Successful use of generic direct acting antiviral medications to treat hepatitis C-a New Zealand-wide study.

AIMS: Direct acting antiviral (DAA) hepatitis C (HCV) medications are funded in New Zealand since 2016 for some and since 2019 for all genotypes. The purpose of this study was to review New Zealand-wide data of the use of generic HCV DAA medications imported through Tasmanian FixHepC Buyer's Club and the associated side effect profiles. METHODS: This is a retrospective data audit on the use of generic DAAs to treat HCV; outcomes from consecutive hepatitis C patients (naïve and pre-treated) treated with generic DAAs (sofosbuvir/ledipasvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, ribavirin) collected from all known sites that used Buyer's club medications in eight New Zealand district health board regions were summarised. Demographic, disease characteristics, FibroScan and blood markers' (platelets, ALT, GGT, AFP) data were collected. RESULTS: Study sample was 81.8% New Zealand European, 64.8% male of median 56.0 (IQR: 48.0-60.0) years old. Three participants (4.5%) were HIV positive. 74.7% of the participants had signs of fibrosis (F1-F4); 40.5% had cirrhosis/scaring (F4). 61.7% of the patients were naïve to treatment. 42.0%, 40.1% and 12.0% received sofosbuvir/ledipasvir, sofosbuvir/daclatasvir, sofosbuvir/velpatasvir, respectively; 32.1% also received ribavirin. 80.2% of patients received treatment for 12 weeks. 95.1% (154/162) of the sample achieved sustained virological response at 12 weeks post-treatment, 2.5% relapsed, 1.2% were lost to follow-up. The main minor side effects included fatigue, headache, difficulty sleeping, experienced by 21.7%, 7.0%, 7.0%, respectively. An average total cost for medication and monitoring was 2,027 to 2,659 NZD (12 weeks), and 3,054 to 4,260 NZD (24 weeks) per patient. CONCLUSIONS: Generic DAAs to treat hepatitis C are safe, efficient and a cheaper than branded medications option.

A liver health hui: hepatitis C knowledge and associated risk factors in New Zealand gang members and their families.

Hepatitis C virus (HCV) and B virus (HBV) infections are highly prevalent, with a high percentage of undiagnosed cases. Knowledge of HCV and its modes of transmission are essential for disease prevention and management. We studied a high-risk New Zealand gang population on viral hepatitis prevalence, their level of knowledge and the liver health risk factors in a community setting. Participants completed demographic, risk factor and knowledge questionnaires in three health meetings in New Zealand. Participants' blood samples were tested for HBV, HCV, biochemical indicators of liver disease. Liver fibrosis levels were assessed using a Fibroscan® device. We studied 52 adult Mongrel Mob members, affiliates and whanau (extended family) throughout New Zealand. We identified no HCV and two HBV cases, confirmed high-risk factor levels and poor associated knowledge, with a significant association between lack of knowledge and presence of specific risk factors. We successfully conducted a community-focused, high-risk, hard-to-reach gang population study, and found a link between lack of knowledge and risk factors for HCV infection. This study provided first-of-its-kind data on viral hepatitis in a gang population and demonstrated the need for educational screening programmes to aid early HCV detection, prevention and treatment.

Individual and environmental correlates of school-based recess engagement.

The purpose of this study was to examine individual variables associated with children's levels of recess physical activity (PA), as well as environmental influences that influence children's engagement during recess. Participants (n = 146) were 4-6th grade students across seven schools. PA data were collected using the Fitbit Flex. Psychological need satisfaction at recess data were collected with a basic psychological need satisfaction for recess PA survey. Observations of recess activity engagement and the quality of the recess environment were also collected at 134 recess periods (n = 8340 children) across nine schools. Results of multi-level regression analyses indicated that gender and recess time were significant predictors of physical activity during recess. In examination of the environmental level factors, multi-level regression analyses revealed that 'adult engagement and supervision' was the only significant predictor for recess engagement in boys and girls. These findings suggest the amount of time allocated, and the quality of the recess environment must be included in evaluation of the critical factors relevant to engagement of students in physically active recesses.

Prevalence and knowledge of hepatitis C in a middle-aged population, Dunedin, New Zealand.

AIM: To determine the prevalence of infection with hepatitis C virus (HCV) in those most at risk of advanced liver disease and to identify gaps in knowledge of HCV. METHODS: Questionnaires were mailed to randomly selected residents aged 40-59 to assess the extent of their general knowledge about HCV. The questionnaire assessed demographics, the extent of general knowledge about viral hepatitis, potential risks for infection and the prevalence of risk factors associated with increased progression of liver fibrosis. Anonymised residual laboratory blood samples from 40-59 years old people from Dunedin taken in hospital or in the community, were tested for HCV antibodies and alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT). Linear regression was performed to examine whether the demographics sex, age, socio-economic status, qualification level and occupation sector (categorical variables) were predictors of level of general knowledge about hepatitis. For the demographics that were found to be significant predictors of score outcome, multiple regression analysis was used to determine independent effects. χ (2) tests were used to compare our selected sample and our responder population demographics, to the demographics of the entire 40-59 years old population in Dunedin using the 2006 NZ census data. Exact confidence intervals for the proportion positive for HCV and HBV were calculated using the binomial distribution. RESULTS: The response rate to the mailed questionnaire was 431/1400 (30.8%). On average 59.4% questions were answered correctly. Predictors for higher scores, indicating greater knowledge about symptoms and transmission included sex (female, P < 0.01), higher level of qualification (P < 0.000) and occupation sector (P < 0.000). Sharing intravenous drug utensils was a known risk factor for disease transmission (94.4%), but the sharing of common household items such as a toothbrush was not. 93% of the population were unaware that HCV infection can be asymptomatic. 25% did not know that treatment was available in New Zealand and of those who did know, only 40% assumed it was funded. Six hundred and eighty-two residual anonymised blood samples were tested for HCV antibodies, ALT, AST and GGT. The prevalence for HCV was 4.01%, 95%CI: 2.6%-5.8%. Liver function tests were not useful for identifying likelyhood of HCV infection. CONCLUSION: Prevalence of HCV in our population is high, and the majority have limited knowledge of HCV and its treatment.

Use of pethidine for percutaneous liver biopsy - a randomised, placebo-controlled, double blind study.

BACKGROUND: Percutaneous liver biopsy (PLB) is the "gold standard" in the diagnosis of liver diseases. A pilot trial has shown pethidine may reduce anxiety and the need for post-procedural pain relief. The aim of this study was to investigate the role of pre-procedural pethidine. METHODS: A double-blinded, randomized, placebo-controlled trial was conducted to assess the need for pethidine prior to PLB. 98 patients were randomly assigned to receive either 50 mg pethidine i.v. (n = 48), or an equal volume of 0.9% normal saline (n = 50). PLB was performed with ultrasound guidance after adequate local anaesthesia with xylocaine. Patients were asked to self-evaluate pain experienced using a visual analogue score (0-10) immediately and an hour after PLB. Patients were then followed up 24 hours after the procedure to assess their pain score, retrospective pain score and willingness to have a repeat procedure. RESULTS: Pethidine administration resulted in significantly lower pain scores (0.60 ± 0.1 vs 1.2 ± 0.2, p = 0.006) and required less analgesia (0% vs 10%, p = 0.03) immediately after PLB in comparison to the placebo group. There was no significant difference in the pain score and analgesia requirement one hour after the procedure, the pain score at 24 hours after procedure and retrospective pain score. 94% of all patients of either group are willing to under go a repeat liver biopsy (NS). CONCLUSIONS: The administration of pethidine routinely prior to PLB reduces the immediate post procedural pain but has no lasting effect and does not influence the patients' decision making process for future investigations. TRIAL REGISTRATION: ACTRN12614001194651 , 13 November 2014.

Maternal Smoking Dysregulates Protein Expression in Second Trimester Human Fetal Livers in a Sex-Specific Manner.

CONTEXT: Maternal smoking during pregnancy has adverse effects on the offspring (eg, increased likelihood of metabolic syndrome and infertility), which may involve alterations in fetal liver function. OBJECTIVE: Our aim was to analyze, for the first time, the human fetal liver proteome to identify pathways affected by maternal smoking. DESIGN: Fetal liver proteins extracted from elective second trimester pregnancy terminations (12-16 weeks of gestation) were divided in four balanced groups based on sex and maternal smoking. SETTING AND PARTICIPANTS: Livers were collected from 24 morphologically normal fetuses undergoing termination for nonmedical reasons and analyzed at the Universities of Aberdeen and Glasgow. MAIN OUTCOME MEASURES: Protein extracts were resolved by 2D-PAGE and analyzed with SameSpots software. Ingenuity pathway analysis was used to investigate likely roles of dysregulated proteins identified by tandem liquid chromatography/mass spectroscopy. RESULTS: Significant expression differences between one or more groups (fetal sex and/or maternal smoking) were found in 22 protein spots. Maternal smoking affected proteins with roles in post-translational protein processing and secretion (ERP29, PDIA3), stress responses and detoxification (HSP90AA1, HSBP1, ALDH7A1, CAT), and homeostasis (FTL1, ECHS1, GLUD1, AFP, SDHA). Although proteins involved in necrosis and cancer development were affected in both sexes, pathways affecting cellular homeostasis, inflammation, proliferation, and apoptosis were affected in males and pathways affecting glucose metabolism were affected in females. CONCLUSIONS: The fetal liver exhibits marked sex differences at the protein level, and these are disturbed by maternal smoking. The foundations for smoke-induced post-natal diseases are likely to be due to sex-specific effects on diverse pathways.

