Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.

Quality of life, continence and frequency of pouchitis following laparoscopic versus open colectomy and ileal pouch-anal anastomosis: an Irish perspective.

BACKGROUND: This study aims to assess quality of life outcomes, continence, rates of pouchitis and predictors of pouchitis for patients undergoing laparoscopic versus open three-stage ileal pouch-anal anastomosis (IPAA) surgery in our institution. METHODS: Forty-two patients having had three-stage (IPAA) surgery were identified. One was excluded as they had undergone pouchectomy. A postal questionnaire followed by telephone contact was undertaken. The questionnaire was based on The Gastrointestinal Quality of Life Index (GIQLI) and Wexner/Cleveland Clinic Faecal Incontinence Symptom Severity Scoring Systems. AIMS: Our aim was to assess morbidity, quality of life, incidence of pouchitis and continence following restorative panproctocolectomy and IPAA. RESULTS: Thirty-five patients completed the response. The median age at colectomy of our patient population was 32 years. 57 % were male and 43 % were female. 54.3 % of cases were carried out laparoscopically. 8/19 patients who had laparoscopic surgery had pouchitis (42.1 %) versus 9/16 patients who had open surgery (56.3 %). The median Wexner score was 0. Nine patients (25.7 %) had a GIQLI score that was within or above the range reported for healthy controls. The rate of complications was 31.7 % for emergency cases and 25.7 % for elective cases. The rate of pouchitis in this group was 48.5 %. Overall pelvic sepsis rate was 12.8 %. CONCLUSIONS: Ileal pouch-anal anastomosis is a successful and well-tolerated procedure with 94 % of patients opting to have the surgery again. Preliminary results do not show any significant difference in the incidence of pouchitis following laparoscopic surgery.

The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

A New Individually Addressable Micro-LED Array for Photogenetic Neural Stimulation.

Here, we demonstrate the use of a micro light emitting diode (LED) array as a powerful tool for complex spatiotemporal control of photosensitized neurons. The array can generate arbitrary, 2-D, excitation patterns with millisecond and micrometer resolution. In particular, we describe an active matrix control address system to allow simultaneous control of 256 individual micro LEDs. We present the system optically integrated into a microscope environment and patch clamp electrophysiology. The results show that the emitters have sufficient radiance at the required wavelength to stimulate neurons expressing channelrhodopsin-2 (ChR2).

The individual and combined influence of HIV and hepatitis C virus on dyslipidaemia in a high-risk Hispanic population.

OBJECTIVES: To assess the effects of chronic hepatitis C (HCV) and HIV infection on dyslipidaemia in a Hispanic population at high risk of insulin resistance. METHODS: We compared serum lipids and C-reactive protein (CRP) in 257 Hispanic adults including 47 HIV- mono-infected, 43 HCV-mono-infected and 59 HIV/HCV-co-infected individuals as well as 108 healthy controls. We also assessed the effect of HCV on lipid alterations associated with antiretroviral therapy (ART), and the impact of HCV and HIV on the associations among insulin resistance, triglycerides and cholesterol. RESULTS: HCV infection was associated with lower total and low-density lipoprotein (LDL) cholesterol, but not high-density lipoprotein (HDL) cholesterol or triglycerides compared with healthy controls. HIV infection was associated with higher triglycerides and lower HDL, but not total or LDL cholesterol. HCV mitigated the elevation of triglycerides associated with ART. In healthy Hispanic adults, insulin resistance was significantly correlated with higher triglycerides, CRP and lower HDL. HIV infection nullified the association of insulin resistance with triglycerides and HDL, and the association of triglycerides with LDL. HCV infection nullified the association of insulin resistance with triglycerides, HDL and CRP. CONCLUSIONS: HCV co-infection alters the profile of HIV-associated dyslipidaemia. The clinical significance of these findings for cardiovascular complications in HIV merits further study.

Evaluation of the BAX system for detection of Listeria monocytogenes in foods: collaborative study.

A multilaboratory study was conducted to compare the automated BAX system and the standard cultural methods for detection of Listeria monocytogenes in foods. Six food types (frankfurters, soft cheese, smoked salmon, raw, ground beef, fresh radishes, and frozen peas) were analyzed by each method. For each food type, 3 inoculation levels were tested: high (average of 2 CFU/g), low (average of 0.2 CFU/g) and uninoculated controls. A total of 25 laboratories representing government and industry participated. Of the 2335 samples analyzed, 1109 were positive by the BAX system and 1115 were positive by the standard method. A Chi square analysis of each of the 6 food types, at the 3 inoculation levels tested, was performed. For all foods, except radishes, the BAX system performed as well as or better than the standard reference methods based on the Chi square results.

The influence of bladder filling on anorectal function.

OBJECTIVE: The aim of this study was to develop a technique to simultaneously evaluate bladder and anorectal function. In particular, this study was designed to determine if anal sphincter resting pressure, anal sphincter squeeze pressure and rectal sensation change with bladder filling. PATIENT AND METHODS: A pilot study of ten female patients who presented to the pelvic physiology unit for assessment of urinary symptoms was performed. All patients completed a symptom questionnaire and quality of life assessment form. Following informed consent a baseline urodynamic test was performed with the bladder empty and subsequently followed by an anorectal manometric test. Changes in anal sphincter resting pressure, squeeze pressure and rectal pressure were recorded over a ten-minute period. With the patient lying in the left lateral position, the bladder was then filled with isotonic saline at room temperature at a constant rate of 30 ml/min. A continuous assessment of changes in anal sphincter resting pressure during bladder filling was made. Anal sphincter squeeze pressure and rectal sensation were measured at fixed intervals during bladder filling (50, 100, 150 ml etc.) and at fixed intervals relative to bladder capacity (25, 50, 75 and 100% capacity) by stopping bladder filling at the appropriate level. RESULTS: There was no significant change in anal sphincter resting pressure (Mean difference(s.d.) between bladder full and empty = 2.7(5.6) P = 0.92*), squeeze pressure (Mean(s.d.) difference = 9.5(26.3) P = 0.86*) and rectal sensation (Mean difference(s.d.) first sensation 10(15.2) P = 0.958; Mean difference(s.d.) urgency = 10(17.8) P = 0.07*) on bladder filling. CONCLUSION: Under normal physiological circumstances, bladder filling does not influence anorectal function. * STATISTICAL ANALYSIS: Wilcoxon signed rank sum test. P < 0.05 considered significant. Units = mmHg

Long-term infection rates associated with the pectoral versus abdominal approach to cardioverter- defibrillator implants.

Infection is an uncommon (0% to 6.7%) but serious complication after implantable cardioverter-defibrillator (ICD) implantation. All ICD primary implants, replacements, or revisions performed at the Massachusetts General Hospital between April 1983 and May 1999 were reviewed. A total of 21 ICD-related infections (1.2%) were identified among 1,700 procedures affecting 1.8% of the 1,170 patients who underwent a primary implant, a generator change, or a revision of their systems. The mean follow-up time was 35 +/- 33 months. Of the 959 patients with long-term follow-up, 19 of the 584 patients (3.2%) with abdominal and 2 of the 375 patients (0.5%) with pectoral systems developed ICD-related infections (p = 0.03). There was no significant difference between the infection rate among the 959 primary ICD implants and the 447 replacements or system revisions. Only 5 of the patients (24%) had systemic signs of infection, including fever (T>100.5) and elevated white blood count >12,000. Cultures from the wound revealed staphylococcal species in 16 patients (76%). Nineteen patients were treated with removal of the entire ICD system in addition to intravenous antibiotics for 2 to 4 weeks. A decrease in the incidence of ICD-related infection has occurred since the advent of transvenous pectoral systems. The main organism responsible for ICD infection is Staphylococcus. The mainstay of ICD infection management consists of complete removal of the entire implanted system.

Acute respiratory distress syndrome complicating Plasmodium vivax malaria.

Malaria is one of the most common infectious diseases in the world, and severe respiratory complications have been described mainly in association with Plasmodium falciparum. We describe a case of acute respiratory distress syndrome complicating infection with P. vivax in the setting of relatively low parasitemia in a 47-yr-old woman after a brief trip to Papua New Guinea. A review of the literature shows that pulmonary complications of P. vivax are rare but occur more frequently than generally acknowledged. Pathogenic mechanisms of these complications are discussed.

Long-term clinical outcome of patients with prior myocardial infarction after palliative radiofrequency catheter ablation for frequent ventricular tachycardia.

Patients with coronary artery disease and hemodynamically tolerated, highly frequent, sustained monomorphic ventricular tachycardia (VT) may undergo radiofrequency catheter ablation (RFCA) for elimination of > or = 1 morphologically distinct VTs. The purpose of this study was to evaluate the long-term clinical benefit following RFCA as a palliative treatment of highly frequent or incessant ischemic VT. Fifty-five patients underwent RFCA of 62 VTs. The target VT was successfully ablated in 82% of patients. Complication and perioperative mortality rates were 7.2% and 1.8%, respectively. At 5 years, total mortality was 51% and probability of freedom from all ventricular tachyarrhythmias was 28%. All patients had highly frequent or incessant drug-refractory VT before RFCA. Clinical benefit was defined as either freedom from all ventricular tachyarrhythmias, or a reduction in frequency of recurrence from > 1 episode per month before RFCA to < or = 1 episode per year of any ventricular tachyarrhythmia, including all appropriate implantable cardioverter defibrillator (ICD) therapies. By this definition, 54% of the patients continued to benefit from RFCA at 5 years. Of 19 variables analyzed with a Cox univariate model, only the presence of a left ventricular aneurysm and a previously implanted ICD were predictive of any ventricular arrhythmia recurrence. However, at 5 years over half of the surviving patients still continued to benefit from RFCA of their clinical VT. Because the overall rate of any ventricular tachyarrhythmia occurrence during follow-up is high, additional protection, such as an ICD, is required.

Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.

Highly active antiretroviral therapy has decreased human immunodeficiency virus (HIV)-associated mortality; other comorbidities, such as chronic liver disease, are assuming greater importance. We retrospectively examined the causes of death of HIV-seropositive patients at our institution in 1991, 1996, and 1998-1999. In 1998-1999, 11 (50%) of 22 deaths were due to end-stage liver disease, compared with 3 (11.5%) of 26 in 1991 and 5 (13.9%) of 36 in 1996 (P=.003). In 1998-1999, 55% of patients had nondetectable plasma HIV RNA levels and/or CD4 cell counts of >200 cells/mm(3) within the year before death. Most of the patients that were tested had detectable antibodies to hepatitis C virus (75% of patients who died in 1991, 57.7% who died in 1996, and 93.8% who died in 1998-1999; P=NS). In 1998-1999, 7 patients (31.8%) discontinued antiretroviral therapy because of hepatotoxicity, compared with 0 in 1991 and 2 (5.6%) in 1996. End-stage liver disease is now the leading cause of death in our hospitalized HIV-seropositive population.

Changes in health status and quality of life and the impact of uncertainty in patients who survive life-threatening arrhythmias.

OBJECTIVE: The purpose of this study was to describe the changes in perception of health status and quality of life from before treatment to 6 months after and the impact of uncertainty on these variables in survivors of life-threatening arrhythmia. DESIGN AND SETTING: A descriptive correlational design at a large urban teaching hospital. MEASURES: We measured health status, quality of life, and uncertainty before treatment and 6 months after a life-threatening arrhythmia. RESULTS: Survivors included 66 men and 15 women, 41 of whom received pharmacologic therapy and 36 of whom received an implantable cardioverter defibrillator (ICD), completed the Medical Outcomes Survey (SF-36), Ferrans and Powers Quality of Life Index (QLI), and the Mishel Uncertainty in Illness Scale (MUIS-C) before treatment and 6 months after. There were significant improvements in the mental and physical health composite summaries as measured by the SF36 (P <.01). Conversely, there were significant reductions in the overall score and specifically in socioeconomic and psychological/spiritual quality of life domains as measured by the QLI (P <.05). An increased perception of uncertainty was related to decreased perception of health status and quality of life at both measurement times, with higher correlations 6 months later. CONCLUSIONS: Survivors demonstrated improvements in perceived health status, although this did not appear to translate into improvements in the subjective domains of quality of life. The overall quality of life and the domains of psychological/spiritual state and socioeconomic status were lower 6 months after a life-threatening arrhythmia. Uncertainty had a significant impact on these perceptions, identifying an area for nursing interventions.

Mechanism of sustained monomorphic ventricular tachycardia in systemic sclerosis.

Three patients with advanced systemic sclerosis and recurrent or incessant monomorphic ventricular tachycardia underwent cardiac electrophysiologic studies. Biventricular transcatheter mapping showed findings most compatible with a reentrant mechanism, which was effectively treated with transcatheter ablation.

Antiarrhythmic drug therapy in patients with renal failure, liver failure, and congestive heart failure.

Commonly prescribed antiarrhythmic agents--and several recently developed agents--are reviewed with respect to their use in patients with renal failure, hepatic failure, and congestive heart failure. Because removal of electrophysiologically active agents from the systemic circulation in most cases depends on either renal elimination, hepatic metabolism, or both, patients with preexisting kidney or liver disease may be at increased risk of treatment-related drug toxicity, including proarrhythmia. These susceptibilities should be anticipated, with drug selection and/or dosage modified accordingly. Patients with left ventricular dysfunction and heart failure also are at increased risk of treatment-related complications, including proarrhythmia and hemodynamic intolerance. In addition, the metabolism of antiarrhythmic drugs may be impaired in these patients. Preference should be given to drugs with a proven safety profile, such as amiodarone, in patients with heart failure.

Runaway pacemaker in an implantable cardioverter defibrillator.

INTRODUCTION: Runaway pacemaker is a potentially catastrophic complication of any permanent pacing system. METHODS AND RESULTS: A 70-year-old man was found to have erratic behavior of his implantable cardioverter defibrillator (ICD) during a routine outpatient interrogation. His device was turned off, and he was hospitalized in preparation for a pulse generator replacement. During his hospitalization, his ICD unexpectedly began pacing rapidly. Despite prompt resuscitation attempts, the patient died. Postmortem examination of the device demonstrated a crystal oscillator failure. CONCLUSION: A previously unrecognized component malfunction is a potentially lethal complication of ICDs.

Antiarrhythmic drug therapy in pregnancy and lactation.

Antiarrhythmic agents commonly used in clinical practice are reviewed with respect to their potential for teratogenic or other adverse fetal effects. Although most experience with antiarrhythmic drug therapy during pregnancy has accrued with digoxin, quinidine, and propranolol, other antiarrhythmic agents may also be used in the pregnant patient if indicated. The choice of antiarrhythmic drug depends on the specific arrhythmia being treated, the cardiac condition of the patient or fetus, and the known or anticipated actions of the antiarrhythmic drug being considered. The management of specific arrhythmias encountered in pregnant women are also discussed. For benign arrhythmias, a conservative approach starting first with preventive measures is appropriate. For more severe or symptomatic arrhythmias, pharmacologic therapy should be instituted using drugs with proven safety to the fetus, if possible. Electrical cardioversion of the patient may be performed with relative safety in more emergent situations.

Reproducible induction of "atypical" torsades de pointes by programmed electrical stimulation: a novel form of sotalol-induced proarrhythmia?

We present a patient with sotalol-induced polymorphic ventricular tachycardia that was seen only with programmed ventricular stimulation. Electrophysiologic studies performed prior to initiation of sotalol therapy revealed inducible monomorphic ventricular tachycardia. Possible underlying electrophysiologic mechanisms are discussed.

The treatment of patients with infected implantable cardioverter-defibrillator systems.

OBJECTIVE: The purpose of this study was to evaluate the treatment of patients with infected implantable cardioverter-defibrillator systems. METHODS: Retrospective analysis was done of the cases of 21 patients treated for implantable cardioverter-defibrillator infection during an 11-year period. RESULTS: Of 723 cardioverter-defibrillator implantations (550 primary implants, 173 replacements), nine (1.2%) were complicated by early postoperative device-related infections. Late infections developed in two patients 19 and 22 months, respectively, after implantation. Ten other patients were transferred to our institution for treatment of cardioverter-defibrillator infection. The time from implantation to overt infection was 2.2 +/- 1.3 months, excluding the two late infections. The responsible organisms were Staphylococcus aureus (9), Staphylococcus epidermidis (6), Streptococcus hemolyticus (1), gram-negative bacteria (3), Candida albicans (1), and Corynebacterium (1). All patients were treated with intravenous antibiotic drugs. Total system removal was done in 15 patients and partial removal in 2; in 4, the cardioverter-defibrillator system was not explanted. There were no perioperative deaths. A new implantable cardioverter-defibrillator system was reimplanted in 7 patients after 2 to 6 weeks of antibiotic therapy. Ten patients were treated without reimplantation (2 arrhythmia operation, 8 antiarrhythmic drugs). Four patients (3 patients without explantation and 1 with partial system removal) were treated with maintenance long-term antibiotic therapy. During a mean follow-up of 21 +/- 2.8 months, no patient had clinical recurrence of infection. One patient treated with antiarrhythmic drugs without system reimplantation died suddenly. CONCLUSIONS: Infections that involve implantable cardioverter-defibrillator systems can be safely managed by removing the entire system with reimplantation after intravenous antibiotic therapy. In selected patients in whom the risk for system explantation is high and anticipated life expectancy is short, long-term antibiotic therapy to suppress low-virulence infections may represent an acceptable alternative.