The outcome of bone graft surgery for nonunion of fractures of the scaphoid.

Data on 806 patients undergoing bone graft surgery for a scaphoid fracture nonunion were retrospectively collected at 19 centres in the United Kingdom. Each centre contributed at least 30 cases. Sufficient data were available in 462 cases to study factors that influenced the outcome of surgery.

Awareness and Acceptability of pre-exposure prophylaxis (PrEP) among gay, bisexual and other men who have sex with men (GBMSM) in Kenya.

Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are significantly affected by HIV. Pre-exposure prophylaxis (PrEP) is an effective biomedical approach to HIV prevention. We conducted a cross-sectional survey of 459 HIV-negative Kenyan GBMSM to assess individual and interpersonal correlates of PrEP awareness/acceptability using univariate and hierarchical logistic regression modeling.

Morphology of the lateral fossa of the brain (sylvian valley): anatomo-radiological aspects and surgical application.

Introduction: The knowledge acquired on the lateral fossa of the brain (LFB) is heterogeneous and incomplete. Our goal was to provide a morphological description of the LFB and analyze the impact of these descriptions on the surgical approach of the region.

Methods: The morphology of LFB was studied on 40 cerebral hemispheres of 20 right-handed subjects aged 18-55 years with an MRI of 1.

Patient Carrying Time, Confidence, and Training with Epinephrine Autoinjectors: The RACE Survey.

Background: Limited real-world data exist regarding patient carrying compliance and confidence in using different types of epinephrine autoinjectors (EAIs).

Objective: To perform a Real-world Assessment of Patients' Carrying Time and Confidence with Epinephrine Autoinjector Devices (RACE survey).

Methods: This was a noninterventional survey of patients (≥7 years) who filled 1 or more prescription for Auvi-Q or EpiPen between January 2013 and January 2014.

The Clinical and Cost Effectiveness of Inotuzumab Ozogamicin for the Treatment of Adult Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited Pfizer, the manufacturer of inotuzumab ozogamicin (henceforth inotuzumab), to submit clinical- and cost-effectiveness evidence for inotuzumab as part of NICE's single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics, both at the University of York, were commissioned as the independent evidence review group (ERG). The clinical-effectiveness data were from a multicentre randomised controlled trial that compared inotuzumab with standard of care (SoC), where SoC was the investigator's choice of chemotherapy.

The impact of structural factors on diagnostic delay in diffuse large B-cell lymphoma.

Background: Reducing diagnostic delays in cancer has been a major interest worldwide; however, the literature on diagnostic delays in lymphoma remains scarce. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma. We aimed to determine whether certain structural factors predicted diagnostic delays in DLBCL and whether diagnostic delays impacted overall survival (OS).

Tenosynovial giant cell tumours of the hand: A multicentre case-control study.

Many factors have been proposed to contribute to the risk of recurrent tenosynovial giant cell tumours (TSGCT); however, we remain unable to predict those at risk, which formed the rationale for this multicentre retrospective case-control study of 28 patients with recurrence. We included cases of recurrence in a 1:1 ratio matched for age and sex with controls over 10 years. Using Cox regression, we present hazard ratios (HRs) for recurrence with 95% confidence intervals (CIs).

Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform.

According to the World Health Organization, more than 1 billion people are at risk of or are affected by neglected tropical diseases. Examples of such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all of which are prevalent in Africa, South America, and India. Our aim within the New Medicines for Trypanosomatidic Infections project was to use (1) synthetic and natural product libraries, (2) screening, and (3) a preclinical absorption, distribution, metabolism, and excretion-toxicity (ADME-Tox) profiling platform to identify compounds that can enter the trypanosomatidic drug discovery value chain.

A Case of Schizophrenia With Catatonia Resistant to Lorazepam and Olanzapine Monotherapy But Responsive to Combination Treatment: Is It Time to Consider Using Select Second-Generation Antipsychotics Earlier in the Treatment Algorithm for This Patient Type?

Objective: Catatonia is a distinct psychomotor syndrome that involves a constellation of up to 40 different symptoms. Although conventionally responsive to benzodiazepines, the catatonic syndrome is much more resistant to benzodiazepine treatment when a feature of schizophrenia.

Method: We present a patient with schizophrenia with catatonic symptoms, marginally responsive to lorazepam challenge, lorazepam, and olanzapine monotherapy, but ultimately began combination treatment with these 2 medications.

Allostery in Its Many Disguises: From Theory to Applications.

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems.

Functionalized Phenylbenzamides Inhibit Aquaporin-4 Reducing Cerebral Edema and Improving Outcome in Two Models of CNS Injury.

Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet.

Systematic review of fibrin glue in burn wound reconstruction.

Background: In the reconstruction of burns using split-skin grafts (SSGs), fibrin glue can be used to improve graft take and reduce haematoma formation, although the efficacy and cost-effectiveness are unknown. This systematic review evaluated outcomes of fibrin glue compared with conventional SSG attachment techniques. Outcomes of interest included SSG take, haematoma formation, patient satisfaction and cost-effectiveness.

Optimizing DIEP Flap Insetting for Immediate Unilateral Breast Reconstruction: A Prospective Cohort Study of Patient-Reported Aesthetic Outcomes.

Background: To improve the aesthetic outcome of deep inferior epigastric perforator (DIEP) flap breast reconstruction, flaps should be tailored to the patient's characteristics. A single method of DIEP flap insetting will not suffice for all women seeking breast reconstruction. The authors share the outcomes of a prospective longitudinal study on DIEP flap insetting and present an algorithm for reconstruction.

Influence of Transmembrane Helix Mutations on Cytochrome P450-Membrane Interactions and Function.

Human cytochrome P450 (CYP) enzymes play an important role in the metabolism of drugs, steroids, fatty acids, and xenobiotics. Microsomal CYPs are anchored in the endoplasmic reticulum membrane by an N-terminal transmembrane (TM) helix that is connected to the globular catalytic domain by a flexible linker sequence. However, the structural and functional importance of the TM-helix is unclear because it has been shown that CYPs can still associate with the membrane and have enzymatic activity in reconstituted systems after truncation or modification of the N-terminal sequence.

Molecular Modeling in Drug Design.

This Special Issue contains thirteen articles that provide a vivid snapshot of the state-of-the-art of molecular modeling in drug design, illustrating recent advances and critically discussing important challenges [...

Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients.

Background: This study evaluated the proportion of patients with atherosclerotic cardiovascular disease (ASCVD) and probable heterozygous familial hypercholesterolemia (HeFH) achieving ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) or reaching the LDL-C ≤70 mg/dL threshold, after initiating or modifying statin, and/or ezetimibe therapy.

Materials And Methods: Adult ASCVD patients with baseline LDL-C >70 mg/dL (index) and a subset of patients with probable HeFH (proxied by LDL-C ≥190 mg/dL) were identified between January 1, 2012, and August 31, 2014, from the IQVIA electronic medical record database. Patients were followed for 12 months pre-index to examine baseline lipid-lowering therapy (LLT) use, and 12 months post index to evaluate treatment modifications and post-treatment LDL-C levels, stratified by type of treatment received and LDL-C levels at baseline.

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.

Purpose: To describe patient characteristics and treatment patterns among early initiators of proprotein convertase subtilisin/kexin type nine inhibitors (PCSK9is) who initiated treatment within the first 6 months of market availability.

Patients And Methods: This retrospective cohort study used IQVIA's longitudinal open-source point-of-sale pharmacy claims database (LRx) and PharMetrics Plus (P+) health plan claims database to identify patients initiating a PCSK9i between January 1, 2016 and June 30, 2016. The index date was defined as the date of the first PCSK9i prescription (index claim) during the enrollment window; patients were followed for ≥6 months postindex.

Prediction of Drug-Target Binding Kinetics by Comparative Binding Energy Analysis.

A growing consensus is emerging that optimizing the drug-target affinity alone under equilibrium conditions does not necessarily translate into higher potency in vivo and that instead binding kinetic parameters should be optimized to ensure better efficacy. Therefore, in silico methods are needed to predict the kinetic parameters and the mechanistic determinants of drug-protein binding. Here we demonstrate the application of COMparative BINding Energy (COMBINE) analysis to derive quantitative structure-kinetics relationships (QSKRs) for the dissociation rate constants ( ) of inhibitors of heat shock protein 90 (HSP90) and HIV-1 protease.

Management of Sleep Disturbances in Parkinson's Disease Patients, Carers and the Patient and Carer Dyadic Relationship: A Scoping Review.

Objectives: Sleep disturbances are a debilitating non-motor symptom in Parkinson's disease (PD) and negatively impact patients, their carers and the patient-carer dyadic relationship. This review outlines the phenomenology, as well as factors associated with and treatment of sleep disturbances, in PD patients and their informal carers.

Methods: The following terms were used in four databases: Parkinson*, sleep* disturbance*, carer*, dyad*, intervention* and treatment*.

A new record of Avrainvillea cf. erecta (Berkeley) A. Gepp & E. S. Gepp (Bryopsidales, Chlorophyta) from urbanized estuaries in the Hawaiian Islands.

Background: A second species in the siphonous green algal genus was recently discovered off the island of O'ahu in the Main Hawaiian Islands. Specimens were collected from Honolulu Harbor, including its entrance channel, and near Ke'ehi Harbor. These locations are both in Mālama Bay on O'ahu's south shore in or adjacent to urbanized estuaries, respectively.

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing.

Kinetoplastid parasites-trypanosomes and leishmanias-infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis.