acid was monitored with impedance aggregometry and plasma thromboxane B₂ was assayed immunoenzymatically. Blood morphology and several plasma biochemical parameters were determined using routine diagnostic procedures.

Results

CAD patients demonstrated lower blood platelet responsiveness to 75 mg/d of ASA compared to healthy subjects. The improved platelet responsiveness to 150 mg/d of ASA was particularly evident in “poor” responding patients. Positive correlations between platelet “poor” response to lower (75 mg/d) ASA dose and red blood cell count (R_s?=?0.215; p?<?0.04), haemoglobin (R_s?=?0.232; p?<?0.02) and haematocrit (R_s?=?0.239; p?<?0.02) were found in CAD patients. Association between “poor” platelet response with lower ASA dose was confirmed by conditional maximum likelihood logistic regression, which showed the independency between erythrocyte-derived parameters, as the risk factors for suboptimal platelet response to ASA, and other risk factors, like CRP or LDL-cholesterol. In “poor” ASA responders taking the higher ASA dose (150 mg/d) the correlation between platelets’ response to ASA and erythrocyte-derived parameters was not significant.

Conclusions

Red blood cell parameters are associated with suboptimal blood platelet response to ASA in patients with CAD. Such a platelet refractoriness to ASA may be effectively overcome by increasing the ASA dose.     

Dipyridamole with Low-Dose Aspirin Augments the Infarct Size-Limiting Effects of Simvastatin

Purpose

Statins protect against ischemia-reperfusion injury and limit myocardial infarct size (IS). This effect is dependent on increased generation of adenosine by ecto-5′ nucleotidase and downstream activation of cyclooxygenase-2 (COX2). Dipyridamole (DIP) augments the IS-limiting effects of statins by blocking the cellular reuptake of adenosine; whereas aspirin (ASA) attenuates the effect by inhibiting COX2. We studied the effect of acute administration of DIP, ASA and their combination on the IS-limiting effect of simvastatin (SIM).

Methods

Rats received oral SIM (10 mg/kg/d) or vehicle for 3 days. Rats underwent 30 min of coronary artery occlusion and 4 h reperfusion. After 5 min of ischemia rats received i.v. DIP (5 mg/kg), ASA (20 mg/kg or 2 mg/kg) or DIP+ASA (2 mg/kg) or vehicle alone. Ischemia area at risk (AR) was assessed by blue dye and IS by TTC. Myocardial samples were analyzed for the activation of Akt, ERK 1/2, endothelial nitric oxide synthase (eNOS), and cyclic-AMP-response-element-binding-protein (CREB).

Results

SIM limited IS. High- or low-dose ASA alone had no effect on IS. DIP alone or with low-dose ASA significantly reduced IS. Low-dose ASA did not attenuate the SIM effect, whereas high-dose ASA completely blocked the effect. The combination of DIP+low-dose ASA+SIM resulted in the smallest IS. Both SIM and DIP+low-dose ASA augmented Akt phosphorylation and their effect was additive. Both SIM and DIP+low-dose ASA augmented eNOS, ERK 1/2 and CREB phosphorylation.

Conclusions

During acute myocardial ischemia, DIP alone or with low-dose ASA limits IS and does not attenuate the IS-limiting effect of SIM as high-dose ASA.     

The Role of Food for the Formation and Prevention of Gastrointestinal Lesions Induced by Aspirin in Cats

Background/Aims

The effects of feeding conditions (fasted or fed) and dietary fiber (DF) in the diet on gastrointestinal (GI) damage induced by aspirin (ASA) were examined in cats.

Methods

Plain ASA (P-ASA, 20 mg/kg) or one enteric-coated ASA tablet (EC-ASA, containing 100 mg ASA) was administered p.o. once daily for 3 or 7 days just after morning meal, 3 h after the evening meal, or in the morning without a morning meal (fasted). Several types of diet, dry food (DRY, DF: 2.8 %), canned food (CAN, DF: 0.4 %), and diets with added cellulose or pectin were provided twice daily.

Results

P-ASA or EC-ASA administered just after feeding of DRY caused marked lesions in the GI tract, although EC-ASA did not produce any lesions in the stomach. GI damage was markedly decreased when ASA was administered 3 h after the evening meal. The induction of lesions by EC-ASA was markedly decreased in cats that ate CAN, but lesions were induced in cats fed CAN with added cellulose (6 %). The addition of pectin (6 %) to the DRY markedly decreased the induction of lesions by EC-ASA.

Conclusions

The results indicate that the induction of GI lesions by ASA was highly dependent on the feeding conditions and DF. To minimize the induction of GI damage, it would be better to take ASA 3 h after the evening meal, or after consuming diets that contain low amounts of insoluble DF and high amounts of soluble DF.     

Risk factor profiles,drug usage,and prevalence of aspirin-associated gastroduodenal injuries among high-risk cardiovascular Japanese patients: the results from the MAGIC study

Background

Low-dose aspirin is widely used for the prevention of cardiovascular events. The prevalence of gastroduodenal injuries and the risk factor profile including gastroprotective drug therapy needs to be clarified in Japanese patients taking daily aspirin for cardioprotection.

Methods

This Management of Aspirin-induced Gastro-Intestinal Complications (MAGIC) study was conducted with a prospective nationwide, multicenter, real-world registry of Japanese patients at high-risk of cardiovascular diseases who were taking regular aspirin (75–325 mg) for 1 month or more. All patients underwent endoscopic examination for detection of gastroduodenal ulcer and mucosal erosion. The risk factor profiles including the concurrent drug therapy were compared for those patients with gastroduodenal problems and those without.

Results

Gastroduodenal ulcer and erosion were detected in 6.5, and 29.2 % of the 1,454 patients receiving aspirin, respectively. H. pylori infection was associated with an increased risk for ulcer: OR 1.83 (1.18–2.88 p = 0.0082). Risk of erosion was lower with enteric-coated aspirin than with buffered aspirin: odds ratio (OR) 0.47 (0.32–0.70, p = 0.0002). Patients receiving proton pump inhibitors had lower risks for both gastroduodenal ulcer and erosion: OR 0.34 (0.15–0.68, p = 0.0050) and 0.32 (0.22–0.46, p < 0.0001), respectively. However, those receiving histamine 2-receptor antagonists had reduced risks for erosion but not for ulcer: OR 0.49 (0.36–0.68, p < 0.0001).

Conclusion

Gastroduodenal ulcer and erosion are common in Japanese patients taking low dose aspirin for cardioprotection. Proton pump inhibitors reduce the risk of gastroduodenal mucosal injury.     

Bacteriological analysis of bile in acute cholecystitis according to the Tokyo guidelines

Background

We performed bacteriological analysis of bile in acute cholecystitis (AC) patients graded in severity according to the Tokyo guidelines.

Methods

We enrolled 163 AC patients in whom bacteriological analysis of bile was performed.

Results

Significant differences in age (60 vs. 67 years), body temperature (BT) (37.2 vs. 37.6°C), white blood cell count (13,033 vs. 15,177/mm³), and serum C-reactive protein (CRP) (8.9 vs. 16.9 mg/dL) were found between the Mild and Moderate severity groups. The prevalence of bactibilia differed significantly between Mild and Moderate patients (45.3 vs. 67.0%, P = 0.0107); however, there were no significant differences in the bacterial strains, prevalence of antimicrobial resistance, or polymicrobial isolation frequency between the 2 groups. Our local antibiogram revealed that several microorganisms showed higher resistance rates; these were also isolated even in Mild cases. Advanced age, high BT, high serum CRP, and presence of marked local infection were identified as being significantly associated with high risk of bactibilia. Receiver operating characteristic curve analysis indicated the optimal cutoff value of age to be 65 years, of BT to be 37.5°C, and of serum CRP to be 13.4 mg/dL.

Conclusion

Adequate broad-spectrum antimicrobial therapy should be administered perioperatively even for Mild patients classified according to the current Tokyo guidelines. These results suggest that more precise severity grades may need to be established, including age and CRP as additional parameters.     

Efficacy and safety of sequential therapy versus standard triple therapy in Helicobacter pylori eradication in Kashmir India: a randomized comparative trial

Background

Increasing resistance against Helicobacter pylori has resulted in reduced eradication rates.

Objective

This study aims to determine whether eradication rates for H. pylori infection with sequential therapy is better than standard triple therapy.

Patients

Patients with endoscopy documented peptic ulcer and H. pylori infection confirmed by histology and rapid urease test.

Intervention

Patients were randomized into two groups; 134 received standard triple therapy (pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1 g each administered twice daily) for 10 days and 138 received sequential regimen (pantoprazole 40 mg plus amoxicillin 1 g twice daily for 5 days followed by 40 mg pantoprazole, 500 mg clarithromycin, and 500 mg tinidazole each administered twice daily for 5 days). Eradication was confirmed by histology and rapid urease test. Compliance and adverse effects were determined by the recovery of empty medicine strips and questioning.

Results

The eradication rates with sequential therapy were significantly greater than with standard therapy on both intention-to-treat analysis (76.0 % vs. 61.9 %, p?=?0.005; difference, 14.1 % [95 % CI, 6.5–19 %] and per protocol analysis (84.6 % vs. 67.4 %, p?=?0.002; difference, 17.2 % [95 % CI, 8.5–23.5 %]). The incidence of side effects did not differ between the two therapy groups. One patient in standard therapy discontinued treatment due to side effects.

Limitation

Cultures were not performed. Loss to follow up was 5.2 % in standard therapy and 6.5 % in sequential therapy.

Conclusion

Sequential therapy was significantly more effective than standard therapy for eradicating H. pylori infection in peptic ulcer disease in Asian patients. Side effects were similar.     

Evaluation of long-term entecavir treatment in stable chronic hepatitis B patients switched from lamivudine therapy

Purpose

Current Japanese guidelines recommend that patients should be switched from lamivudine to entecavir when they meet certain criteria. This analysis examines the efficacy and safety of long-term entecavir therapy in patients who were switched to entecavir after 24 weeks’ lamivudine therapy in Japanese studies ETV-047 and ETV-060.

Methods

The Phase II Japanese study ETV-047 assessed the efficacy of different entecavir doses when compared with lamivudine. A total of 33 Japanese patients who received lamivudine 100 mg daily in ETV-047 entered the open-label rollover study ETV-060 and subsequently received treatment with entecavir 0.5 mg daily. Hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, and resistance were evaluated among patients with available samples for up to 96 weeks. Safety was assessed throughout the treatment period.

Results

After 96 weeks of entecavir therapy in ETV-060, 90% of patients achieved HBV DNA <400 copies/mL as compared to 21% of patients who completed 24 weeks of lamivudine therapy in ETV-047. Increasing proportions of patients achieved ALT normalization and HBeAg seroconversion following long-term entecavir treatment. No patients experienced virologic breakthrough, and substitutions associated with entecavir resistance were not observed in patients with detectable HBV DNA. Entecavir was well tolerated during long-term treatment.

Conclusions

Switching lamivudine-treated patients with chronic hepatitis B to entecavir results in increased virologic suppression with no evidence of resistance through 2 years of entecavir therapy. These findings support recommendations in the current Japanese treatment guidelines that stable lamivudine patients should be switched to entecavir.     

Relationship Between Endothelial Functions and Acetylsalicylic Acid Resistance in Newly Diagnosed Hypertensive Patients

Background:

We aimed to investigate the effects and dose dependency of aspirin on endothelial functions and prevalence of aspirin resistance in newly diagnosed hypertensive patients without previous drug therapy and development of cardiac complications.

Hypothesis:

Acetylsalicyclic acid improves endothelial function.

Methods:

Fifty‐eight hypertensive patients and 61 healthy subjects in the control group were included in the study. Endothelial functions of the patient and control groups were evaluated with brachial artery examination. Patient and control groups were divided into 2 groups. A total of 100 mg and 300 mg of aspirin were given to the separate groups for 1 week. After 1 week, endothelial functions were reevaluated and aspirin resistance examined with a platelet function analyzer (PFA‐100; Dade Behring, Marbourg, Germany).

Results:

Baseline flow‐mediated dilatation (FMD) change percent in hypertensive patients was 9.8%, and it was significantly lower than in the control group (12%) (P < 0.001). Frequency of acetylsalicylic acid (ASA) resistance was 20% and 26% in control and hypertensive patient groups, respectively (P = not significant). ASA resistance was 28% and 24% in 100 mg and 300 mg in hypertensive patients, respectively (P = not significant). FMD change percent increased both in the control and hypertensive groups after ASA treatment from 12.4% to 13.3% and 9.8 % to 11.9 %, respectively. FMD percentage change was significantly increased in hypertensive patients irrespective of ASA resistance (P = 0.02, for ASA resistance [+]; P < 0.012, for ASA resistance [?]).

Conclusions:

Endothelial functions were impaired more in hypertensive patients compared to the control group. Endothelial functions were improved with all ASA doses in hypertensive patients irrespective of ASA resistance. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

C-reactive protein as a marker of complicated diverticulitis in patients on anti-inflammatory medications

Background

Diverticulitis is a common indication for surgical emergency room admission, often leading to abdominal computed tomography (CT) scanning for both diagnosis and staging. C-reactive protein (CRP) has been identified as a useful biomarker of inflammation. Aspirin and corticosteroids are known to down-regulate CRP production. In this study, we evaluated the usefulness of CRP as a biomarker for complicated diverticulitis and specifically in patients on anti-inflammatory medications: aspirin and corticosteroids.

Methods

We analyzed the medical records of patients diagnosed at one medical center during a two-year period, with left-sided diverticulitis, according to clinical data and CT scan. Disease severity was assessed by the Hinchey score using the radiological findings detected by CT.

Results

A total of 295 patients were included in the study. Two hundred and forty-three (82 %) were classified with uncomplicated (Hinchey 1a) and 52 (18 %) with complicated disease (Hinchey > 1a). Mean CRP levels were 133.5 and 63.5 mg/ml for those with complicated and uncomplicated disease, respectively (p < 0.001), and 139 and 60 mg/ml, respectively (p < 0.001) in the subgroup of patients taking aspirin (n = 61). For 14 patients on corticosteroid treatment, the difference in mean CRP levels for complicated and uncomplicated disease was not statistically significant. CRP > 90 mg/ml had 88 % sensitivity and 75 % specificity for complicated disease.

Conclusions

The CRP level distinguished between complicated and uncomplicated disease among left-sided diverticulitis patients including those taking aspirin, but not among those on corticosteroid treatment.     

The Impact of Financial Barriers on Access to Care, Quality of Care and Vascular Morbidity Among Patients with Diabetes and Coronary Heart Disease

BACKGROUND

The prevalence and consequences of financial barriers to health care among patients with multiple chronic diseases are poorly understood.

OBJECTIVE

We sought to assess the prevalence of self-reported financial barriers to health care among individuals with diabetes and coronary heart disease (CHD) and to determine their association with access to care, quality of care and clinical outcomes.

DESIGN

The 2007 Centers for Disease Control Behavioral Risk Factor Surveillance Survey.

PARTICIPANTS

Diabetic patients with CHD.

MAIN MEASURES

Financial barriers to health care were defined by a self-reported time in the past 12 months when the respondent needed to see a doctor but could not because of cost. The primary clinical outcome was vascular morbidity—a composite of stroke, retinopathy, nonhealing foot sores or bilateral foot amputations.

KEY RESULTS

Among the 11,274 diabetics with CHD, 1,541 (13.7 %) reported financial barriers to health care. Compared to individuals without financial barriers, those with financial barriers had significantly reduced rates of medical assessments within the past 2 years, hemoglobin (Hgb) A1C measurements in the past year, cholesterol measurements at any time, eye and foot examinations within the past year, diabetic education, antihypertensive treatment, aspirin use and a higher prevalence of vascular morbidity. In multivariable analyses, financial barriers to health care were independently associated with reduced odds of medical checkups (Odds Ratio [OR], 0.61; 95 % Confidence Intervals [CI], 0.55–0.67), Hgb A1C measurement (OR, 0.85; 95 % CI, 0.77–0.94), cholesterol measurement (OR, 0.76; 95 % CI, 0.67–0.86), eye (OR, 0.85; 95 % CI, 0.79–0.92) and foot (OR, 0.92; 95 % CI, 0.84–1.00) examinations, diabetic education (OR, 0.93; 95 % CI, 0.87–0.99), aspirin use (OR, 0.88; 95 % CI, 0.81–0.96) and increased odds of vascular morbidity (OR, 1.23; 95 % CI, 1.14–1.33).

CONCLUSIONS

In diabetic adults with CHD, financial barriers to health care were associated with impaired access to medical care, inferior quality of care and greater vascular morbidity. Eliminating financial barriers and adherence to guideline-based recommendations may improve the health of individuals with multiple chronic diseases.     

Safety and Effectiveness of Low-Dose Propofol Sedation During and After Esophagogastroduodenoscopy in Child A and B Cirrhotic Patients

Background

Effective and safe sedation for patients with liver cirrhosis is problematic.

Aim

To examine the safety and effectiveness of low-dose propofol sedation during and after esophagogastroduodenoscopy (EGD) in cirrhotic patients.

Methods

Study 1 was a prospective study in cirrhotic patients who underwent diagnostic EGD under propofol sedation. Propofol was given by bolus injection with an age-adjusted standard protocol consisting of 40 mg for patients <70 years, 30 mg for patients aged 70–89 years; additional injections of 20 mg propofol were given up to a maximum of 120 mg. The principal parameter was the occurrence of adverse events within 24 h after EGD. Secondary parameters included successful procedures, complications, and full recovery within 60 min. In Study 2, the residual effects of propofol were evaluated using a driving simulator and blood propofol concentrations in a subset of cirrhotic patients undergoing EGD and compared with healthy individuals. The principal parameter was driving ability.

Results

Study 1: Consecutive cirrhotic patients were entered and all 163 successfully completed EGD. The mean dose of propofol was 46 mg (range 30–120 mg). No complications occurred. Full recovery had occurred in 100 % 60 min after the procedure. No adverse events occurred within 24 h after EGD. Study 2: There were no significant differences in blood propofol levels between cirrhotic patients (n = 21) and healthy individuals (n = 20) after sedation. In cirrhotic patients, there was no deterioration in driving ability as compared with healthy individuals.

Conclusion

Low-dose propofol sedation provided safe and effective sedation for EGD in cirrhotic patients with rapid recovery.     

Abnormal PFA-100 closure time is associated with increased platelet aggregation in patients presenting with chest pain

Background

Antiplatelet therapy has been proven to be effective for both primary and secondary prevention of myocardial infarction, stroke, and cardiovascular death. However, a significant proportion of patients treated with aspirin experience ischemic events. A number of prospective studies have demonstrated that decreased responsiveness to antiplatelet therapy as measured by various methods, is strongly associated with an increase in clinical events. Our objective was to characterize platelet function in patients presenting with chest pain using a point-of-care assay, PFA-100^® and correlating results to traditional platelet aggregometry to determine if patients with aspirin non-responsiveness have increased clinical sequelae.

Methods

Platelet function was assessed using PFA-100^®, flow cytometry, and optical aggregometry in 94 patients presenting to the emergency department with chest pain. All patients were on aspirin 81–325 mg daily. Clinical events occurring during the index hospitalization were documented.

Results

Forty-seven patients (50%) were defined as aspirin non-responders by PFA-100^® (collagen-epinephrine closure time ≤ 193). Compared to aspirin responders, aspirin non-responders had higher levels of mean platelet aggregation to adenosine diphosphate (ADP) (P = 0.004) and high dose epinephrine (P = 0.03). Furthermore, expression of PAC-1 was significantly increased in patients with aspirin nonresponse as compared to aspirin responders (P = 0.003 and P = 0.0006 respectively). No significant difference in clinical events during the index hospitalization was noted between aspirin non-responders and aspirin responders.

Conclusion

Patients presenting with chest pain who have abnormal PFA-100 closure times have increased platelet aggregation and activation however this aspirin non-responsiveness does not correlate with increased clinical events in the index hospitalization.

     

Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon

Purpose

Clinical and experimental investigations demonstrated that metformin, a widely used anti-diabetic drug, exhibits cardioprotective properties against myocardial infarction. Interestingly, metformin was previously shown to increase the expression of PGC-1α a key controller of energy metabolism in skeletal muscle, which is down-regulated in diabetic conditions. We hypothesized that chronic treatment with metformin could protect the aged, diabetic heart against ischemia-reperfusion injury (IRI) by up-regulating PGC-1α and improving the impaired functionality of diabetic mitochondria.

Methods

Following 4 weeks of metformin (300 mg/kg) administered in the drinking water, 12 month-old diabetic Goto Kakizaki and non-diabetic Wistar rat hearts were assigned for infarct measurement following 35 min ischemia and 60 min reperfusion or for electron microscopy (EM) and Western blotting (WB) investigations.

Results

Metformin elicited a cardioprotective effect in both non-diabetic and diabetic hearts. In contrast with the diabetic non-treated hearts, the diabetic hearts treated with metformin showed more organized and elongated mitochondria and demonstrated a significant increase in phosphorylated AMPK and in PGC-1α expression.

Conclusions

In summary these results show for the first time that chronic metformin treatment augments myocardial resistance to ischemia-reperfusion injury, by an alternative mechanism in addition to the lowering of blood glucose. This consisted of a positive effect on mitochondrial structure possibly via a pathway involving AMPK activation and PGC-1α. Thus, metformin prescribed chronically to patients may lead to a basal state of cardioprotection thereby potentially limiting the occurrence of myocardial damage by cardiovascular events.     

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Purpose

Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudine-refractory Japanese patients treated with entecavir for 3 years.

Methods

Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples.

Results

After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55% (36/65) of patients had hepatitis B virus (HBV) DNA of >400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of ≥1 × upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion. A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of >400 copies/mL, 84% (27/32) had ALT of ≥1 × ULN, and 15% (4/27) achieved HBe seroconversion. Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares.

Conclusions

Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.     

Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus

Aims/hypothesis

Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus. There is emerging evidence that GLP-1 has anti-inflammatory activity in humans, with murine studies suggesting an effect on macrophage polarisation. We hypothesised that GLP-1 analogue therapy in individuals with type 2 diabetes mellitus would affect the inflammatory macrophage molecule soluble CD163 (sCD163) and adipocytokine profile.

Methods

We studied ten obese type 2 diabetes mellitus patients starting GLP-1 analogue therapy at a hospital-based diabetes service. We investigated levels of sCD163, TNF-α, IL-1β, IL-6, adiponectin and leptin by ELISA, before and after 8 weeks of GLP-1 analogue therapy.

Results

GLP-1 analogue therapy reduced levels of the inflammatory macrophage activation molecule sCD163 (220 ng/ml vs 171 ng/ml, p?<?0.001). This occurred independent of changes in body weight, fructosamine and HbA_1c. GLP-1 analogue therapy was associated with a decrease in levels of the inflammatory cytokines TNF-α (264 vs 149 pg/ml, p?<?0.05), IL-1β (2,919 vs 748 pg/ml, p?<?0.05) and IL-6 (1,379 vs 461 pg/ml p?<?0.05) and an increase in levels of the anti-inflammatory adipokine adiponectin (4,480 vs 6,290 pg/ml, p?<?0.002).

Conclusions/interpretation

In individuals with type 2 diabetes mellitus, GLP-1 analogue therapy reduces the frequency of inflammatory macrophages. This effect is not dependent on the glycaemic or body weight effects of GLP-1.     

Safety and efficacy of 1-week levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori-related peptic ulcer disease in Kashmir, India

Background and Objectives

There is no ideal therapy for eradication of Helicobacter pylori infection. We evaluated the efficacy and safety of 1-week triple therapy with rabeprazole, levofloxacin, and tinidazole in a metronidazole resistance prevalent region for eradicating H. pylori infection in patients with gastroduodenal ulcers.

Methods

This was an open-label, prospective study. Consecutive patients with endoscopy-proven duodenal or gastric ulcer and who were H. pylori-positive were treated with levofloxacin 500 mg once a day, rabeprazole 20 mg twice a day, and tinidazole 500 mg twice daily for 7 days followed by rabeprazole 20 mg OD for 8 weeks. Endoscopy was repeated 8 weeks after the end of therapy to check for ulcer healing and H. pylori status.

Results

One hundred and thirty-one patients with gastroduodenal ulcers (duodenal 118, and gastric 13) were included. Drug compliance was 97.7 %. The eradication rate of H. pylori by intention-to-treat analysis was 85.5 % (95 % confidence interval 79.5–91.5) (112 of 131 patients) and by per-protocol analysis was 91.8 % (95 % confidence interval 86.9–96.7) (112 of 122 patients). Adverse effects were reported in 17 %: abdominal pain in 3.05 %, metallic taste in 6.87 %, and nausea and vomiting in 4.58 %.

Conclusions

Levofloxacin–tinidazole-based triple therapy was highly effective and safe as a first-line regimen in Indian patients with gastroduodenal ulcer disease associated with H. pylori infection. The regimen was well tolerated.     

Effect of Including Cancer Mortality on the Cost-Effectiveness of Aspirin for Primary Prevention in Men

BACKGROUND

Recent data suggest that aspirin may be effective for reducing cancer mortality.

OBJECTIVE

To examine whether including a cancer mortality-reducing effect influences which men would benefit from aspirin for primary prevention.

DESIGN

We modified our existing Markov model that examines the effects of aspirin among middle-aged men with no previous history of cardiovascular disease or diabetes. For our base case scenario of 45-year-old men, we examined costs and life-years for men taking aspirin for 10 years compared with men who were not taking aspirin over those 10 years; after 10 years, we equalized treatment and followed the cohort until death. We compared our results depending on whether or not we included a 22 % relative reduction in cancer mortality, based on a recent meta-analysis. We discounted costs and benefits at 3 % and employed a third party payer perspective.

MAIN MEASURE

Cost per quality-adjusted life year (QALY) gained.

KEY RESULTS

When no effect on cancer mortality was included, aspirin had a cost per QALY gained of $22,492 at 5 % 10-year coronary heart disease (CHD) risk; at 2.5 % risk or below, no treatment was favored. When we included a reduction in cancer mortality, aspirin became cost-effective for men at 2.5 % risk as well (cost per QALY, $43,342). Results were somewhat sensitive to utility of taking aspirin daily; risk of death after myocardial infarction; and effects of aspirin on stroke, myocardial infarction, and sudden death. However, aspirin remained cost-saving or cost-effective (< $50,000 per QALY) in probabilistic analyses (59 % with no cancer effect included; 96 % with cancer effect) for men at 5 % risk.

CONCLUSIONS

Including an effect of aspirin on cancer mortality influences the threshold for prescribing aspirin for primary prevention in men. If such an effect is real, many middle-aged men at low cardiovascular risk would become candidates for regular aspirin use.     

A randomized,open-label study comparing low-dose clevudine plus adefovir combination therapy with clevudine monotherapy in naïve chronic hepatitis B patients

Purpose

Clevudine 30 mg showed potent antiviral activity with a marked post-treatment antiviral effect. However, long-term treatment with clevudine monotherapy induced resistance and myopathy in some cases. The objective of this study is to evaluate the preliminary efficacy and safety of the combination of clevudine 20 mg and adefovir compared to clevudine monotherapy.

Methods

Seventy-four patients were randomized to either a combination of clevudine 20 mg and adefovir or clevudine 20 or 30 mg and were treated for 2 years. The viral kinetics for 24 weeks, virological response [VR; hepatitis B virus (HBV) DNA less than 300 copies/ml], and the biochemical response [BR; normal alanine aminotransferase (ALT)] were assessed.

Results

There was no difference in baseline characteristics among the three groups. Viral kinetics study showed no statistically significant difference among them during 24 weeks. The combination group showed 95 % virological response with a statistically significant difference compared to the clevudine 30 mg (67 %) and 20 mg (71 %) groups (p = 0.0376). Biochemical response rates were similar in all groups (78–94 %). No resistance was reported in the combination group, while 20 % of patients treated with clevudine 30 mg or 20 mg reported resistance during 2 years. Muscle-related symptoms such as myalgia (1 in clevudine 30 mg, 1 in the combination group) and muscle weakness (1 in clevudine 30 mg, 2 in clevudine 20 mg) were reported in five patients (7 %); of these, three patients discontinued the study.

Conclusion

We concluded that the combination of clevudine 20 mg and adefovir produced a potent antiviral response together with a good resistance profile compared to clevudine monotherapy at 96 weeks in this pilot study.     

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: A randomized study

Background

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India.

Methods

A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily).

Results

The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4 % (95 % CI 85.8–96.1 %) vs. 81.8 % (95 % CI 73.9–87.8 %) (p?=?0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2 % (95 % CI 80.9–93.0 %) vs. 79.1 % (95 % CI 71.1–85.4 %), p?=?0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6 % in the triple therapy group vs. 23.5 % in sequential group, p?=?0.12). Follow up was incomplete in 3.3 % and 4.7 % patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy.

Conclusions

Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.