Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

BACKGROUND: The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. METHODS: Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. RESULTS AND DISCUSSION: A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84 % of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74 % of prescribers and 84 % of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. CONCLUSION: The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines

Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: Prospective cohort study

Objective: To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (\u3c2.0 g sodium, \u3e3.5 g potassium) in adults.Design: International prospective cohort study.Setting: 18 high, middle, and low income countries, sampled from urban and rural communities.Participants: 103 570 people who provided morning fasting urine samples.Main outcome measures: Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (\u3c3 g/day), moderate (3-5 g/day), and high (\u3e5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).Results: Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of \u3c2.0 g/day of sodium and \u3e3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).Conclusions: These findings suggest that the simultaneous target of low sodium intake (\u3c2 g/day) with high potassium intake (\u3e3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events

MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated. OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation. METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB generation, DSB repair, and termination of DDRs. RESULTS: Genetic testing in a newborn with abnormal screen for severe combined immune deficiency, T-cell lymphopenia, and near absence of B cells identified a novel splice variant in MYSM1 that results in nearly absent protein expression. Radiosensitivity testing in patient\u27s peripheral blood lymphocytes showed constitutive γH2AX, a marker of DNA damage, in B cells in the absence of irradiation, suggesting a role for MYSM1 in response to DSBs generated during Ig recombination. Suppression of MYSM1 in pre-B cells did not alter generation or repair of Ig DSBs. Rather, loss of MYSM1 resulted in persistent DNA damage foci and prolonged DDR signaling. Loss of MYSM1 also led to protracted DDRs in U2OS cells with irradiation induced DSBs. CONCLUSIONS: MYSM1 regulates termination of DNA damage responses but does not function in DNA break generation and repair

Advances in Diagnosis and Management of Atypical Spinal Infections: A Comprehensive Review

Atypical spinal infections (ASIs) of the spine are a challenging pathology to management with potentially devastating morbidity and mortality. To identify patients with atypical spinal infections, it is important to recognize the often insidious clinical and radiographic presentations, in the setting of indolent and smoldering organism growth. Trending of inflammatory markers, and culturing of organisms, is essential. Once identified, the spinal infection should be treated with antibiotics and possibly various surgical interventions including decompression and possible fusion depending on spine structural integrity and stability. Early diagnosis of ASIs and immediate treatment of debilitating conditions, such as epidural abscess, correlate with fewer neurological deficits and a shorter duration of medical treatment. There have been great advances in surgical interventions and spinal fusion techniques for patients with spinal infection. Overall, ASIs remain a perplexing pathology that could be successfully treated with early diagnosis and immediate, appropriate medical, and surgical management

Clinical Outcomes with and without Adherence to Evidence-Based Medicine Guidelines for Lumbar Degenerative Spondylolisthesis Fusion Patients

Introduction: Degenerative lumbar spondylolisthesis (DS) patients are treated with instrumented fusion, following EBM guidelines, and typically have excellent clinical outcomes. However, not all lumbar fusion procedures adhere to EBM guidelines, typically due to a lack of prospective data. Objective: This retrospective study compared outcomes of DS lumbar fusion patients treated according to EBM guidelines (EBM concordant) to lumbar fused patients with procedures that did not have clear EBM literature that supported this treatment, the goal being to examine the value of present EBM to guide clinical care. Methods: A total of 125 DS patients were considered EBM concordant, while 21 patients were EBM discordant. Pre- and postsurgical ODI scores were collected. Clinical outcomes were stratified into substantial clinical benefit (SCB ΔODI \u3e10 points), minimal clinical importance benefit (MCID ΔODI ≥ 5 points), no MCID (ΔODI \u3c 5 points), and a group that showed no change or worsening ODI. Fisher\u27s exact and χ2 tests for categorical variables, Student\u27s t-test for continuous variables, and descriptive statistics were used. Statistical tests were computed at the 95% level of confidence. Results: Analysis of 125 degenerative spondylolisthesis patients was performed comparing preoperative and postoperative (6 months) ODI scores. ODI improved by 8 points in the EBM concordant group vs. 2.1 points in the EBM discordant group (p = 0.002). Compliance with EBM guidelines was associated with an odds ratio (OR) of 2.93 for achieving MCID ([CI]: 1.12-7.58, p = 0.027). Conclusions: Patients whose lumbar fusions met EBM criteria had better self-reported outcomes at six months than those who did not meet the requirements. A greater knowledge set is needed to help further support EBM-guided patient care

Factors Associated With Referring Close Contacts to an App With Individually-Tailored Vaccine Information

Background: Infants too young to be fully vaccinated are vulnerable to potentially deadly influenza and pertussis infections. The cocooning strategy limits this risk by vaccinating those likely to interact with the infant and mother during this vulnerable time, such as close friends and family members. Distribution of accurate and accessible vaccine information through existing social networks could be an important tool in increasing vaccine confidence and coverage. Methods: We surveyed 1095 pregnant women from diverse prenatal care practices in Georgia and Colorado. These women were surveyed through a mobile app to assess vaccine intentions, attitudes, beliefs, norms, and levels of trust, and then presented brief individually-tailored educational videos about maternal and infant vaccines and the cocooning strategy. They were then given the opportunity to refer up to six contacts to enroll in the app and receive similar vaccine education. Results: Twenty-eight percent of these women referred at least one contact, with an average of 2.67 contacts per referring woman. Most referrals (93%) were partners, parents, siblings, relatives, or close friends. Attitudinal constructs significantly associated with increased likelihood of referring contacts included: intention to receive maternal influenza vaccine, perceived safety of maternal Tdap vaccine, perceived efficacy of maternal influenza vaccine, perceived susceptibility to and severity of influenza during pregnancy, and trust in vaccine information from the Centers for Disease Control and Prevention (CDC) and academic institutions. Uncertainty about infant vaccine intentions was associated with decreased likelihood of referring contacts. Conclusions: Pregnant women who valued vaccination and trusted vaccine information from academic institutions were more likely to refer an educational app about vaccines than those who did not. Further research is needed to determine the potential impact of this strategy on vaccine coverage when implemented on a large scale. Trial Registration: The survey informing this article was part of a randomized controlled trial funded by the National Institutes of Health [clinicaltrials.gov registration number NCT02898688]

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Legacy of Emperor Napoleon III

Honors Program Showcas