Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association

Cats with thermal burn injuries from California wildfires show echocardiographic evidence of myocardial thickening and intracardiac thrombi.

Recent increases in the prevalence and severity of wildfires in some regions have resulted in an increased frequency of veterinary burn patients. Few studies exist regarding diagnostics and management of burn wounds in veterinary patients and current knowledge is extrapolated from human literature and research models. Post-burn cardiac injury is a common finding and predictor of mortality in human patients and echocardiography is an important tool in monitoring response to therapy and predicting outcome. We describe the notable findings from cats naturally exposed to California wildfires in 2017 and 2018. Domestic cats (n = 51) sustaining burn injuries from the Tubbs (2017) and Camp (2018) wildfires were prospectively enrolled and serial echocardiograms and cardiac troponin I evaluations were performed. Echocardiograms of affected cats revealed a high prevalence of myocardial thickening (18/51) and spontaneous echocardiographic contrast and thrombi formation (16/51). Forty-two cats survived to discharge and 6 died or were euthanized due to a possible cardiac cause. For the first time, we describe cardiovascular and coagulation effects of thermal burn and smoke inhalation in cats. Further studies in veterinary burn victims are warranted and serve as a translational research opportunity for uncovering novel disease mechanisms and therapies

Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment

PSRO update

Newsletter for Massachusetts physicians, providing updates on the development of Professional Standards Review Organizations (PSROs) as Medicare and Medicaid standards were established

PSRO update

Newsletter for Massachusetts physicians, providing updates on the development of Professional Standards Review Organizations (PSROs) as Medicare and Medicaid standards were established

Methods and Tools for Objective Assessment of Psychomotor Skills in Laparoscopic Surgery

Training and assessment paradigms for laparoscopic surgical skills are evolving from traditional mentor–trainee tutorship towards structured, more objective and safer programs. Accreditation of surgeons requires reaching a consensus on metrics and tasks used to assess surgeons’ psychomotor skills. Ongoing development of tracking systems and software solutions has allowed for the expansion of novel training and assessment means in laparoscopy. The current challenge is to adapt and include these systems within training programs, and to exploit their possibilities for evaluation purposes. This paper describes the state of the art in research on measuring and assessing psychomotor laparoscopic skills. It gives an overview on tracking systems as well as on metrics and advanced statistical and machine learning techniques employed for evaluation purposes. The later ones have a potential to be used as an aid in deciding on the surgical competence level, which is an important aspect when accreditation of the surgeons in particular, and patient safety in general, are considered. The prospective of these methods and tools make them complementary means for surgical assessment of motor skills, especially in the early stages of training. Successful examples such as the Fundamentals of Laparoscopic Surgery should help drive a paradigm change to structured curricula based on objective parameters. These may improve the accreditation of new surgeons, as well as optimize their already overloaded training schedules

Projections of the healthcare costs and disease burden due to hepatitis C infection under different treatment policies in Malaysia, 2018-2040

The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis

Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = –2.0, P \u3c .05, r = –.48, as did tic-related impairment, z = –2.4, P \u3c .05, r = –.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol