Substantial progress has been made in implementing routine infant hepatitis B vaccination in the United States. However, in 1996, an estimated 65 000 acute hepatitis B cases occurred, the majority of ...which were among young adults in high-risk groups. Recent surveys have found very low vaccination coverage among several high-risk groups, including men who have sex with men and patients with sexually transmitted diseases (STDs). Targeted vaccination of persons with risk factors for hepatitis B virus (HBV) infection can be provided in a variety of settings including family planning clinics, STD clinics, drug treatment centres, detention centres, jails and prisons. However, vaccination programmes have been infrequently implemented in these settings and the majority of persons with acute hepatitis B cases have had a missed opportunity for vaccination in the past. Thus, in order to accelerate elimination of HBV transmission in the United States, increased efforts are needed to implement effective hepatitis B vaccination programmes targeted to adolescents and adults in high-risk groups.
A percentage tissue altered (PTA) score of ≥40% has been advocated as an independent indicator of post-operative ectasia risk following laser in-situ keratomileusis (LASIK). This study was performed ...to test the hypothesis that refractive procedures, such as laser-assisted sub-epithelial keratectomy (LASEK) or small incision lenticule extraction (SMILE), may alter the range of PTA, within which refractive corneal surgery can be safely performed.
Refractive department, tertiary ophthalmic hospital.
Retrospective observational study.
Review of case notes was performed for patients who presented for refractive surgeries, other than LASIK. To determine the risk of corneal ectasia for each patient prior to refractive surgery, we estimated what each patient's PTA would have been if they had undergone LASIK. The Randleman Ectasia Risk Score System (ERSS) was also calculated.
114 eyes (66 patients) were included. 94 eyes underwent SMILE. 20 eyes underwent LASEK. A significant proportion of eyes had PTA ≥40% - SMILE eyes: up to 31.9%, LASEK eyes: up to 60.0% (at presumed LASIK flap of 120 μm). The maximum calculated PTA was up to 47.9% in the SMILE group and up to 51.5% in the LASEK group. Using ERSS, 12.8-16% of SMILE eyes and 15.0-80.0% of LASEK eyes would have been considered to have moderate-to-high ectasia risk. No post-surgical ectasia was observed at 3 years.
SMILE and LASEK alter the range of PTA, within which corneal refractive surgery may be performed with a lower risk of developing post-operative corneal ectasia; a safe PTA threshold needs to be determined for these procedures before recommendations for clinical practice can be made.
Zidovudine (ZDV) requires intracellular phosphorylation to ZDV triphosphate (ZDV-TP) prior to the inhibition of HIV replication. The effect of ZDV dose on the formation of intracellular ...phosphorylated metabolites may help define the optimum daily dose of ZDV, which is still unknown.
The plasma and intracellular phosphorylated metabolite concentrations of ZDV were determined over a 12 h period following oral administration of 100 and 300 mg ZDV to 10 HIV-seropositive patients at steady state during two dosing regimens (i.e., 100 mg three times daily and 300 mg twice daily). The intracellular ZDV phosphates, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV-TP were measured in peripheral blood mononuclear cells using a combination of high-performance liquid chromatography and radioimmunoassay.
There was a greater than threefold increase in maximum plasma concentration (Cmax) following 300 mg ZDV when compared with 100 mg ZDV (mean +/- SD, 2.59 +/- 0.52 versus 0.70 +/- 0.14 mumol/l). The area under the concentration time curve (AUC0-12 h) was also significantly increased (4.59 +/- 0.79 versus 1.42 +/- 0.51 mumol/l x h) following 300 mg ZDV dose. For total intracellular ZDV phosphate metabolites the AUC0-12 h was doubled (7.64 +/- 3.67 versus 3.71 +/- 1.83 pmol/10(6) cells x h) in patients taking 300 mg ZDV compared with 100 mg. The AUC0-12 h for ZDV-MP was significantly increased at the higher dose (6.47 +/- 3.14 versus 2.77 +/- 1.70 pmol/10(6) cells x h), whereas the active moiety ZDV-TP was variable and not significantly different (0.42 +/- 0.42 versus 0.61 +/- 0.81 pmol/10(6) cells x h) following 100 and 300 mg ZDV.
Administration of 100 mg ZDV orally produces significantly less of the potentially toxic metabolite, ZDV-MP, and comparative, although variable, concentrations of the active metabolite ZDV-TP when compared with 300 mg ZDV orally. This finding supports clinical data indicating the efficacy of low-dose (300 mg daily) ZDV. The measurement of intracellular phosphorylated metabolites advances our understanding of the clinical pharmacology of ZDV.
We report a child of 3 years 9 months with the Marshall-Smith syndrome (MSS), characterised by the typical facial features, developmental delay, and advanced bone age. After the diagnosis was made at ...5 months of age, careful observation for respiratory complications and failure to thrive was initiated. By 3 1/2 years of age, although our patient had no life threatening respiratory complications, investigation showed significant upper airway obstruction, which has been successfully treated. Aggressive treatment for failure to thrive has also allowed her to maintain a weight on the 50th centile. The purpose of this report is to suggest that early diagnosis and aggressive management may improve the ultimate prognosis with respect to the respiratory and feeding difficulties seen in this rare syndrome.
AIDS, caused by human immunodeficiency virus (HIV), is one of the world's most serious health problems, with current protocols being inadequate for either prevention or successful long-term ...treatment. In retroviruses such as HIV, the enzyme reverse transcriptase copies the single-stranded RNA genome into double-stranded DNA that is then integrated into the chromosomes of infected cells. Reverse transcriptase is the target of the most widely used treatments for AIDS, 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), but resistant strains of HIV-1 arise in patients after a relatively short time. There are several nonnucleoside inhibitors of HIV-1 reverse transcriptase, but resistance to such agents also develops rapidly. We report here the structure at 7 A resolution of a ternary complex of the HIV-1 reverse transcriptase heterodimer, a monoclonal antibody Fab fragment, and a duplex DNA template-primer. The double-stranded DNA binds in a groove on the surface of the enzyme. The electron density near one end of the DNA matches well with the known structure of the HIV-1 reverse transcriptase RNase H domain. At the opposite end of the DNA, a mercurated derivative of UTP has been localized by difference Fourier methods, allowing tentative identification of the polymerase nucleoside triphosphate binding site. We also determined the structure of the reverse transcriptase/Fab complex in the absence of template-primer to compare the bound and free forms of the enzyme. The presence of DNA correlates with movement of protein electron density in the vicinity of the putative template-primer binding groove. These results have important implications for developing improved inhibitors of reverse transcriptase for the treatment of AIDS.
The exercise psychology literature includes an intriguing, albeit not frequently discussed, paradox by juxtaposing two conclusions: (a) that exercise makes most people feel better and (b) that most ...people are physically inactive or inadequately active. In this article, we propose that this might be an artifact rather than a paradox. Specifically, we question the generality of the conclusion that exercise makes people feel better by proposing that (a) occasional findings of negative affective changes tend to be discounted, (b) potentially relevant negative affective states are not always measured, (c) examining changes from pre- to postexercise could miss negative changes during exercise, and (d) analyzing changes only at the level of group aggregates might conceal divergent patterns at the level of individuals or subgroups. Data from a study of 12 men participating in a 90-min walk-run protocol designed to simulate the demands of sports games (e.g., soccer) are used to illustrate these points.
Background
In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is ...a need to support the transformation of the health care system into integrated care with organizational health literacy.
Main body
As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real‐life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self‐care through technology‐assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next‐generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real‐world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally‐enabled, integrated, person‐centred care.
Conclusion
In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
The goal of this study was to determine whether depressive symptoms predict type 2 diabetes.
We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of ...hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48-67 years, who were subsequently followed for 6 years for the development of type 2 diabetes.
At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard RH 1.63, 95% CI 1.31-2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02-1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10-1.73).
In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.
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