To evaluate the effect of pegylated interferon maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy.
This is a meta-analysis of 6 randomized controlled trials ...that met the eligibility criteria. In all, 2438 chronic hepatitis C patients who failed to achieve sustained virologic response after initial treatment with pegylated interferon and ribavirin (antiviral therapy nonresponders or relapsers) were enrolled; 1237 patients received maintenance therapy (Maintenance group) and 1201 received no treatment (Observation group).
The pooled analyses found that patients in the Maintenance group had a significantly higher rate of normal alanine aminotransferase than did patients in the Observation group (pooled odds ratio OR 4.436, 95% confidence interval CI 1.225-16.064, P = .023), but there was no significant difference between the 2 groups in the incidence of hepatocellular carcinoma (pooled OR 0.872, 95% CI 0.501-1.519, P = .630), or the mortality rate (pooled OR 1.564, 95% CI 0.807-3.032, P = .185).
Interferon-based maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy improved liver inflammation as indicated by blood chemistry (alanine aminotransferase).
Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are ...limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g,
< 0.001) and β2-microglobulin-to-creatinine ratio (165 versus 83 μg/g,
< 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all
< 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch.
Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.
•Dolutegravir + boosted protease inhibitor is recommended as salvage therapy for highly experienced HIV-positive patients.•Evidence for the two-drug regimen of DTG + bPI is limited.•DTG + bPI ...demonstrated high efficacy and genetic barrier to resistance for patients with multiple resistance.•The two-drug regimen had metabolic impact on increased level of total cholesterol and low-density lipoprotein cholesterol.•Weight gain of 1.3 kg and 2.8 kg was noted after switching to the two-drug regimen at Weeks 24 and 48, respectively.
Real-world experience with dolutegravir (DTG) plus boosted protease inhibitor (bPI) as a two-drug regimen is limited for highly experienced HIV-positive patients with virological failure or intolerance to antiretroviral therapy. Patients receiving DTG plus bPI between September 2016 and June 2019 at 15 designated hospitals for HIV care in Taiwan were retrospectively included in this study. A standardised case record form was used to collect clinical data. The primary endpoint was virological response, defined as achieving or maintaining plasma HIV-RNA <50 copies/mL at Week 48. A total of 77 patients were included; 58 (75.3%) had documented genotypic resistance to 1–4 antiretroviral classes. The most commonly used PI was darunavir (87.0%; 67/77). Seven patients (9.1%) had no virological data at Week 48, including three with loss to follow-up, one severe hyperlipidaemia, one renal failure and cardiovascular disease, one superimposed HBV infection and one death from anal cancer. The virological response rate increased from 59.7% at baseline to 90.9% at Week 24 and 85.7% at Week 48. The only patient (1.3%) with virological failure at Week 48 had poor adherence and baseline low-level resistance to darunavir with resistance-associated mutations at M46L, I50V and V82A. Compared with baseline, mean total cholesterol increased by 20.1 mg/dL and weight by 2.8 kg at Week 48, while the estimated glomerular filtration rate decreased by 14.4 mL/min/1.73m2 (both P < 0.05). We conclude that a two-drug regimen containing DTG plus bPI was effective in highly-experienced HIV-positive patients, but metabolic impact and weight gain should be closely monitored.
•Candida tropicalis is the most common non-albicans species causing candidaemia.•C. tropicalis has a higher azole resistance rate than other Candida species.•51 of 56 fluconazole-resistant C. ...tropicalis belonged to the same genotype.•There was no evidence of patient-to-patient transmission.•Patients may acquire fluconazole-resistant C. tropicalis from the environment.
To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain.
By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients’ blood samples for Taiwan researchers ...and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.
Effectiveness of single-dose azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients has rarely been evaluated in the era of combination ART.
Consecutive HIV-infected ...patients with early syphilis, who received 2 g single-dose azithromycin or 2.4 MU benzathine penicillin G, between 2007 and 2014, were prospectively observed. Genotypic resistance to macrolides was determined in Treponema pallidum isolates identified from clinical specimens using PCR assays. Rapid plasma reagin (RPR) titres were determined at baseline and every 3 months after treatment. Primary outcome was a decline of RPR titre by ≥4-fold at 12 months after treatment.
During the study period, 162 HIV-infected patients with early syphilis received benzathine penicillin G and 237 patients received azithromycin. At 12 months follow-up, the serological response rate for penicillin and azithromycin groups was 61.1% and 56.5% (P = 0.41), respectively; respective response rate was 61.1% and 65.9% (P = 0.49) if we only included patients infected with T. pallidum not harbouring macrolide resistance in the azithromycin group. In multivariate analysis, RPR titres ≥1:32 (OR 2.56; 95% CI 1.55-4.21) and prior syphilis (OR 0.54; 95% CI 0.35-0.81) were predictors of serological response. Most common adverse effects of azithromycin included diarrhoea (52.7%), nausea (22.4%), abdominal pain (18.6%), bloating (17.7%) and lassitude/somnolence (27.4%).
In the setting of a low prevalence of macrolide-resistant T. pallidum, 2 g single-dose azithromycin achieved a similar serological response to benzathine penicillin G in HIV-infected patients with early syphilis. Major adverse effects of azithromycin were gastrointestinal symptoms and lassitude/somnolence.
We present a rare male fetus with karyotype of mosaic 45,X that comprises two types of aberrant Y chromosomes arising de novo (Yq12 deletion and isodicentric Yq11.22). Both types of the aberrant Y ...chromosomes lack the AZFc region which are expected to result in oligospermia but unaffected male external genitalia. Genetic analyses by karyotyping, chromosome microarray (CMA), and multiplex ligation-dependent probe amplification (MLPA) for the fetus revealed conflicting results. Additional molecular cytogenetics tools including fluorescence in situ hybridization (FISH) and multicolor banding (mBAND) were performed, which help resolving the discrepancy and delineated the composition of the aberrant Y chromosomes. This report highlighted the importance of incorporating multiple genetic technologies for accurate characterization of complex chromosomal rearrangements, which aid in the prenatal diagnosis and genetic counseling.
Abstract Background The aim of this study was to identify predictors of treatment failure of percutaneous catheter drainage (PCD) in patients with hepatobiliary-pancreatic cancer with pyogenic liver ...abscess (PLA). Methods Medical records of 44 patients with PLA with underlying hepatobiliary-pancreatic cancer who underwent PCD under computed tomographic guidance as primary treatment between January 2001 and December 2010 were collected and reviewed. Included patients were diagnosed with cholangiocarcinoma (n = 16), hepatocellular carcinoma (n = 12), pancreatic carcinoma (n = 9), carcinoma of the ampulla of Vater (n = 6), and gallbladder cancer (n = 1). The clinical factors related to failure of PCD were determined using logistic regression. Results The median age of the 44 patients with PLA was 68 years, and 48% were men. PCD failed in 15 patients (34%). Of the 15 patients with PCD failure, 12 subsequently required surgical intervention because of either clinical deterioration or imaging that demonstrated failure of abscess resolution with PCD. Three of these patients died with the initial drain in place before resolution of the abscess. In patients requiring surgery after PCD failure, the frequency of cure or abscess resolution reached 67%. Fourteen patients (32%) died during hospitalization. Multivariate analysis identified that multiloculated abscesses ( P = .005) and abscesses with biliary communication ( P = .036) were associated with failure of PCD. Conclusions Multiloculated abscesses and lesions with biliary communication pose a greater likelihood of failure of PCD in patients with hepatobiliary-pancreatic cancer with PLA. Early surgical intervention after PCD failure should be considered for these patients.
To compare the prevalence of potentially inappropriate medications (PIMs) using the 2012 and 2003 Beers Criteria in frail older patients receiving home health care services (HHS), and to explore the ...correlates of PIMs based on the 2012 Beers criteria.
A total of 145 older patients (mean age, 80.9 ± 7.6 years) with Barthel scale ≤ 60 receiving regular HHS from a university hospital between January 2013 and June 2013 were retrospectively enrolled. The 2003 and 2012 Beers criteria were used separately to detect PIMs. Logistic regressions, receiver-operating-characteristic curve analyses and number needed to harm were used, where appropriate.
The 2012 Beers Criteria identified more PIM cases than did the 2003 Beers Criteria (66.9% versus 55.9%, P < 0.05). Multivariate analysis revealed that PIM identified by the 2012 Beers Criteria was associated with an increased number of medications prescribed (P = 0.019) and the presence of psychiatric diseases (P = 0.001). Moreover, the area under the receiver-operating-characteristic curve for the number of drugs to predict the risk of PIM was 0.674 (P < 0.001) with the optimal cutoff value of 6 medications. After adjusting for age, sex, Charlson comorbidity index and psychiatric disorders, patients taking ≥6 drugs (adjusted odds ratio, 2.33; adjusted number needed to harm, 3.93; P < 0.05) had a significantly higher risk for PIM than those taking <6 drugs.
Our data showed that the 2012 Beers Criteria was more sensitive in detecting PIMs than the 2003 Beers Criteria. Furthermore, frail older patients receiving HHS with polymedication and with psychiatric illnesses had higher risk of PIM when using the 2012 criteria. The number of medications prescribed could be a useful index for risk stratification, and at the same time help physicians to be aware of the high risk for PIM when prescribing 6 or more drugs to frail older adults during in-home visits.
Abstract Objectives The purpose of this study was to explore the predictor index of mortality in patients with pyogenic liver abscess (PLA). Methods We performed a retrospective review that enrolled ...431 patients 18 years and older hospitalized due to PLA between January 2005 and December 2010. Clinical characteristics, laboratory results, treatments, and outcomes retrieved from medical records were analyzed. Multiple logistic regression and receiver operating characteristic curve analyses were performed. Results The mean age of the 431 patients identified with PLA was 56.9 ± 15.0 years. The mean Mortality in Emergency Department Sepsis (MEDS) score on admission was 4.8 ± 4.1 (range, 0-17). During hospitalization, 94 patients (22%) required intensive care. Of the 431 patients, 63 died, yielding a 15% case fatality rate. Multivariate analysis revealed that higher MEDS scores on admission ( P < .0001) and the presence of underlying malignancy ( P = .006), multiple abscesses ( P = .001), anaerobic infections ( P < .0001), hyperbilirubinemia ( P < .0001), and higher serum creatinine levels ( P < .0001) were significantly associated with PLA mortality. The estimated area under the receiver operating characteristic curve for MEDS in predicting PLA mortality was 0.829 (95% confidence interval, 0.791-0.864; P < .0001). The optimal cutoff MEDS value of 7 or higher had a sensitivity of 76% sensitivity and a specificity of 81%, with a 10.7-fold PLA mortality risk ( P < .0001) and a 26.2-fold intensive care unit admission risk ( P < .0001). Conclusions The MEDS scores on admission represent a significant prognostic indicator for patients with PLA.