Andrew Schamess's Public Library

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"Background

Drugs for neuropathic pain have incomplete efficacy and dose-limiting side-effects when given as monotherapy. We assessed the efficacy and tolerability of combined nortriptyline and gabapentin compared with each drug given alone.
Methods

In this double-blind, double-dummy, crossover trial, patients with diabetic polyneuropathy or postherpetic neuralgia, and who had a daily pain score of at least 4 (scale 0–10), were enrolled and treated at one study site in Canada between Nov 5, 2004, and Dec 13, 2007. 56 patients were randomised in a 1:1:1 ratio with a balanced Latin square design to receive one of three sequences of daily oral gabapentin, nortriptyline, and their combination. In sequence, a different drug was given to each randomised group in three treatment periods. During each 6-week treatment period, drug doses were titrated towards maximum tolerated dose. The primary outcome was mean daily pain at maximum tolerated dose. Analysis was by intention to treat. This trial is registered, number ISRCTN73178636.
Findings

45 patients completed all three treatment periods; 47 patients completed at least two treatment periods and were analysed for the primary outcome. Mean daily pain (0–10; numerical rating scale) was 5·4 (95% CI 5·0 to 5·8) at baseline, and at maximum tolerated dose, pain was 3·2 (2·5 to 3·8) for gabapentin, 2·9 (2·4 to 3·4) for nortriptyline, and 2·3 (1·8 to 2·8) for combination treatment. Pain with combination treatment was significantly lower than with gabapentin (−0·9, 95% CI −1·4 to −0·3, p=0·001) or nortriptyline alone (−0·6, 95% CI −1·1 to −0·1, p=0·02). At maximum tolerated dose, the most common adverse event was dry mouth, which was significantly less frequent in patients on gabapentin than on nortriptyline (p<0·0001) or combination treatment (p<0·0001). No serious adverse events were recorded for any patients during the trial.
Interpretation

Combined gabapentin and nortriptyline seems to be more efficacious than either drug given alone for neuropathic pain, therefore we reco

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medicine journals pain management neurology diabetes post-herpetic neuralgia

"A large, widening gap exists between the incomes of primary care physicians and those of many specialists. This disparity is important because noncompetitive primary care incomes discourage medical school graduates from choosing primary care careers.

The Resource-Based Relative Value Scale, designed to reduce the inequality between fees for office visits and payment for procedures, failed to prevent the widening primary care–specialty income gap for 4 reasons: 1) The volume of diagnostic and imaging procedures has increased far more rapidly than the volume of office visits, which benefits specialists who perform those procedures; 2) the process of updating fees every 5 years is heavily influenced by the Relative Value Scale Update Committee, which is composed mainly of specialists; 3) Medicare's formula for controlling physician payments penalizes primary care physicians; and 4) private insurers tend to pay for procedures, but not for office visits, at higher levels than those paid by Medicare. Payment reform is essential to guarantee a healthy primary care base to the U.S. health care system."

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medicine journals primary care resource based relative value scale

Background and aims Physician reimbursement for services and thus income are largely determined by the Medicare Resource-Based Relative Value Scale. Patients' assessment of the value of physician services has never been considered in the calculation. This study sought to compare patients' valuation of health-care services to Medicare's relative value unit (RVU) assessments and to discover patients' perceptions about the relative differences in incomes across physician specialties.

Design Cross-sectional survey.

Participants and setting Individuals in select outpatient waiting areas at Johns Hopkins Bayview Medical Center.

Methods Data collection included the use of a visual analog 'value scale' wherein participants assigned value to 10 specific physician-dependent health-care services. Informants were also asked to estimate the annualized incomes of physicians in specialties related to the abovementioned services. Comparisons of (i) the 'patient valuation RVUs' with actual Medicare RVUs, and (ii) patients' estimations of physician income with actual income were explored using t-tests.

Outcomes Of the 206 eligible individuals, 186 (90%) agreed to participate. Participants assigned a significantly higher mean value to 7 of the 10 services compared with Medicare RVUs (P < 0.001) and the range in values assigned by participants was much smaller than Medicare's (a factor of 2 vs. 22). With the exception of primary care, respondents estimated that physicians earn significantly less than their actual income (all P < 0.001) and the differential across specialties was thought to be much smaller (estimate: $88 225, actual: $146 769).

Conclusion In this pilot study, patients' estimations of the value health-care services were markedly different from the Medicare RVU system. Mechanisms for incorporating patients' valuation of services rendered by physicians may be warranted.

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medicine journals primary care resource based relative value scale

Context Attention-deficit/hyperactivity disorder (ADHD)—characterized by symptoms of inattention and hyperactivity-impulsivity—is the most prevalent childhood psychiatric disorder that frequently persists into adulthood, and there is increasing evidence of reward-motivation deficits in this disorder.

Objective To evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of the brain dopamine reward pathway (mesoaccumbens).

Design, Setting, and Participants We used positron emission tomography to measure dopamine synaptic markers (transporters and D2/D3 receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls between 2001-2009 at Brookhaven National Laboratory.

Main Outcome Measures We measured specific binding of positron emission tomographic radioligands for dopamine transporters (DAT) using [11C]cocaine and for D2/D3 receptors using [11C]raclopride, quantified as binding potential (distribution volume ratio –1).

Results For both ligands, statistical parametric mapping showed that specific binding was lower in ADHD than in controls (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain. Region-of-interest analyses corroborated these findings. The mean (95% confidence interval [CI] of mean difference) for DAT in the nucleus accumbens for controls was 0.71 vs 0.63 for those with ADHD (95% CI, 0.03-0.13, P = .004) and in the midbrain for controls was 0.16 vs 0.09 for those with ADHD (95% CI, 0.03-0.12; P ≤ .001); for D2/D3 receptors, the mean accumbens for controls was 2.85 vs 2.68 for those with ADHD (95% CI, 0.06-0.30, P = .004); and in the midbrain, it was for controls 0.28 vs 0.18 for those with ADHD (95% CI, 0.02-0.17, P = .01). The analysis also corroborated differences in the left caudate: the mean DAT for controls was 0.66 vs 0.53 for those with ADHD (95% CI, 0.04-0.22; P = .003) and the mean D2/D3 for controls was 2.80 vs 2.47 for those with ADHD (95% CI, 0.10-0.56; P = .005) and d

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medicine journals psychiatry attention deficit disorder

Background Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes.

Methods In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction.

Results A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events.

Conclusions In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615 [controlled-trials.com] .)

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medicine journals cardiology pre-operative evaluation primary care

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Background

Depression is a major burden for the health-care system worldwide. Most care for depression is delivered by general practitioners (GPs). We assessed the rate of true positives and negatives, and false positives and negatives in primary care when GPs make routine diagnoses of depression.
Methods

We undertook a meta-analysis of 118 studies that assessed the accuracy of unassisted diagnoses of depression by GPs. 41 of these studies were included because they had a robust outcome standard of a structured or semi-structured interview.
Findings

50 371 patients were pooled across 41 studies and examined. GPs correctly identified depression in 47·3% (95% CI 41·7% to 53·0%) of cases and recorded depression in their notes in 33·6% (22·4% to 45·7%). 19 studies assessed both rule-in and rule-out accuracy; from these studies, the weighted sensitivity was 50·1% (41·3% to 59·0%) and specificity was 81·3% (74·5% to 87·3%). At a rate of 21·9%, the positive predictive value was 42·0% (39·6% to 44·3%) and the negative predictive value was 85·8% (84·8% to 86·7%). This finding suggests that for every 100 unselected cases seen in primary care, there are more false positives (n=15) than either missed (n=10) or identified cases (n=10). Accuracy was improved with prospective examination over an extended period (3–12 months) rather than relying on a one-off assessment or case-note records.
Interpretation

GPs can rule out depression in most people who are not depressed; however, the modest prevalence of depression in primary care means that misidentifications outnumber missed cases. Diagnosis could be improved by re-assessment of individuals who might have depression.

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medicine journals psychiatry depression primary care

In this issue of JAMA, Shuldiner and colleagues13 report the first careful genome-wide association study of clopidogrel response. The authors first studied a genetically homogenous population (the Old Order Amish), which minimizes the potential for confounding. They found that the loss-of-function cytochrome (CYP) P450 2C19*2 variant was associated with diminished effect of clopidogrel on inhibition of ADP-induced platelet aggregation. They then examined a separate population of patients undergoing PCI. Importantly, patients with this variant were twice as likely as those without the variant to sustain an ischemic event in the year following PCI. This elevated rate of ischemic events was largely confined to patients taking clopidogrel and who had the CYP2C19*2 polymorphism (vs those who did not have this polymorphism); the excess risk was not evident in patients not taking clopidogrel.

The authors demonstrated that the CYP2C19 polymorphisms were not associated with baseline platelet aggregation or response to aspirin but only affected aggregation in response to clopidogrel. Furthermore, there was a gene-dose effect, because persons heterozygous for the CYP2C19*2 allele had intermediate platelet inhibition after clopidogrel compared with CYP2C19*2 homozygous persons and noncarriers. These observations provide supportive evidence that the association between CYP2C19 and clopidogrel response may be real. Also, because the results of prior candidate gene studies and the current genome-wide association study approach are concordant, the likelihood of the association being true is high.13

Nevertheless, it remains possible that some proportion of the excess risk associated with this polymorphism is independent of clopidogrel and may have to do with another mechanism, such as impaired metabolism of other common cardiovascular drugs. More data from completed or future trials of clopidogrel in which genetic samples are obtained are needed to answer that question.14 Additionally, response to medication, much like cardiova

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medicine journals cardiology genetics

Context Clopidogrel therapy improves cardiovascular outcomes in patients with acute coronary syndromes and following percutaneous coronary intervention by inhibiting adenosine diphosphate (ADP)–dependent platelet activation. However, nonresponsiveness is widely recognized and is related to recurrent ischemic events.

Objective To identify gene variants that influence clopidogrel response.

Design, Setting, and Participants In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 healthy Amish persons and measured response by ex vivo platelet aggregometry. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention.

Main Outcome Measure ADP-stimulated platelet aggregation in response to clopidogrel treatment and cardiovascular events.

Results Platelet response to clopidogrel was highly heritable (h2 = 0.73; P < .001). Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18–CYP2C19–CYP2C9–CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance (P = 1.5 x 10–13 for rs12777823, additive model). The rs12777823 polymorphism was in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished clopidogrel response, accounting for 12% of the variation in platelet aggregation to ADP (P = 4.3 x 10–11). The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention (P = .02). Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death during 1 year of follow-up (hazard ratio, 2.42; 95% co

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medicine journals cardiology genetics

The discovery of the aquaporin-1 (AQP1) water channel by Agre and colleagues (1,2), which led to the Nobel Prize in 2003, has revolutionized the understanding of body fluid water regulation by the kidney. Moreover, the identification of other water channels in the kidney, namely AQP2, 3, and 4, along with urea and ion transporters, has allowed a much improved understanding of urinary dilution and concentration in health and disease at the cellular and molecular levels (3–8).

The AQP have provided a pathway for water movement across cellular membranes that could not be explained by simple diffusion through the lipid bilayers of cell membranes. AQP1 has been found to be expressed constitutively on both the apical and the basolateral membranes of the proximal tubule and descending limb of Henle’s loop. This water channel is not under control of vasopressin but is important in urinary concentration. Water efflux through these channels in the descending limb is an important factor in the countercurrent concentrating mechanism, and diminished maximal urinary osmolality has been shown in AQP1 knockout mice (9) and humans without the AQP1 gene (10).

AQP2, 3, and 4 are expressed in the cortical and medullary collecting duct (Figure 1) (11). AQP2 is found exclusively in the principal cells of the collecting tubule and collecting duct and is known to be regulated by arginine vasopressin (AVP). AQP3 and 4 are located on the basolateral membrane of the principal cells in the collecting duct. AQP3 knockout mice exhibit substantial polyuria secondary to vasopressin-resistant nephrogenic diabetes insipidus (NDI) (12). AQP3 is regulated by AVP. AQP4 predominates on the basolateral membrane of the inner medulla and is not regulated by AVP. AQP4 knockout mice also exhibit an NDI that is less severe than that observed in the AQP3 knockout mice (13). Whereas AQP3 and AQP4 constitute the exit channels for water movement across the basolateral membrane of the collecting duct, AQP2 is the water channel for water reabsorption across th

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medicine journals renal hyponatremia water homeostasis physiology

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In the current debate over health care reform, many observers are proposing new delivery structures to move U.S. health care away from fragmentation, poor performance, and dysfunction toward accountability for high-value care. Ideally, these new structures would promote clear accountability for both improving quality and controlling costs and would encourage health care professionals to organize themselves into teams working on behalf of patients. For such structures to be sustainable, however, the payment system must reward professionals for the quality and efficiency of services, rather than the quantity.

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medicine journals health reform

Background: Atrial fibrillation is the most common sustained arrhythmia. Medical treatment often fails to control symptoms.

Purpose: To compare the benefits and harms of radiofrequency catheter ablation and medical therapy in adults with atrial fibrillation.

Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials (2000 to December 2008) were searched for English-language reports of studies in adults.

Study Selection: 6 independent reviewers screened abstracts to identify longitudinal studies of adults with atrial fibrillation who underwent radiofrequency catheter ablation. Studies reported arrhythmia or other cardiovascular outcomes at least 6 months after ablation or any adverse events.

Data Extraction: Data were extracted by 1 of 4 reviewers and were verified by a cardiac electrophysiologist. Study quality and overall strength of evidence for each question were rated by 2 independent reviewers; disagreements were resolved by consensus.

Data Synthesis: 108 studies met eligibility criteria. Moderate strength of evidence (3 trials; n = 30 to 198) showed that radiofrequency ablation after a failed drug course was more likely than continuation of drug therapy alone to lead to maintained sinus rhythm. Low strength of evidence (4 trials [n = 30 to 137] and 1 retrospective study [n = 1171]) suggested that radiofrequency ablation improved quality of life, promoted avoidance of anticoagulation, and decreased readmission rates compared with medical treatment. Major adverse events occurred in fewer than 5% of patients in most of 84 studies.

Limitations: Study follow-up was generally 12 months or less. Large heterogeneity of applied techniques and reporting of outcomes precluded many definitive conclusions. Reporting of adverse events was poor. Publication and selective reporting biases could not be ruled out. Studies with small samples and studies reported in a language other than English were excluded.

Conclusion: Radiofrequency catheter ablation is effective for up to 12 months of rhythm contr

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medicine journals cardiology atrial fibrillation

Background: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.

Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.

Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.

Study Selection: Randomized, placebo-controlled, double-blinded human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.

Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies.

Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. NAI chemoprophylaxis decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.

Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.

Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis appears to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanes

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medicine journals infectious disease influenza

In the active-mirror group, seven of eight patients (88%) reported reduced pain (median change in visual-analogue score, –51 mm; range, –70 to –18). In the covered-mirror group, only one of eight patients (12%) reported reduced pain, two patients (25%) reported no change in the pain level, and five patients (62%) reported increased pain.

In the mental-imagery group, two of eight patients (25%) reported reduced pain and six patients (75%) reported increased pain. At 4 weeks, the scores for pain on the visual-analogue scale in the active-mirror group differed significantly from those in the covered-mirror group (P=0.002) and mental-imagery group (P<0.001 for both comparisons).

After the randomization period, 12 patients crossed over to active mirror therapy. After the crossover treatment period, 11 of the 12 patients (92%) who switched to active mirror therapy from either the covered-mirror group or the mental-imagery group had a significant reduction in pain (P=0.002 and P=0.004, respectively).

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medicine journals pain management physiatry alternative medicine

Background Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-{kappa}B ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis.

Methods We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than –2.5 but not less than –4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures.

Results As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001) — a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04) — a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) — a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab.

Conclusions Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791

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medicine journals endocrinology rheumatology osteoporosis

In the 1950s the payment divergence between generalists and specialists was institutionalized through the advent of the relative value scale. In 1952 the California Medical Association (CMA) became concerned that insurers would abandon the UCR system because of the wide variation in fees charged by different physicians. To avoid the UCR’s demise in favor of an insurer-determined fee schedule, the CMA created a Committee on Fees, which examined hundreds of services, assigned each a "service code," and defined for each service a relative value unit (RVU). For example, a brief follow-up office visit might have an RVU of 1, while a comprehensive hospital visit might have an RVU of 7. Payment would be based on the RVU multiplied by a "conversion factor," determined by each insurer, which turned a service with its associated RVUs into a fee for that service.

The RVUs set by the CMA committee reflected the fees for different services existing in the community in the early 1950s. Because patients tended to have insurance for procedural services provided by surgeons and imaging services performed by radiologists, fees for those specialists were already much higher per time spent than fees for PCP visits, which were rarely covered by insurance. In this way, a bias was embedded in the "relative value" of the RVU and exacerbated as new procedures (with higher RVUs) were added over time and as conversion factors increased. For example, if the conversion factor was 5 for a service in a Blue Shield plan, the follow-up office visit would be paid a fee of $5 (1 RVU x 5), while the comprehensive hospital visit would bring $35 (7 RVUs x 5), or a difference of $30. When the conversion factor increased to 10, the resultant fees would be $10 and $70, with a difference of $60. Thus, specialists gained both from a rise in the conversion factor and from the creation of new services with higher RVUs, which were rarely adjusted downward when physicians gained experience and procedures took less time.14

The CMA’s RVU system became the pre

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medicine journals primary care health reform resource based relative value scale

The ACCORD study, conducted at 77 sites in North America, incorporated three complementary strategies for intensive or standard control of blood sugar levels, blood pressure, or lipids in 10,251 adults. The blood pressure and lipid portions of the trial were scheduled to end on June 30, 2009. For diabetes treatment, physicians could choose from any of the approved drug classes.

The goal of the trial was for the intensive treatment group to reach a hemoglobin [A.sub.1c] level of less than 6% and for the standard treatment group to reach a level between 7.0% and 7.9%, but findings showed a 20% increased mortality risk in the intensive treatment group (N. Engl. J. Med. 2008;358: 2545-9). Analyses of the interim results could find no specific reason for the increased risk of death from intensive glycemic control.

According to data presented at the meeting, the excess mortality risk in the intensively treated patients occurred among those who failed to reach Hb[A.sub.1c] levels close to 6%, and under 7%. "This is a paradox, because the intensive treatment strategy was aimed at lowering Hb[A.sub.1c] yet increased the risk of death," Dr. Riddle said. "We don't know why this is, what it was about the participants themselves, or about the way they were treated. Other analyses are underway to try to identify this. But we think this has important clinical implications: that people who easily achieve Hb[A.sub.1c] values below 7% do not necessarily have an increase of cardiovascular risk by doing so. But the ones who struggle to improve their glucose control appear to be at risk. We need to learn more [about who these at-risk patients] are and what needs to be done differently for their treatment strategies."

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medicine journals endocrinology diabetes

Objectives. As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise-induced oxidative stress.

Design. This case–control study compared nine CFS patients to a gender-, age- and weight-matched control group of nine healthy sedentary subjects.

Interventions. All subjects performed an incremental cycling exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and evoked compound muscle potential (M-wave) recorded from vastus lateralis. Repetitive venous blood sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL-6 and TNF-α) and two Hsp (Hsp27 and Hsp70) at rest, during maximal exercise and the 60-min recovery period.

Results. Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their response to maximal exercise associated (i) M-wave alterations indicating reduced muscle membrane excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level, (iii) absence of significant increase in IL-6 and TNF-α, and (iv) delayed and marked reduction of Hsp27 and Hsp70 variations. The post-exercise increase in TBARS was accentuated in individuals having the lowest variations of Hsp27 and Hsp70.

Conclusions. The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.

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medicine journals chronic fatigue syndrome