Routine vs. expert-guided transvaginal ultrasound in the diagnosis of endometriosis: a retrospective review.

OBJECTIVE: The objective of this study is to evaluate the sensitivity of routine trans vaginal ultrasound (TVUS) compared to expert-guided transvaginal ultrasound (ETVUS) for the diagnosis of endometriosis. METHODS: A retrospective chart review performed at a Canadian tertiary center specializing in the diagnosis and management of endometriosis. All cases with surgically confirmed endometriosis and an ETVUS completed at a single center were included for review and compared to routine TVUS performed for the same indication. RESULTS: Forty cases met the inclusion criteria. Mean patient age of the study population at first surgical diagnosis was 31.2 ± 6.9 years. Dysmenorrhea (76.9 %) and chronic pelvic pain (74.3 %) were the most common presenting symptoms. Sensitivity of routine TVUS was 25 % (10/40), compared to 78 % (31/40) with ETVUS, (P < 0.01). Comparisons were made based on site of disease. Routine TVUS and ETVUS detected bladder involvement in (0/40) vs. 5 % (2/40); ureter (0/40) vs. 7.5 % (3/40); ovary 25 % (10/40) vs. 72.5 % (29/40); retrocervical area (0/40) vs. 60 % (24/40), rectosigmoid 5 % (2/40) vs. 77.5 % (31/40), respectively. Specific endometriotic lesions recognized by TVUS versus ETVUS, were: ovarian endometriomas in 25 % (10/40) vs. 45 % (18/40), adhesions leading to abnormal anatomy in 2.5 % (1/40) vs. 77.5 % (31/40); endometriotic implants or plaques in 2.5 % (1/40) vs. 70 % (28/40); and endometriotic nodules in 2.5 % (1/40) vs. 35 % (14/40), respectively. Routine TVUS diagnosis relied on the presence or absence of endometrioma (10/10), whereas ETVUS showed additional sites of disease in 97 % (30/31) patients. CONCLUSIONS: ETVUS is more sensitive than routine TVUS to diagnose endometriosis, identifying lesions other than endometrioma and is of assistance in surgical planning and patient counseling.

Dienogest for the treatment of deep endometriosis: case report and literature review.

A 38-year-old woman was found to have a deep 3.3-cm endometriotic nodule of the bladder, confirmed by cystoscopic resection and imaging. Ultrasound also confirmed a 2.6-cm vaginal fornix implant with similar appearance to the bladder mass. The patient's primary symptoms were mild dysmenorrhea, catamenial dysuria and hematuria. The patient conceived shortly after referral and 3 months post-delivery was offered surgical management but declined in favor of medical management. Dienogest 2 mg once a day was started and after 16 months of treatment, more than 50% reduction in the size of the bladder nodule was seen (pretreatment: 3.3 × 3.0 × 2.7 cm, volume: 13.9 cm(3) ; post-treatment: 2.8 × 2.3 × 1.0 cm, volume: 6.4 cm(3) ). The vaginal mass also decreased in size from a pretreatment value of 2.0 × 2.6 × 1.4 cm (3.8 cm(3) ) to 1.1 × 1.4 × 0.5 mm (0.40 cm(3) ) after the treatment. The patient remained asymptomatic with no significant adverse drug reaction during management. Dienogest may be one of the options for medical management of deep endometriosis in young women especially when surgical intervention is declined.

Home Availability and the Impact of Weekly Stressful Events Are Associated with Fruit and Vegetable Intake among African American and Hispanic/Latina Women.

Background. Mediating and moderating variables may interfere with the association between neighborhood availability of grocery stores (NAG) and supermarkets (NAS) and fruit and vegetable (FV) intake. Objective. The purpose of this study was to test mediation of home availability of FV (HAFV) and moderation of impact of weekly stressful events (IWSE) on the association between NAG and NAS with FV consumption among African American (AA) and Hispanic/Latina (HL) women. Methods. Three hundred nine AA and HL, 25-60 year old women in the Health Is Power (HIP) randomized controlled trial completed validated measures of HAFV, IWSE, and FV intake at baseline. Trained field assessors coded NAG and NAS. Institutional Review Board approval was obtained. Results. NAG and NAS were not associated with FV intake or HAFV, so HAFV was not a mediator. HAFV (std. Beta = .29, P < 0.001) and IWSE (std. Beta = .17; P < 0.05) were related to FV intake (R(2) = 0.17; P < 0.001), but IWSE was not a moderator. Conclusion. Increasing HAFV and decreasing the IWSE should increase FV consumption. The extent to which the neighborhood environment is related to the home food environment and diet, and the mechanisms for the association between IWSE and diet should be examined in future research.

Telehome monitoring in patients with cardiac disease who are at high risk of readmission.

Patients with chronic conditions are heavy users of the health care system. There are opportunities for significant savings and improvements to patient care if patients can be maintained in their homes. A randomized control trial tested the impact of 3 months of telehome monitoring on hospital readmission, quality of life, and functional status in patients with heart failure or angina. The intervention consisted of video conferencing and phone line transmission of weight, blood pressure, and electrocardiograms. Telehome monitoring significantly reduced the number of hospital readmissions and days spent in the hospital for patients with angina and improved quality of life and functional status in patients with heart failure or angina. Patients found the technology easy to use and expressed high levels of satisfaction. Telehealth technologies are a viable means of providing home monitoring to patients with heart disease at high risk of hospital readmission to improve their self-care abilities.

Prevalence and clinical implications of anemia in congestive heart failure patients followed at a specialized heart function clinic.

The objective of this study was to assess the prevalence of anemia and to investigate its association with comorbidities and its impact on clinical outcomes in patients with heart failure. The association of predefined anemia, as well as the correlation of serum hemoglobin level as a continuous variable, with outcomes of emergency department visits, hospitalization, and mortality was investigated. There were fewer anemic patients in New York Heart Association classes I and II than in classes III and IV. Anemia was associated with higher rates of emergency department visits, hospital admissions, and all-cause mortality. Multivariable analysis showed that anemia is independently associated with mortality. When hemoglobin level was considered as a continuous variable, the authors noted that the mortality risk correlated with hemoglobin level disappears when hemoglobin level exceeds 140 g/L. The authors conclude that anemia has strong impacts on functional class and other clinical outcomes in patients with heart failure.

Evaluation of the program to eliminate lymphatic filariasis in Vanuatu following two years of mass drug administration implementation: results and methodologic approach.

This report presents the results of the Vanuatu mid-term evaluation of the lymphatic filariasis elimination program being implemented countrywide. Vanuatu is one of the first countries to initiate this program as part of the Global Program for Elimination of Lymphatic Filariasis, based on a five-year annual mass drug administration (MDA) of albendazole and diethylcarbamazine and complemented in Vanuatu by extensive coverage with bed nets. This paper reports results of 561 persons tested at eight sentinel sites following two years of MDA. Coverage was 72% and bed net use was more than 70%. Antigen prevalence was reduced by 63% (from 22% to 8%) and prevalence of microfilaremia prevalence was reduced by 93% (from 12% to 0.8%). Results of surveys of health workers and the community are also reported, and the methodology used for this evaluation is discussed.

BNP-guided therapy not better than expert's clinical assessment for beta-blocker titration in patients with heart failure.

B-type natriuretic peptide (BNP) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure. Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels. The aim of this study is to compare the efficacy of a BNP-guided approach vs. standard care on beta-blocker titration in heart failure patients. Forty-one patients with heart failure were randomized into a clinical trial. Bisoprolol was started, and the dose was regularly up-titrated. BNP was measured monthly. The clinical group had beta-blocker dosage increased according to standard care, whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus standard care. The primary outcome was mean beta-blocker dose achieved after 3 months. BNP levels, left ventricular ejection fraction, clinical score, quality of life, and hospitalization were collected in all patients. BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD (5.9+/-4.3 mg vs. 4.4+/-3.4 mg, p=0.22). Left ventricular ejection fraction was significantly improved in both groups by 7.3% (95% confidence interval, 4.1%-10.4%; p<0.0001). A trend toward better quality of life was seen in the BNP group.

Effect of Orlistat in obese patients with heart failure: a pilot study.

