Real-world impact of ivacaftor in people with cystic fibrosis and select ivacaftor-responsive mutations.

Background: Ivacaftor approval was extended to people with cystic fibrosis (CF) with ≥1 of 28 additional ivacaftor-responsive mutations in the USA in 2017 based on preclinical in vitro data. This retrospective, observational study assessed real-world clinical response to ivacaftor in people with CF with ≥1 of these mutations, using data from the US Cystic Fibrosis Foundation Patient Registry.

Methods: Participants aged ≥2 years with ≥1 of 28 eligible mutations initiating ivacaftor between May 2017 and December 2018 were included.

Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis.

Background: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF.

Methods: In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight.

Transseptal Mitral Valve-in-Valve-in-Valve.

• Transseptal MV implantation is performed for many indications. • Previous ViV procedures do not preclude further ViV insertion. • Appropriate sizing of transseptal MVs is essential to reduce complications.

Effectiveness of lumacaftor/ivacaftor initiation in children with cystic fibrosis aged 2 through 5 years on disease progression: Interim results from an ongoing registry-based study.

Background: Lumacaftor/ivacaftor (LUM/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) ≥1 year of age. To assess the impact of early LUM/IVA initiation on CF disease progression, a 6-year observational study leveraging data from existing CF patient registries is being conducted in children with CF homozygous for F508del (F/F genotype) who were aged 2 through 5 years at treatment initiation. Here we present interim results from this study focusing on data from the European CF Society Patient Registry (ECFSPR).

Surgical or Percutaneous Repair of Sinus of Valsalva Rupture: Case Series and Literature Review.

The rupture of the sinus of the Valsalva aneurysm is a rare but very serious condition. Rapid and accurate diagnosis and prompt treatment are critical for these cases. We present two cases of sinus of Valsalva ruptures.

Registry-based study in people with cystic fibrosis and an variant treated with ivacaftor.

Background: Ivacaftor approval was extended to people with cystic fibrosis (CF) and an variant in 2014 in the USA. This observational, real-world, postapproval study evaluated long-term outcomes among people with CF and an variant on ivacaftor using data from the US Cystic Fibrosis Foundation Patient Registry.

Methods: Key outcomes were evaluated in ivacaftor-treated people with CF and an variant for up to 36 months before and after treatment initiation using within-group comparisons.

Long-term tezacaftor/ivacaftor safety and efficacy in people with cystic fibrosis and an F508del-CFTR mutation: 96-week, open-label extension of the EXTEND trial.

Background: Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A. Here we report results from Part B, which evaluated safety and efficacy for an additional 96 weeks.

A Phase 3, Open-Label Study of Lumacaftor/Ivacaftor in Children 1 to Less Than 2 Years of Age with Cystic Fibrosis Homozygous for .

Previous phase 3 trials showed that treatment with lumacaftor/ivacaftor was safe and efficacious in people aged ⩾2 years with cystic fibrosis (CF) homozygous for the mutation in (CF transmembrane conductance regulator) (/ genotype). To assess the safety, pharmacokinetics, and pharmacodynamics of lumacaftor/ivacaftor in children aged 1 to <2 years with the / genotype. This open-label, phase 3 study consisted of two parts (part A [ = 14] and part B [ = 46]) in which two cohorts were enrolled on the basis of age (cohort 1, 18 to <24 mo; cohort 2, 12 to <18 mo).

Nonpoint source arsenic contamination of soil and groundwater from legacy pesticides.

Arsenic (As) contamination in wells is common throughout the northeastern United States. It is well documented that lead-arsenate (PbHAsO ) pesticides were widely used on fruit tree orchards from the 1890s to 1950s. This study evaluates the potential for As contamination of groundwater from former orchards in Connecticut, where there were over 47,000 orchards in 1935.

A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation.

Background: Tezacaftor (TEZ)/ivacaftor (IVA) is an approved CFTR modulator shown to be efficacious and generally safe and well tolerated in people ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous for the F508del-CFTR mutation and a residual function mutation. Although previous studies with IVA alone showed clinical benefits in people with CFTR gating mutations, TEZ/IVA has not yet been evaluated in a Phase 3 study of participants heterozygous for F508del-CFTR and a gating mutation (F/gating genotypes). Here, we present results from a randomized, double-blind, IVA-controlled, parallel-group, Phase 3 study assessing the efficacy, safety, and pharmacokinetics (PK) of TEZ/IVA in participants ≥12 years of age with F/gating genotypes.

G970R-CFTR Mutation (c.2908G>C) Results Predominantly in a Splicing Defect.

In previous work, participants with a G970R mutation in cystic fibrosis transmembrane conductance regulator (CFTR) (c.2908G>C) had numerically lower sweat chloride responses during ivacaftor treatment than participants with other CFTR gating mutations. The objective of this substudy was to characterize the molecular defect of the G970R mutation in vitro and assess the benefit of ivacaftor in participants with this mutation.

Deliberate Practice in Simulation-Based Surgical Skills Training: A Scoping Review.

Background: In recent years there has been a shift from traditional Halstedian methods toward more simulation-based medical education (SBME) for developing surgical skills. Questions remain about the role and value of SBME, although feedback and engagement in repetitive practice have been associated with positive learning outcomes. Regardless of approach, the principles of deliberate practice align with both the Halstedian traditions and ways of implementing SBME.

Use of bacteria community analysis to distinguish groundwater recharge sources to shallow wells.

In this study, bacteria community analysis was performed to supplement a preexisting evaluation of nitrate contamination in drinking water wells at a coastal site in Old Lyme, CT. Given well usage and coastal hydrogeologic conditions, the source(s) of nitrate contamination in domestic wells could not be discerned between local septic systems or a nearby farm where organic fertilizers were used. Groundwater bacteria communities are known to be sensitive to a variety of environmental conditions.

Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial.

We previously reported that ivacaftor was safe and well tolerated in cohorts aged 12 to <24 months with cystic fibrosis and gating mutations in the ARRIVAL study; here, we report results for cohorts aged 4 to <12 months. To evaluate the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in infants aged 4 to <12 months with one or more gating mutations. ARRIVAL is a single-arm phase 3 study.

Long-Term Ivacaftor in People Aged 6 Years and Older with Cystic Fibrosis with Ivacaftor-Responsive Mutations.

Introduction: Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) affect the quantity and/or function of CFTR protein reaching the cell surface. Ivacaftor, a CFTR potentiator that enhances chloride transport, increases the channel-open probability of normal and dysfunctional CFTR. Initially approved for people with CF (pwCF) with G551D-CFTR gating mutations, ivacaftor demonstrated clinical benefit in pwCF with other gating mutations and certain residual function mutations, including R117H-CFTR, in clinical studies.

Development and decay of procedural skills in surgery: A systematic review of the effectiveness of simulation-based medical education interventions.

Context: Changes to surgical training programmes in the UK has led to a reduction in theatre time for trainees, and an increasing reliance on simulation to provide procedural experience. Whilst simulation offers opportunity for repetitive practice, the effectiveness of simulation as an educational intervention for developing procedural surgical skills is unclear.

Methods: A systematic literature review was undertaken to retrieve all studies describing simulation-based medical education (SBME) interventions for the development of procedural surgical skills using the MEDLINE, PsycINFO, CINAHL, EMBASE and PUBMED databases.

Real-World Outcomes Among Patients with Cystic Fibrosis Treated with Ivacaftor: 2012-2016 Experience.

Introduction: In this long-term, postapproval, observational study, data from the US Cystic Fibrosis Foundation Patient Registry and the UK Cystic Fibrosis Registry were used to evaluate the impact of ivacaftor treatment on cystic fibrosis (CF) by comparing outcomes in ivacaftor-treated patients with those in matched untreated comparator patients. Registry data from up to 5 years of ivacaftor availability in the US and up to 4 years of availability in the UK were evaluated.

Methods: Starting in the first year of ivacaftor availability, ivacaftor-treated patients in each registry were matched 1:5 to comparator patients who never received ivacaftor.

Identifying the World Health Organization's fifth moment for hand hygiene: Infection prevention in the operating room.

Background: The World Health Organization have designed the fifth of their '5 moments' for hand hygiene to account for microbial transfer from patients to equipment in a narrow area around that patient, known as the patient zone. The study was prompted by emerging local confusion about application of the patient zone in the operating room (OR).

Aim/objectives: In two phases, we aimed to create a '5 moments' style poster displaying an OR patient zone: phase 1, quantify equipment, in direct contact with the patient and, touched by non-scrubbed staff immediately after touching the patient; and phase 2, categorise equipment identified in phase 1 into patient zone and healthcare zone.

Ivacaftor in cystic fibrosis with residual function: Lung function results from an N-of-1 study.

Background: Ivacaftor shows benefit in patients with cystic fibrosis (CF) and CFTR mutations associated with residual CF transmembrane conductance regulator (CFTR) function. Here we further assess the effect of ivacaftor in such patients using an N-of-1 study design.

Methods: Patients aged ≥12 years with CF with clinical or molecular evidence of residual CFTR function were randomized to 1 of 4 treatment sequences for two 4-week, double-blind crossover cycles (each divided into 2 weeks of ivacaftor treatment and placebo) followed by 8 weeks of open-label ivacaftor treatment.

Improving resource utilisation and outcomes after total knee arthroplasty through technology-enabled patient engagement.

Background: A multi-modal, technology-enabled, patient engagement and pathway management solution (PES) for patients undergoing primary total knee arthroplasty (TKA) was evaluated. The primary outcome measure was length of stay (LoS). The secondary outcome measures were clinical and patient-reported outcomes (PROMs).

Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries.

Background: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years.

Methods: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity.

An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).

Background: KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI.

Methods: Children received age- and weight-based ivacaftor dosages for 84 weeks.

Impact of MSSA screening on rates of surgical site infection following lumbar spine surgery.

Purpose: Methicillin-sensitive Staphylococcus aureus (MSSA) carriage may confer a significant risk of surgical site infection (SSI) and is common amongst the UK population. Screening for MSSA is not routinely offered to patients in the UK. Primary aim was to review the impact of introducing a MSSA screening programme, in addition to established Methicillin-resistant Staphylococcus aureus (MRSA) screening, on the incidence of SSIs following lumbar spine surgery.

Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study.

Background: Ivacaftor is generally safe and effective in patients aged 2 years and older who have cystic fibrosis and specific CFTR mutations. We assessed its use in children aged 12 to <24 months.

Methods: The ARRIVAL study is a phase 3, single-arm, two-part, multicentre study.