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1.
J Evol Biol ; 37(4): 442-450, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38456649

ABSTRACT

Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation between life span and the proportion of time cybrids spent moving while alive. Our results suggest that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.


Subject(s)
Drosophila melanogaster , Mitochondria , Animals , Female , Drosophila melanogaster/physiology , Mitochondria/genetics , Longevity/genetics , Genotype , Fertility/genetics
2.
Am J Cardiovasc Drugs ; 22(6): 615-631, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35570249

ABSTRACT

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).


Subject(s)
Atrial Fibrillation , Stroke , Venous Thromboembolism , Humans , Venous Thromboembolism/drug therapy , Pyridones/adverse effects , Warfarin/therapeutic use , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Obesity/complications , Obesity/drug therapy , Stroke/epidemiology , Administration, Oral , Observational Studies as Topic
3.
Stem Cells Transl Med ; 10(8): 1170-1183, 2021 08.
Article in English | MEDLINE | ID: mdl-33794062

ABSTRACT

Craniofacial bones protect vital organs, perform important physiological functions, and shape facial identity. Critical-size defects (CSDs) in calvarial bones, which will not heal spontaneously, are caused by trauma, congenital defects, or tumor resections. They pose a great challenge for patients and physicians, and significantly compromise quality of life. Currently, calvarial CSDs are treated either by allogenic or autologous grafts, metal or other synthetic plates that are associated with considerable complications. While previous studies have explored tissue regeneration for calvarial defects, most have been done in small animal models with limited translational value. Here we define a swine calvarial CSD model and show a novel approach to regenerate high-quality bone in these defects by combining mesenchymal stem cells (MSCs) with a three-dimensional (3D)-printed osteoconductive HA/TCP scaffold. Specifically, we have compared the performance of dental pulp neural crest MSCs (DPNCCs) to bone marrow aspirate (BMA) combined with a 3D-printed HA/TCP scaffold to regenerate bone in a calvarial CSD (>7.0 cm2 ). Both DPNCCs and BMA loaded onto the 3D-printed osteoconductive scaffold support the regeneration of calvarial bone with density, compression strength, and trabecular structures similar to native bone. Our study demonstrates a novel application of an original scaffold design combined with DPNCCs or BMA to support regeneration of high-quality bone in a newly defined and clinically relevant swine calvarial CSD model. This discovery may have important impact on bone regeneration beyond the craniofacial region and will ultimately benefit patients who suffer from debilitating CSDs.


Subject(s)
Mesenchymal Stem Cells , Tissue Scaffolds , Animals , Bone Regeneration , Humans , Osteogenesis , Quality of Life , Skull/surgery , Swine , Tissue Scaffolds/chemistry
4.
Lancet Public Health ; 6(5): e300-e308, 2021 05.
Article in English | MEDLINE | ID: mdl-33765455

ABSTRACT

BACKGROUND: Prisons are recognised as high-risk environments for tuberculosis, but there has been little systematic investigation of the global and regional incidence and prevalence of tuberculosis, and its determinants, in prisons. We did a systematic review and meta-analysis to assess the incidence and prevalence of tuberculosis in incarcerated populations by geographical region. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Knowledge, and the LILACS electronic database from Jan 1, 1980, to Nov 15, 2020, for cross-sectional and cohort studies reporting the incidence of Mycobacterium tuberculosis infection, incidence of tuberculosis, or prevalence of tuberculosis among incarcerated individuals in all geographical regions. We extracted data from individual studies, and calculated pooled estimates of incidence and prevalence through hierarchical Bayesian meta-regression modelling. We also did subgroup analyses by region. Incidence rate ratios between prisons and the general population were calculated by dividing the incidence of tuberculosis in prisons by WHO estimates of the national population-level incidence. FINDINGS: We identified 159 relevant studies; 11 investigated the incidence of M tuberculosis infection (n=16 318), 51 investigated the incidence of tuberculosis (n=1 858 323), and 106 investigated the prevalence of tuberculosis (n=6 727 513) in incarcerated populations. The overall pooled incidence of M tuberculosis infection among prisoners was 15·0 (95% credible interval [CrI] 3·8-41·6) per 100 person-years. The incidence of tuberculosis (per 100 000 person-years) among prisoners was highest in studies from the WHO African (2190 [95% CrI 810-4840] cases) and South-East Asia (1550 [240-5300] cases) regions and in South America (970 [460-1860] cases), and lowest in North America (30 [20-50] cases) and the WHO Eastern Mediterranean region (270 [50-880] cases). The prevalence of tuberculosis was greater than 1000 per 100 000 prisoners in all global regions except for North America and the Western Pacific, and highest in the WHO South-East Asia region (1810 [95% CrI 670-4000] cases per 100 000 prisoners). The incidence rate ratio between prisons and the general population was much higher in South America (26·9; 95% CrI 17·1-40·1) than in other regions, but was nevertheless higher than ten in the WHO African (12·6; 6·2-22·3), Eastern Mediterranean (15·6; 6·5-32·5), and South-East Asia (11·7; 4·1-27·1) regions. INTERPRETATION: Globally, people in prison are at high risk of contracting M tuberculosis infection and developing tuberculosis, with consistent disparities between prisons and the general population across regions. Tuberculosis control programmes should prioritise preventive interventions among incarcerated populations. FUNDING: US National Institutes of Health.


Subject(s)
Global Health/statistics & numerical data , Prisoners/statistics & numerical data , Tuberculosis/epidemiology , Humans , Incidence , Prevalence
5.
Invest Ophthalmol Vis Sci ; 61(10): 16, 2020 08 03.
Article in English | MEDLINE | ID: mdl-32766747

ABSTRACT

Purpose: To evaluate the short-term changes in inner retinal function using the photopic negative response (PhNR) after intraocular pressure (IOP) reduction in glaucoma. Methods: Forty-seven participants with glaucoma who were commencing a new or additional IOP-lowering therapy (treatment group) and 39 participants with stable glaucoma (control group) were recruited. IOP, visual field, retinal nerve fiber layer thickness, and electroretinograms (ERGs) were recorded at baseline and at a follow-up visit (3 ± 2 months). An optimized protocol developed for a portable ERG device was used to record the PhNR. The PhNR saturated amplitude (Vmax), Vmax ratio, semi-saturation constant (K), and slope of the Naka-Rushton function were analyzed. Results: A significant percentage reduction in IOP was observed in the treatment group (28 ± 3%) compared to the control group (2 ± 3%; P < 0.0001). For PhNR Vmax, there was no significant interaction (F1,83 = 2.099, P = 0.15), but there was a significant difference between the two time points (F1,83 = 5.689, P = 0.019). Post hoc analysis showed a significant difference between baseline and 3 months in the treatment group (mean difference, 1.23 µV; 95% confidence interval [CI], 0.24-2.22) but not in the control group (0.30 µV; 95% CI, 0.78-1.38). K and slope were not significantly different in either group. Improvement beyond test-retest variability was seen in 17% of participants in the treatment group compared to 3% in the control group (P = 0.007, χ2 test). Conclusions: The optimized protocol for measuring the PhNR detected short-term improvements in a proportion of participants following IOP reduction, although the majority showed no change.


Subject(s)
Antihypertensive Agents/therapeutic use , Glaucoma/drug therapy , Intraocular Pressure/drug effects , Retina/physiopathology , Aged , Aged, 80 and over , Color Vision/physiology , Electroretinography , Female , Glaucoma/physiopathology , Humans , Male , Middle Aged , Nerve Fibers/pathology , Photic Stimulation , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence , Tonometry, Ocular , Trabeculectomy , Visual Field Tests , Visual Fields/physiology
6.
J Glaucoma ; 29(3): 175-183, 2020 03.
Article in English | MEDLINE | ID: mdl-31790066

ABSTRACT

PRECIS: As new glaucoma treatments arise, including minimally invasive glaucoma surgeries and new classes of glaucoma medications, it is important to examine the prescription trends of current topical glaucoma medications and how they may change. PURPOSE: To determine the prescribing trends of topical glaucoma medications in Australia from 2001 to 2017. METHODS AND ANALYSIS: Pharmaceutical Benefits Scheme (PBS) item numbers were used to determine glaucoma medication prescribing rates from 2001 to 2017. All data were adjusted for population (/100,000) as per the Australian Bureau of Statistics (ABS) population data. RESULTS: Overall prescription rates for glaucoma medications ranged between 67,904 and 86,936 per 100,000 from 2001 to 2017. An upward trend was noted from 2001 to 2015, with the exception of a notable decline in 2013 by 14.7%, before then increasing by 13.7% in 2014. After 2015, prescribing rates were seen to decrease over the subsequent years in the study period. Latanoprost remained the most prescribed medication and prostaglandin the most prescribed class. Prescribing rates of single-agent beta-blockers were noted to decrease during the 17-year period, particularly with the introduction of combination agents, which note an upward trend. Brinzolamide/brimonidine has increased by 50.0% from 2016 to 2017. CONCLUSIONS: Total rates of prescriptions have remained relatively stable from 2001 to 2017. The number of medications prescribed when considering combination agents separately was seen to be increasing from 2001 to 2015. From 2015 to 2017, a downward trend was noted in the number of medications prescribed. Prostaglandins remain the most prescribed class throughout the study period.


Subject(s)
Antihypertensive Agents/administration & dosage , Drug Prescriptions/statistics & numerical data , Glaucoma, Open-Angle/drug therapy , Intraocular Pressure/drug effects , Practice Patterns, Physicians'/trends , Administration, Ophthalmic , Adrenergic Agonists/administration & dosage , Australia , Brimonidine Tartrate/administration & dosage , Carbonic Anhydrase Inhibitors/administration & dosage , Drug Therapy, Combination , Drug Utilization/trends , Health Services Research , Health Surveys , Humans , Ophthalmic Solutions , Sulfonamides/administration & dosage , Thiazines/administration & dosage , Timolol/administration & dosage
7.
Clin Exp Optom ; 100(4): 365-368, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27998001

ABSTRACT

BACKGROUND: Non-penetrating ocular injuries from badminton shuttlecocks can result in severe damage and life-long complications. This case series highlights the morbidity of such injuries, particularly in regard to post-traumatic glaucoma. METHODS: This is a retrospective case series of 12 patients with shuttlecock-related blunt eye injuries sustained during badminton play without eye protection. By approaching colleagues through conference presentations and networking, the authors have attempted to gather all known cases of shuttlecock ocular injury managed in tertiary ocular emergency departments or private ophthalmological clinics in Victoria and New South Wales, Australia in 2015. RESULTS: This is the first multicentre case series to describe badminton-related ocular injuries in Australia. Our case series demonstrates, in particular, long-term glaucoma-related morbidity for patients over a large age range (16 to 77 years), with one patient requiring ongoing management 26 years following their initial injury. The cases reported further add to the literature promoting awareness of badminton-related ocular injury. CONCLUSIONS: We encourage player education and advocacy on badminton-related eye injuries and appropriate use of eye protection to reduce associated morbidity.


Subject(s)
Athletic Injuries/complications , Eye Injuries/complications , Eye Protective Devices/statistics & numerical data , Glaucoma/etiology , Racquet Sports/injuries , Wounds, Nonpenetrating/complications , Adolescent , Adult , Aged , Athletic Injuries/prevention & control , Eye Injuries/prevention & control , Female , Glaucoma/epidemiology , Humans , Male , Middle Aged , Morbidity/trends , New South Wales/epidemiology , Retrospective Studies , Victoria/epidemiology , Visual Acuity , Wounds, Nonpenetrating/prevention & control , Young Adult
9.
Ther Innov Regul Sci ; 48(3): 347-356, 2014 May.
Article in English | MEDLINE | ID: mdl-30235543

ABSTRACT

Survey methods were used to explore the expectations and recommendations of senior business development professionals with respect to the roles, activities, and interactions with US universities in the development of new medical products. This target group was chosen because it was judged to be most likely to interact with university faculty and technology transfer services and seek and acquire university assets. The survey instrument was first reviewed by a focus group of individuals with experience both in technology transfer and in academic or industry policy, then distributed to a selected subset of 80 business development professionals, of whom 72 responded. Serious concerns were expressed over the current mechanisms for technology transfer and university support of commercialization. When asked if they believed that there is a need for a change in the way that universities interact with industry in the US, 86% of the respondents replied that they either strongly agreed or agreed that there was, indeed, a need for change. Among several areas that might be improved, the availability of proof-of-concept facilities and funds for early-stage feasibility studies were most often identified as important.

10.
IEEE Trans Pattern Anal Mach Intell ; 32(1): 148-64, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19926905

ABSTRACT

Given an unstructured collection of captioned images of cluttered scenes featuring a variety of objects, our goal is to simultaneously learn the names and appearances of the objects. Only a small fraction of local features within any given image are associated with a particular caption word, and captions may contain irrelevant words not associated with any image object. We propose a novel algorithm that uses the repetition of feature neighborhoods across training images and a measure of correspondence with caption words to learn meaningful feature configurations (representing named objects). We also introduce a graph-based appearance model that captures some of the structure of an object by encoding the spatial relationships among the local visual features. In an iterative procedure, we use language (the words) to drive a perceptual grouping process that assembles an appearance model for a named object. Results of applying our method to three data sets in a variety of conditions demonstrate that, from complex, cluttered, real-world scenes with noisy captions, we can learn both the names and appearances of objects, resulting in a set of models invariant to translation, scale, orientation, occlusion, and minor changes in viewpoint or articulation. These named models, in turn, are used to automatically annotate new, uncaptioned images, thereby facilitating keyword-based image retrieval.

11.
Am J Emerg Med ; 28(1): 119.e1-3, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20006233

ABSTRACT

The authors report 2 patients who experienced medial wall blowout fractures. Both patients presented with significant restriction of upgaze, mild proptosis, and crepitus of the upper lid. Computed tomography revealed significant pneumo-orbita filling the superior orbit with inferior displacement of the muscle cone and subcutaneous emphysema. No floor fractures were seen in either patient, but in both cases, the medial wall was breached and was almost certainly the source of the intraorbital air. Patients were managed conservatively, and the vertical gaze deficiencies resolved after 3 to 5 days. Large amounts of intraorbital and extraorbital air in the absence of a floor fracture can imitate inferior rectus entrapment and could potentially lead to unnecessary surgical intervention.


Subject(s)
Eye Diseases/diagnosis , Orbit/injuries , Orbital Fractures/diagnosis , Adult , Diagnosis, Differential , Female , Head Injuries, Closed/complications , Humans , Male , Oculomotor Muscles , Orbit/diagnostic imaging , Orbital Fractures/diagnostic imaging , Orbital Fractures/etiology , Subcutaneous Emphysema/diagnostic imaging , Subcutaneous Emphysema/etiology , Tomography, X-Ray Computed , Young Adult
12.
J Clin Hypertens (Greenwich) ; 11(10): 585-93, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19817942

ABSTRACT

African Americans with diabetes +/- the metabolic syndrome are at high risk for cardiovascular disease. This subanalysis of the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE) trial studied attainment of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) goals by 8 flexibly titrated doses (5/10-10/80 mg) of amlodipine/atorvastatin single pill in 494 African Americans with hypertension and dyslipidemia, according to the presence of diabetes +/- the metabolic syndrome. In 169 diabetic patients, the metabolic syndrome was associated with poorer BP goal attainment (38.5% vs 48.5% in diabetic patients without the metabolic syndrome). Among diabetic patients (+/- the metabolic syndrome) 61% to 62% reached LDL-C goal. More than 60% of patients with diabetes uncontrolled for LDL-C were maintained on suboptimal atorvastatin therapy (mean final dose: 29.9 mg vs maximum of 80 mg). Reluctance to intensify therapy to attain accepted targets in high-risk individuals suggests a degree of clinical inertia not explained by objective evidence of dose-dependent intolerance.


Subject(s)
Amlodipine/therapeutic use , Anticholesteremic Agents/therapeutic use , Black or African American , Diabetes Mellitus, Type 2/physiopathology , Heptanoic Acids/therapeutic use , Hypercholesterolemia/drug therapy , Hypertension/drug therapy , Metabolic Syndrome/physiopathology , Pyrroles/therapeutic use , Adult , Black or African American/ethnology , Aged , Amlodipine/administration & dosage , Amlodipine/adverse effects , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/adverse effects , Atorvastatin , Blood Pressure/physiology , Diabetes Mellitus, Type 2/ethnology , Dose-Response Relationship, Drug , Drug Combinations , Drug Tolerance , Female , Heptanoic Acids/administration & dosage , Heptanoic Acids/adverse effects , Humans , Hypercholesterolemia/blood , Hypertension/physiopathology , Lipids/blood , Male , Metabolic Syndrome/ethnology , Middle Aged , Pyrroles/administration & dosage , Pyrroles/adverse effects , Retrospective Studies , Treatment Outcome
13.
Mayo Clin Proc ; 83(1): 35-45, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18174006

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of single-pill amlodipine/atorvastatin therapy for the simultaneous treatment of hypertension (HTN) and dyslipidemia in African Americans. PATIENTS AND METHODS: Conducted between July 19, 2004, and August 9, 2005, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points trial was a 20-week, open-label, noncomparative, multicenter trial of the efficacy and safety of single-pill amlodipine/atorvastatin in controlling elevated blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in African Americans with concomitant HTN and dyslipidemia and either no additional risk factors, 1 or more cardiovascular risk factors, or coronary heart disease or a risk equivalent. Eight dosage strengths of single-pill amlodipine/atorvastatin were flexibly titrated. The primary efficacy assessment of the main trial was the percentage of patients who attained the LDL-C treatment goals of both the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National Cholesterol Education Program Adult Treatment Panel III. RESULTS: Of the 1170 African American patients screened, 501 were enrolled in the study and 499 received drug therapy. At end point, 236 (48.3%) of 489 patients reached both their BP and LDLC goals (vs 4 [0.8%] of 484 at baseline); 280 (56.8%) of 493 reached BP goals (vs 7 [1.4%] of 494 at baseline); and 361 (73.7%) of 490 reached LDL-C goals (vs 138 [28.5%] of 484 at baseline). Among the 499 patients receiving drug therapy, common treatment-related adverse events were peripheral edema (17 patients [3.4%]), headache (11 [2.2%]), myalgia (11 [2.2%]), and constipation (10 [2.0%]). CONCLUSION: Single-pill amlodipine/atorvastatin therapy was well tolerated and effectively targeted HTN and dyslipidemia in this population of African Americans who were at risk of cardiovascular disease.


Subject(s)
Amlodipine/administration & dosage , Anticholesteremic Agents/administration & dosage , Antihypertensive Agents/administration & dosage , Black or African American , Heptanoic Acids/administration & dosage , Hypercholesterolemia/drug therapy , Hypertension/drug therapy , Pyrroles/administration & dosage , Adult , Aged , Atorvastatin , Drug Combinations , Female , Follow-Up Studies , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/ethnology , Hypertension/complications , Hypertension/ethnology , Male , Middle Aged , Treatment Outcome
14.
Curr Pharm Des ; 13(10): 1069-76, 2007.
Article in English | MEDLINE | ID: mdl-17430169

ABSTRACT

Risk factors for atherosclerotic cardiovascular disease (CVD) are highly co-prevalent but poorly identified and treated. The Screening for Heart Attack Prevention and Education (SHAPE) Task Force from the Association for Eradication of Heart Attack (AEHA) has recently proposed a new strategy that recommends screening for subclinical atherosclerosis and implementing aggressive treatment of "vulnerable patients". The Task Force has also envisioned future developments that may shift mass screening strategies to mass prophylactic therapy. The "Polypill" concept, introduced by Wald and Law suggests a combination of statin, low-dose antihypertensives, aspirin and folic acid, in a single pill, taken prophylactically by high risk population can cut CVD event rates by as much as 80%. In this communication, we review the challenges and promises of such a strategy. "Polypill" is but one of an astronomical number of possible multiconstituent pills (MCCP). Attractive as the MCCP concept is, it lacks evidence from randomized controlled trials, and begs numerous questions about the credibility of the concept, the design and synthesis of such complex pills, pharmacokinetics, pharmacodynamics, bioequivalence, "class" vs. unique properties, interactions, evidence of clinical efficacy and safety, regulatory approval, post-marketing surveillance, prescription vs. over-the-counter use, responsibility for initiating and monitoring therapy, patient education, counterfeiting and importation, reimbursement, advertisement, patent protection, commercial viability, etc. If these issues are favorably addressed, MCCP stand to dramatically change the manner in which CVD is prevented particularly in developing societies. Notwithstanding, assuming low commercial interests, realizing the promises of MCCP will demand serious attention from national public health policymakers. The clinical and regulatory implications of population-based secondary prevention (which rely on a different evidence base, and in which entirely different risk-benefit and cost-effectiveness considerations apply) remain issues for active debate.


Subject(s)
Atherosclerosis/drug therapy , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Antihypertensive Agents/therapeutic use , Aspirin/therapeutic use , Atherosclerosis/complications , Cardiovascular Agents/adverse effects , Cardiovascular Diseases/etiology , Drug Combinations , Drug Therapy/trends , Folic Acid/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Primary Prevention/trends , Vitamin B Complex/therapeutic use
15.
Am J Cardiol ; 99(5): 632-5, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17317362

ABSTRACT

After acute coronary syndromes (ACSs), older patients are particularly susceptible to early complications, including death and recurrent ACS. Lipid management guidelines do not differentiate elderly from younger patients, and lack of evidence for statin benefits in older patients has led to underutilization of statins in the elderly. The MIRACL study randomized 3,086 patients to 16 weeks of 80 mg/day of atorvastatin or placebo 24 to 96 hours after ACS and demonstrated significant decreases in the combined primary end point (nonfatal acute myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia). This post hoc analysis compared benefits of 80 mg of atorvastatin in older (> or =65 years) versus younger (<65 years) patients. Event rates were approximately two- to threefold higher in older than in younger patients. Treatment-by-age heterogeneity testing indicated no difference in treatment effect by age for any of the primary or secondary end points, and relative risk decreases in the primary end point with atorvastatin versus placebo were similar in younger and older patients (22% vs 14%, respectively). The safety profile of atorvastatin was similar between the 2 age groups. In conclusion, these results and a greater immediate cardiovascular risk in older patients argue for early, intensive atorvastatin therapy as routine practice after ACS.


Subject(s)
Age Factors , Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Myocardial Ischemia/prevention & control , Pyrroles/administration & dosage , Aged , Aged, 80 and over , Atorvastatin , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Retrospective Studies , Syndrome , Treatment Outcome
16.
Faraday Discuss ; 133: 43-50; discussion 83-102, 449-52, 2006.
Article in English | MEDLINE | ID: mdl-17191441

ABSTRACT

We investigate the contribution made by Raman scattering to the formation of molecular hydrogen in astrophysical environments characteristic of the early stages of the evolution of the universe. In the Raman process that we study, a photon is scattered by a pair of colliding hydrogen atoms leaving a hydrogen molecule that is stabilized by the transfer of kinetic and binding energy to the photon. We use a formulation for calculating the photon scattering cross section in which an infinite sum of matrix elements over rovibrational levels of dipole accessible electronic states is replaced by a single matrix element of a Green's function. We evaluate this matrix element by using a discrete variable representation.

17.
Am J Cardiol ; 98(2A): 2H-15H, 2006 Jul 17.
Article in English | MEDLINE | ID: mdl-16843744

ABSTRACT

Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.


Subject(s)
Coronary Artery Disease/prevention & control , Patient Education as Topic , Coronary Artery Disease/etiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Disease Progression , Humans , Mass Screening , Practice Guidelines as Topic , Risk Assessment
19.
Cancer Epidemiol Biomarkers Prev ; 13(3): 391-7, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15006914

ABSTRACT

The essential micronutrient, selenium, is at low levels in the New Zealand diet. Selenium is a component of a number of proteins involved in the maintenance of genomic stability, and recommended daily allowances (RDA) are set on saturation levels for glutathione peroxidase (GPx), a key enzyme in surveillance against oxidative stress. It has been assumed but not proven that this level will be adequate for other key selenoenzymes. The "Negative Biopsy Trial" identifies a group of New Zealand individuals at high risk of prostate cancer, whose serum selenium levels will be monitored and who will be supplemented with a yeast-based tablet, with or without selenium, over an extended time. Access to patients on this trial provides the opportunity to ask the more generic question as to whether selenium levels in this population are adequate to maintain genomic stability. The single cell gel electrophoresis (comet) assay was used to study DNA damage in blood leukocytes harvested from these volunteers. Average serum selenium levels before randomization was 97.8 +/- 16.6 ng/ml, low by international standards. For the half of the population below this mean value, lower serum selenium levels showed a statistically significant inverse relationship (P = 0.02) with overall accumulated DNA damage. Although other interpretations cannot be excluded, the data suggest that the selenium intake in half of this population is marginal for adequate repair of DNA damage, increasing susceptibility to cancer and other degenerative diseases. It also raises the question as to whether glutathione peroxidase saturation levels are appropriate indicators of the optimal selenium levels for a given population.


Subject(s)
DNA Damage , DNA Repair , Dietary Supplements , Prostatic Neoplasms/etiology , Prostatic Neoplasms/genetics , Selenium/blood , Selenium/pharmacology , Aged , Biomarkers, Tumor/analysis , Cohort Studies , Comet Assay , Diet , Glutathione Peroxidase/analysis , Humans , Leukocytes , Male , Middle Aged , Risk Factors
20.
J Occup Rehabil ; 13(2): 79-89, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12708102

ABSTRACT

STUDY DESIGN: A cross-sectional analytic study was conducted. OBJECTIVES: To collect normative data on back extensor endurance holding times and evaluate the discriminative validity of the Biering-Sorensen test in a group of coal miners in Australia. SUMMARY OF BACKGROUND DATA: Low back pain is a common complaint among those working in the Australian coal mining industry. One test that may be predictive of first-time episodes of low back pain is the Biering-Sorensen test of back extensor endurance strength. While this test has been evaluated in overseas sedentary populations, normative data and the discriminative ability of the test have not been evaluated with coal miners. METHODS: Eighty-eight coal miners completed a questionnaire for known risk factors for low back pain, performed the Biering-Sorensen test, and undertook a test of aerobic fitness. Data analysis was performed to describe the groups and to determine whether any significant difference existed between those with a past history of low back pain and those without. RESULTS: Significantly lower than expected holding times were found in this group of coal miners (mean 113 s). This result was significantly lower than demonstrated in previous studies (mean 138 s, t87 = 6.32, p < 0.001). When holding times for those with a past history of low back pain were compared with times for those with no history of low back pain, the difference was not statistically significant (t86 = 1.56, p = 0.12), nor was there a significant difference in fitness between those with a past history of low back pain and those without (t86 = 0.47, p = 0.64). DISCUSSION/CONCLUSIONS: Coal miners in Australia have lower than normal Biering-Sorensen holding times. This lower back holding time does not differ between coal miners with a past history of low back pain and those without.


Subject(s)
Coal Mining , Exercise Test/methods , Low Back Pain/diagnosis , Muscle, Skeletal/physiology , Occupational Diseases/diagnosis , Adult , Australia , Back , Cross-Sectional Studies , Humans , Male , Middle Aged , Physical Endurance/physiology , Predictive Value of Tests
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