Te Ara Waiora-Implementing human papillomavirus (HPV) primary testing to prevent cervical cancer in Aotearoa New Zealand: A protocol for a non-inferiority trial.

Background: Cervical cancer is caused by high-risk types of human papillomavirus (HPV). Testing for high-risk HPV is a more sensitive screening method than cervical cytology for detecting cervical changes that may lead to cancer. Consistent with recent evidence of efficacy and acceptability, Aotearoa New Zealand plans to introduce HPV testing as the primary approach to screening, replacing cervical cytology, from mid-2023.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

Background: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI).

Purpose: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms.

Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020.

Temporal clustering of Kawasaki disease cases around the world.

In a single-site study (San Diego, CA, USA), we previously showed that Kawasaki Disease (KD) cases cluster temporally in bursts of approximately 7 days. These clusters occurred more often than would be expected at random even after accounting for long-term trends and seasonality. This finding raised the question of whether other locations around the world experience similar temporal clusters of KD that might offer clues to disease etiology.

Carbon Dioxide Absorption During Inhalation Anesthesia: A Modern Practice.

CO2 absorbents were introduced into anesthesia practice in 1924 and are essential when using a circle system to minimize waste by reducing fresh gas flow to allow exhaled anesthetic agents to be rebreathed. For many years, absorbent formulations consisted of calcium hydroxide combined with strong bases like sodium and potassium hydroxide. When Sevoflurane and Desflurane were introduced, the potential for toxicity (compound A and CO, respectively) due to the interaction of these agents with absorbents became apparent.

Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns.

Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

Background: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT).

Methods: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models.

Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease.

Background: Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1-6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5).

Methods: Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8-16 weeks, were included.

The effect of isocapnic hyperventilation on early recovery after remifentanil/sevoflurane anesthesia in O /air: A randomized trial.

Background: Isocapnic hyperventilation (ICHV) may hasten emergence from general anesthesia but remains inadequately studied. We prospectively determined emergence time after sevoflurane anesthesia of variable duration with and without ICHV.

Methods: In 25 ASA I-II patients, general anesthesia was maintained with one age-adjusted MAC sevoflurane in O /air and target-controlled remifentanil delivery.

Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy.

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST.

Methods: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries.

Short-Duration AL-335, Odalasvir, With or Without Simeprevir, in Patients With HCV GT1 or 3 Infection Without Cirrhosis.

This open-label, phase IIa study assessed the safety, pharmacokinetics, and efficacy of direct-acting antiviral agent (DAA) regimens in patients with chronic hepatitis C virus (HCV) infection. Multiple 6-12-week oral regimens of 400-800 mg once daily (QD) AL-335 + 50 mg QD/every other day odalasvir ± 75-150 mg QD simeprevir were evaluated in treatment-naïve, HCV genotype (GT)1/3-infected patients without cirrhosis. Safety/pharmacokinetic parameters, HCV-RNA, and sequencing data were assessed.

Are Short Subspecialty Courses the Educational Answer?

There is an urgent need to train more anesthesia providers in low- and middle-income countries (LMICs). There is also a need to provide more educational opportunities in subspecialty areas of anesthetic practice such as trauma management, pain management, obstetric anesthesia, and pediatric anesthesia. Together, these subspecialty areas make up a large proportion of the clinical workload in LMICs.

Education: The Heart of the Matter.

There are inadequate numbers of anesthesia providers in many parts of the world. Good quality educational programs are needed to increase provider numbers, train leaders and teachers, and increase knowledge and skills. In some countries, considerable external support may be required to develop self-sustaining programs.

Quality Indicators for Global Benchmarking of Localized Prostate Cancer Management.

Purpose: We sought to develop a core set of clinical indicators to enable international benchmarking of localized prostate cancer management using data available in the TrueNTH Global Registry.

Materials And Methods: An international expert panel completed an online survey and participated in a face-to-face meeting. Participants included 3 urologists, 3 radiation oncologists, 2 psychologists, 1 medical oncologist, 1 nurse and 1 epidemiologist with prostate cancer expertise from a total of 7 countries.

The emergence of NS5B resistance associated substitution S282T after sofosbuvir-based treatment.

S282T in NS5B is the primary amino acid substitution associated with resistance to sofosbuvir (SOF) but has rarely been detected in patients treated with a SOF-based regimen. Here, the emergence and fitness of the S282T substitution in virologic failure patients administered SOF-based regimens across the SOF and ledipasvir (LDV)/SOF phase 2 and 3 programs was evaluated. Plasma samples collected at baseline and at virologic failure were amplified and deep sequenced (1% cutoff).

Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection.

Background: Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.

Methods: We conducted two phase 3, randomized, open-label, multicenter trials.

Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen.

Unlabelled: The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct-acting antiviral-based therapies remains unclear. In this multicenter, open-label, phase 2 study, we evaluated the efficacy and safety of a fixed-dose combination of sofosbuvir-velpatasvir (400 mg/100 mg) plus weight-adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct-acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment.

Population-based study demonstrating an increase in colorectal cancer in young patients.

Background: New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened population. The aim of this study was to determine the trends in incidence and tumour location in the New Zealand population before the introduction of national colorectal cancer screening.

Methods: Data were obtained from the national cancer registry and linked to population data from 1995 to 2012.

Efficacy of Ledipasvir Plus Sofosbuvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2 Infection.

Background & Aims: Patients with chronic hepatitis C virus (HCV) genotype 2 have high rates of response to treatment with sofosbuvir and ribavirin. However, ribavirin is associated with hemolytic events and is poorly tolerated by some patients. We evaluated the effectiveness of sofosbuvir and ledipasvir in treatment-naïve and treatment-experienced patients with HCV genotype 2, comparing 12 versus 8 weeks of treatment.

A Diacylglycerol Transferase 1 Inhibitor Is a Potent Hepatitis C Antiviral in Vitro but Not in Patients in a Randomized Clinical Trial.

Hepatitis C virus (HCV) infection is a significant cause of liver disease affecting 80-150 million people globally. Diacylglycerol transferase 1 (DGAT-1), a triglyceride synthesis enzyme, is important for the HCV life cycle in vitro. Pradigastat, a potent DGAT-1 inhibitor found to lower triglycerides and HgbA1c in patients, was investigated for safety and efficacy in patients with HCV.