When data restricted to patients receiving transfusions are analyzed, and no data absent from the actual investigations are introduced, leukoreduced transfusions substantially and significantly reduce the odds of postoperative infection by approximately 50 percent. These results demonstrate the importance of including only scientifically valid data in clinical trials and meta-analyses. The intention-to-treat principle should never lead to inclusion of data not actually derived from experimental results.

Background: Motor fluctuations and dyskinesias can cause disability and reduce quality of life for patients with Parkinson disease (PD).Objectives: To evaluate factors associated with the development of motor fluctuations and dyskinesias and to assess the sequence in which they occur in individual patients.Design: We performed a retrospective analysis of data from a randomized clinical trial comparing pramipexole dihydrochloride and levodopa as initial treatment for PD. Subjects were followed up for 48 to 58 months and evaluated at 3-month intervals for the presence of motor fluctuations and dyskinesias.Setting: Academic and private practices.Patients: Three hundred one patients with early Parkinson disease were enrolled in this study between October 2, 1996, and August 21, 1997, and were observed through August 24, 2001, when the last patient enrolled completed 4 years of follow-up.Main Outcome Measures: Order of appearance of motor fluctuations and dyskinesias, time to the first occurrence of motor fluctuations, and time to the first occurrence of dyskinesias.Results: One hundred eighty-nine subjects (62.8%) developed motor complications. Of these, 71 (37.6%) developed fluctuations but not dyskinesias, 23 (12.2%) developed dyskinesias but not fluctuations, 48 (25.4%) developed fluctuations before dyskinesias, 33 (17.5%) developed dyskinesias before fluctuations, and 14 (7.4%) developed both at the same time. Factors significantly associated with earlier occurrence of dyskinesia were Hoehn and Yahr stage of 2 or higher, cumulative levodopa dose, cumulative levodopa equivalent dose (levodopa plus pramipexole), and occurrence of motor fluctuations. Pramipexole treatment was associated with later occurrence of dyskinesias. Factors associated with earlier occurrence of motor fluctuations were cumulative levodopa dose, cumulative levodopa equivalent dose, and occurrence of dyskinesias. Factors associated with later occurrence of motor fluctuations were age at onset of 65 years or older and pramipexole treatment.Conclusions: Higher cumulative levodopa doses and higher cumulative levodopa equivalent doses (levodopa plus pramipexole) were associated with the earlier occurrence of motor complications. Motor fluctuations and dyskinesias appear to be interrelated because the presence of one is associated with the earlier development of the other.

The Unified Batten Disease Rating Scale (UBDRS) is a reliable instrument that effectively tests for neurologic function in blind and demented patients. In its current form, the UBDRS is useful for monitoring the diverse clinical findings seen in Batten disease.

OBJECTIVE -To examine the effect of aging on insulin secretion (first-and second-phase insulin release) and insulin sensitivity in people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT).RESEARCH DESIGN AND METHODS -First-and second-phase insulin secretion and insulin sensitivity were assessed in hyperglycemic clamp experiments in 266 individuals with NGT and 130 individuals with IGT, ranging in age from ϳ20 to ϳ70 years. Changes in ␤-cell function were compared using the disposition index to adjust for differences in insulin sensitivity.RESULTS -As expected, both phases of insulin release and insulin sensitivity were reduced in individuals with IGT (all P Ͻ 0.01). Insulin sensitivity was not independently correlated with age in either group. In people with NGT, the disposition index for first-and second-phase insulin release decreased similarly at a rate of ϳ0.7% per year. In people with IGT, the disposition indexes for first-and second-phase insulin release decreased at greater rates (ϳ2.2 and 1.4% per year, P ϭ 0.002 and 0.009, respectively, vs. NGT), with the decrease in first phase being greater than that of second phase (P ϭ 0.025).CONCLUSIONS -Insulin secretion (both first and second phase) normally decreases at a rate of ϳ0.7% per year with aging; this decrease in ␤-cell function is accelerated about two-fold in people with impaired glucose tolerance-first phase to a greater extent than second phase. Finally, aging per se has no effect on insulin sensitivity independent of changes in body composition. Diabetes Care 31:539-543, 2008

Fibroblast strains were derived from two regions of the lower genital tract of localized provoked vulvodynia (LPV) cases and pain-free controls. Sixteen strains were derived from four cases and four controls, age and race matched, following pre-sampling mechanical pain threshold assessments. Strains were challenged with six separate stimuli: live yeast species (C. albicans, C. glabrata, C. tropicalis, and S. cerevisiae), yeast extract (zymosan), or inactive vehicle. Production of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) were pro-inflammatory response measures. Highest IL-6 and PGE2 occurred with vestibular strains following C. albicans, C. glabrata, and zymosan challenges, resulting in the ability to significantly predict IL-6 and PGE2 production by genital tract location. Following C. albicans and C. glabrata challenge of all sixteen fibroblast strains, adjusting for dual sampling of subjects, PGE2 and IL-6 production significantly predicted the pre-sampling pain threshold from the genital tract site of sampling. At the same location of pain assessment and fibroblast sampling, in situ immunohistochemical (IHC)(+) fibroblasts for IL-6 and Cox-2 were quantified microscopically. The correlation between IL-6 production and IL-6 IHC(+) was statistically significant yet biological significance is unknown because of the small number of IHC(+) IL-6 fibroblasts identified. A low fibroblast IL-6 IHC(+) count may result from most IL-6 produced by fibroblasts existing in a secreted, extracellular state. Enhanced, site-specific, innate immune responsiveness to yeast pathogens by fibroblasts may be an early step in LPV pathogenesis. Fibroblast strain testing may offer an attractive/objective marker of LPV pathology in women with vulvodynia of inflammatory origin.

I.

IntroductionClinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels.MethodsThis was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was >2.8 (not in remission).ResultsOf 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline.ConclusionsIn a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial visit. Requiring an elevation in APR levels as a criterion for inclusion of RA patients in studies of experimental agents may exclude some patients with active disease.

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