Heart failure is the leading cause of hospitalization. Obesity is increasingly common and is a major public health problem. The aim of this study is to assess whether obese patients with heart failure can benefit from losing weight via an orlistat-assisted diet. This randomized clinical trial included obese patients with ejection fractions < or =40%. Orlistat and diet counseling were compared with diet counseling alone. Twenty-one consecutive obese patients with heart failure were recruited. Significant improvement in 6-minute walk test (45.8 m; 95% confidence interval, 5.2-86.4 m; p=0.031), functional class (-0.6+/-0.5, p=0.014), weight loss (-8.55 kg; 95% confidence interval, -13.0 to -4.1 kg; p<0.001) and also significant decreases in total cholesterol (p=0.017), low-density lipoprotein cholesterol (p=0.03), and triglycerides (p=0.036) were observed in the orlistat group. Orlistat can promote significant weight loss and symptoms of relief in obese patients with heart failure, as measured by 6-minute walk test and functional capacity. The lipid profile improved. Orlistat was safe and well tolerated.

Brain natriuretic peptide predicts successful cardioversion in patients with atrial fibrillation and maintenance of sinus rhythm.

BACKGROUND: Brain natriuretic peptide (BNP) is released from the heart by hemodynamically induced muscle stretch. Patients with atrial fibrillation have higher levels of BNP than those in sinus rhythm. OBJECTIVE: To assess the usefulness of BNP as a predictor of successful cardioversion in patients with persistent atrial fibrillation and subsequent maintenance of sinus rhythm. SUBJECTS AND METHODS: Twenty patients undergoing cardioversion for persistent atrial fibrillation were enrolled. BNP levels were measured before electric cardioversion, and 30 min and two weeks after cardioversion. Baseline echocardiograms and 12-lead electrocardiograms were obtained from all patients. Patients with valvular disease, previous mitral valve surgery or significant left ventricular dysfunction were excluded. RESULTS: The mean BNP level and the mean heart rate were significantly higher before cardioversion than 30 min after (197+/-132 pg/mL versus 164+/-143 pg/mL, P=0.02, and 77+/-17 beats/min versus 57+/-12 beats/min, P=0.0007, respectively). Patients who reverted back to atrial fibrillation after two weeks had a baseline BNP of 293+/-106 pg/mL, while those who remained in sinus rhythm for two weeks had a lower baseline BNP of 163+/-122 pg/mL (P=0.02). CONCLUSION: In patients with persistent atrial fibrillation, BNP levels are associated with successful cardioversion and maintenance of sinus rhythm two weeks after cardioversion.

Persistent orthopnea and the prognosis of patients in the heart failure clinic.

Heart failure (HF) is a public health problem with ever-growing costs. Signs such as jugular venous pressure and third heart sound have been associated with disease prognosis. Symptoms of heart failure are frequently subjective, and their real value is often overlooked. The authors aimed to assess the relationship between orthopnea and left ventricular ejection fraction (LVEF) and hospitalization rate in patients referred to the HF clinic. One hundred fifty-three new consecutive patients referred to the HF clinic from September 2001 to July 2002 were reviewed. Information about orthopnea was available at baseline and at a 6-month to 1-year follow-up. One hundred thirty-one patients had a baseline multigated radionuclide ventriculogram scan, and 68 patients had a follow-up multigated radionuclide ventriculogram scan available. The patients were divided into groups by presence of orthopnea and compared with respect to LVEF and hospitalization rate. Patients with or without orthopnea had similar LVEFs at baseline (32%+/-17% vs. 33%+/-15%, respectively; p=NS). However, patients who were orthopnea-free at the follow-up visit had a significant LVEF improvement whereas patients with ongoing orthopnea at follow-up had no LVEF improvement (11%+/-13% vs. -1%+/-6%; p<0.001). Patients who presented with persistent orthopnea had a significantly higher rate of hospitalization (64% vs. 15.3%; p=0.0001). Persistent orthopnea in HF patients is associated with a significantly higher rate of hospitalization and with worsening or no improvement in LVEF. Patients with persistent orthopnea may require a more aggressive approach to improve their outcome. This result may help centers with limited access to LVEF measurements to better stratify HF patients' risk.

Effect of bisoprolol on right ventricular function and brain natriuretic peptide in patients with heart failure.

Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of b blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective b-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking b blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7+/-14.3 years. Baseline RVEF was 30.7%+/-6.3% and baseline LVEF was 21.7%+/-9.4%. Mean bisoprolol dose reached was 5.3+/-3.9 mg daily. At 4 months, RVEF significantly increased by 7.1% (95% confidence interval, 3.9-10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%-11.9%; p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF.