Patients Of Long Duration Research Articles

Exploring Analysis Approaches for Using the Dopamine Transporter Striatal Binding Ratio in Early- to Mid-Stage Parkinson's Disease Modification Trials.

The dopamine transporter striatal binding ratio (DAT SBR) has been used as an outcome measure in Parkinson's disease (PD) trials of potential disease-modifying therapies; however, both patient characteristics and analysis approach potentially complicate its interpretation. The aim was to explore how well DAT SBR reflects PD motor severity across different striatal subregions and the relationship to disease duration, and side of onset. DAT SBR for the anterior and posterior putamen and caudate in both hemispheres was obtained using validated automated quantitative software on baseline scans of 132 patients recruited for the Exenatide PD2 and PD3 trials. Associations between mean and lateralized SBR subregions (posterior and anterior putamen and caudate) and summed and lateralized motor characteristics were explored using regression analysis. Analyses were repeated considering disease duration and limiting analysis to the less-affected hemisphere. Lateralized bradykinesia was most consistently associated with the loss of DAT uptake in the contralateral anterior putamen. There was much higher variance in the posterior putamen, and in all regions in those with longer duration disease, although bradykinesia remained robustly associated with anterior putaminal DAT uptake even in longer-duration patients. Restricting analyses to the less-affected side did not usefully reduce the variance compared to the overall cohort. These data suggest that DAT SBR could be a useful biomarker in disease-modifying trials, but a focus on anterior striatal subregions and incorporating disease duration into analyses may improve its utility.

Impact of preoperative symptom duration in patients undergoing lateral lumbar interbody fusion.

Few studies have examined the influence of preoperative symptom duration on clinical outcomes in patients undergoing lateral lumbar interbody fusion (LLIF) for degenerative conditions. Patients undergoing LLIF presenting with radiculopathy and/or neurogenic claudication were separated into two groups: preoperative symptom duration < 1-year (shorter duration) versus duration ≥ 1-year (longer duration). Patients undergoing surgery for trauma/malignancy/infection were excluded. Patient-reported outcome measures (PROMs) of Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), 12-Item Short Form Physical/Mental Component Score (SF-12 PCS/MCS), Patient Health Questionnaire-9 (PHQ-9), visual analog scale (VAS) back/leg, and Oswestry Disability Index (ODI) were collected at preoperative and postoperative time points. Eighty-two total patients, with 34 shorter-duration patients, were identified after propensity score matching for demographics. Longer-duration patients had higher estimated blood loss. All patients reported significant improvement in physical function, mental function, pain, and disability in at least one postoperative time point, except for SF-12 MCS in the shorter duration cohort. The longer duration cohort had higher MCID achievement in 12-week VAS back. Patients undergoing LLIF demonstrated significant postoperative improvement in physical function, mental function, pain, and disability outcomes independent of preoperative symptom duration. Both cohorts, when compared by preoperative symptom duration, demonstrated similar postoperative PROM scores. Patients with longer preoperative symptom duration had higher 12-week leg pain MCID achievement. These findings suggest that delayed time to surgery may not lead to inferior clinical outcomes in patients undergoing LLIF for degenerative conditions.

Persistent C-peptide levels and microvascular complications in childhood onset type 1 diabetes of long duration

AimsThe aim was to determine if persistent c-peptide in long duration childhood onset (<17 years) type 1 diabetes (T1D) related to microvascular complications. MethodsPittsburgh Epidemiology of Diabetes Complications (EDC) participants (n = 185) had serum c-peptide levels measured by Mercodia ultra-sensitive ELISA at the 25-year follow-up exam. Microvascular complications between those with and without detectable c-peptide were compared. ResultsEighteen (9.7%) participants had detectable median c-peptide levels of 3.8 (2.6, 12.2) pmol/L and did not differ from those without detectable levels. No differences in microalbuminuria, confirmed distal symmetric polyneuropathy, renal failure, or between those with one or more complications were found between the two groups. Proliferative retinopathy (PR) was marginally lower in those with detectable c-peptide (33.3% vs 55.1%, p = 0.08). However, those with c-peptide were somewhat less likely to have fasted for a full 8-h (66.7% vs. 84.9%, p = 0.09). Excluding those not fully fasted, PR no longer approached significance but macroalbuminuria became marginally lower in those with detectable levels (23.4% vs 0%, p = 0.07). ConclusionsLow levels of c-peptide in T1D patients of long duration were detected but were not strongly related to microvascular complications.

Patients with Risk Factors for Complications Do Not Require Longer Antimicrobial Therapy for Complicated Intra-Abdominal Infection

A prospective, multicenter, randomized controlled trial found that four days of antibiotics for source-controlled complicated intra-abdominal infection resulted in similar outcomes when compared with a longer duration. We hypothesized that patients with specific risk factors for complications also had similar outcomes. Short-course patients with obesity, diabetes, or Acute Physiology and Chronic Health Evaluation II ≥15 from the STOP-IT trial were compared with longer duration patients. Outcomes included incidence of and days to infectious complications, mortality, and length of stay. Obese and diabetic patients had similar incidences of and days to surgical site infection, recurrent intra-abdominal infection, extra-abdominal infection, and Clostridium difficile infection. Short- and long-course patients had similar incidences of complications among patients with Acute Physiology and Chronic Health Evaluation II ≥15. However, there were fewer days to the diagnosis of surgical site infection (9.5 ± 3.4 vs 21.6 ± 6.2, P = 0.010) and extra-abdominal infection (12.4 ± 6.9 vs 21.8 ± 6.1, P = 0.029) in the short-course group. Mortality and length of stay was similar for all groups. A short course of antibiotics in complicated intra-abdominal infection with source control seems to have similar outcomes to a longer course in patients with diabetes, obesity, or increased severity of illness.

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome

Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis. In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients. Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.

Impact of Atrial Fibrillation Duration on the Success of First-Time Concomitant Cox Maze Procedures

Atrial fibrillation (AF) duration is one of the most consistent predictors of Cox maze (CM) procedure failure. We examined the impact of AF duration on CM success in patients having first-time concomitant surgery. First-time concomitant CM was performed in 505 patients. Freedom from atrial arrhythmia (AA) and class I/III antiarrhythmic drug (AAD) data were collected prospectively. Patients with longer AF duration (≥ 5 years; n = 113) were compared with shorter duration (<5 years; n = 392) in primary analyses. The AF duration was examined as a continuous variable in regression analyses. Patients with longer AF duration were older (68.4 vs 65.1 years, p = 0.002) and in long-standing persistent AF (80% vs 36%, p < 0.001). Freedom from AA and AA off AAD was lower in longer duration patients at 1 year (80% vs 94%, p < 0.001; 74 vs 87%, p = 0.005) and 2 years (69 vs 90%, p < 0.001; 61 vs 81%, p = 0.001). Freedom from stroke or transient ischemic attack (TIA) was similar (96.1% vs 95.4%, p = 0.65). Adjusting for clinical and AF-associated factors, each 1-year increase in AF duration had 13% greater odds for failure at 1 year (odds ratio [OR], 1.13, p = 0.004) and 20% greater odds at 2 years (OR, 1.20, p < 0.001). Cryothermia as sole energy source attenuated the negative impact of AF duration on 1-year success. Longer AF duration significantly impacted CM success and may result from extensive tissue remodeling. Patients with longer AF duration can expect reasonable success rates, especially when on AAD, and low stroke rates during follow-up. Cryoablation may reduce AF duration impact on success compared with combined bipolar radiofrequency and cryothermia.

Low serum apolipoprotein A1/B ratio is associated with proliferative diabetic retinopathy in type 2 diabetes

The association between lipids and diabetic retinopathy (DR) remains unclear. Only a few studies have reported the association between proliferative diabetic retinopathy (PDR) and the serum concentrations of apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and apolipoprotein E (apoE). So we investigated the lipid profile in type 2 diabetic patients of long duration with very mild nonproliferative diabetic retinopathy (NPDR) or PDR. Serum samples were obtained from 25 type 2 diabetic patients with very mild NPDR and 25 type 2 diabetic patients with PDR, and the two groups were matched by diabetes duration and glycosylated hemoglobin (HbA(1c)) levels. The levels of total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apoA1, apoB, and apoE were measured by enzymatic colorimetric, surfactant, and immunotubidimetric method. Compared with PDR subjects, very mild NPDR subjects were characterized by increased HDL cholesterol (P = 0.0433) and apoA1 (P = 0.0290) levels, higher HDL cholesterol/LDL cholesterol (P = 0.0377) and apoA1/apoB (P = 0.0061) ratio in serum. There were significant associations between the decreased apoA1 and low apoA1/apoB ratio in serum and PDR. Even after adjustment for age, decreased apoA1 level (P = 0.0304) and low apoA1/apoB ratio (P = 0.0218) in serum were significantly associated with PDR in type 2 diabetic patients of over 15years' duration. Low apolipoprotein A1/apolipoprotein B ratio in serum was associated with PDR in type 2 diabetic patients of long duration.

Compliance with diet prescription can help management for Korean Type2 DM patients of long duration

Compliance with diet prescription can help management for Korean Type2 DM patients of long duration

Effects of an ankle-foot orthosis on balance performance in patients with hemiparesis of different durations

To examine the effects of an ankle-foot orthosis (AFO) on balance performance in patients with hemiparesis of short and long duration. Within-subject random order of intervention, cross-sectional study design. Medical centres and district hospitals. Forty-two subjects with hemiparesis of short duration (< six months) and 61 subjects of long duration ( > 12 months). The balance and gait ability of subjects were evaluated both with an AFO and without. The static and dynamic balance activities were evaluated by the Balance Master System, whereas the functional balance was assessed with the Berg Balance Scale. The speed and cadence were also measured during a 10-metre walk. Paired t-test was used to determine the effect of the AFO. In subjects with hemiparesis of short duration, we found that subjects wearing an AFO showed significant improvements in (1) weight-bearing distribution during quiet standing (p = 0.042, 95% confidence interval (CI) 0.521, 7.325), (2) body sway during standing on foam surface with eyes open (p = 0.020, 95% CI 0.020, 0.680) and eyes closed (p = 0.041, 95% CI 0.023, 0.921), (3) movement velocity during limit of stability test (LOS)--toward the affected side (p = 0.037, 95% CI - 0.978, - 0.042) and nonaffected side (p = 0.008, 95% CI -2.223, - 0.377), (4) maximal excursion toward the affected side (p= 0.042, 95% CI -19.546, -0.071), and (5) speed (p=0.028, 95% CI -0.204, -0.017) and cadence (p= 0.021, 95% CI - 22.983, - 1.864). Such effects were not observed in subjects with hemiparesis of long duration. For the subjects with hemiparesis of short duration, the AFO improves the symmetry in quiet and dynamic standing balances. It also increases speed and cadence. However, its effectiveness is minimal for patients of long duration.

Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus

This study evaluated the efficacy of rosiglitazone in non-obese and obese Korean type 2 diabetic patients of long duration. A total of 125 patients (M:F = 44:81, mean age: 58.4 ± 9.1 years, BMI: 24.2 ± 2.7 kg/m 2, duration of diabetes: 11.0 ± 6.4 years) were randomly allocated to 12 weeks of rosiglitazone treatment (4 mg per day) or a control group. Responders were defined as patients who experienced fasting plasma glucose (FPG) reduction of >20% or HbA 1c reduction of >1 (%). Rosiglitazone significantly improved glycemic control by reducing FPG and HbA 1c (−3.4 mmol/l and −1.1%, P < 0.001, respectively). It also significantly increased HOMA β-cell function (+9.7, P < 0.01) and QUICKI (+0.029, P < 0.001), and decreased HOMA IR (−1.73, P < 0.001). Females and those with higher waist–hip ratio made up a greater portion of rosiglitazone-responders. Responders (45 patients, 75%) also showed significantly higher FPG, HbA 1c, systolic blood pressures, fasting insulin levels and HOMA IR, and lower QUICKI than nonresponders. Among these parameters of responders, waist–hip ratio of non-obese subgroup, initial glycemic control of obese subgroup, and systolic blood pressure of both subgroups lost their significance after subdivision analysis. However, the baseline HOMA IR and QUICKI were significantly correlated with the response rate to rosiglitazone. Moreover, in multiple logistic regression analysis, HOMA IR and QUICKI retained their significance as the independent predictors. Even in Korean type 2 diabetic patients of long duration but with relatively preserved β-cell function, rosiglitazone improved glycemic control, insulin sensitivity, and β-cell function. In this ethnic group, female gender, central obesity, and especially severe insulin resistance were identified as predictive clinical parameters of rosiglitazone-responders.

A meta-analysis of structural and functional brain imaging in dementia of the Alzheimer's type: a neuroimaging profile.

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimer's disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimer's dementia and should aid in the positive identification of AD.

ENOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy.

Genetic factors may be involved in the development, and particularly in the severity, of diabetic retinopathy (DR), in addition to chronic hyperglycaemia. Increased nitric oxide generation has been suggested to play a significant role in the pathogenesis of DR. To examine whether the eNOS4 is involved in the risk of severe DR, 200 unrelated Caucasian Type 1 diabetic patients of long duration were randomly selected (M/F 103/97, age 44.4 +/- 12.4 years, diabetes duration 27.7 +/- 10.0 years, body mass index 24.3 +/- 3.4 kg/m2, HbA1c 8.6 +/- 1.3%). The eNOS4 polymorphism was analysed by polymerase chain reaction, and DR by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (proliferative or pre-proliferative) DR. The genotype distribution of eNOS4b/b (wild-type), eNOS4b/a (heterozygous) and eNOS4a/a (homozygous) was 72%, 24.5% and 3.5%, respectively. Frequency of eNOS4a/a was significantly lower in patients with severe DR (n = 0) when compared with controls (n = 7, odds ratio (OR) = 0 (95% confidence interval (CI) = 0.5-0.74), P = 0.02). eNOS4b/b was more frequent in patients with severe DR (n = 80) when compared with controls (n = 64, OR = 2.1 (95% CI = 1.1-4.12), P = 0.032). Frequency of eNOS4b/a was not different between the study (n = 21) and control groups (n = 28, ns). The allelic frequencies between the study and control groups were different (4b: n = 181 vs. n = 156, respectively, OR = 2.3 (95% CI = 1.27-4.25), P = 0.005; 4a: n = 21 vs. n = 42, respectively, OR = 0.4 (95% CI = 0.24-0.79), P = 0.005). We demonstrate in Caucasians with Type 1 diabetes that (i) eNOS4a/a is associated with absent or non-severe DR, and (ii) eNOS4b/b is associated with severe DR.

The relationship between peripheral T cell reactivity to insulin, clinical remissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus.

Antigenic proliferative responses of peripheral blood mononuclear cells (PBMC) to insulin were studied in 44 type 1 new-onset diabetic subjects. Of them, 14 (32%) had a stimulation index (> or =3) above the mean + 3 SD of 39 healthy controls and of 7 of 15 (47%) diabetic patients of long duration (P = 0.001). Responses to insulin were not dictated by specific major histocompatibility complex class II association and were not observed in normal subjects with diabetes-associated human leukocyte antigen-DR/DQ alleles. Whereas no relation of PBMC reactivity with insulin autoantibodies was found, there was a positive correlation with the presence of at least one of the four autoantibodies tested and with IA-2 antibody. An interesting finding was that the proportion of patients with subsequent low insulin requirement, up to 24 months, was significantly higher in patients who showed PBMC reactivity to insulin (8 of 8) than in those who did not (10 of 24, 42%; P = 0.004). The former had a higher mean stimulation index than the latter (3.3+/-2.6 vs. 1.5+/-0.6; P = 0.006). Furthermore, interleukin-4 (IL-4) production was lower in type 1 diabetic patients who proliferated to insulin than in those who did not (23+/-15 vs. 64+/-47 pg/mL; P = 0.04), but interferon-gamma, IL-2, and IL-10 productions were similar. In conclusion, these results suggest that proliferation to insulin may reflect the presence of an higher residual beta-cell mass.

Alterations in T-lymphocyte subpopulations in type I diabetes. Exploration of genetic influence in identical twins.

To evaluate factors influencing the alteration in subsets of T-lymphocytes, we studied 24 pairs of identical twins discordant for insulin-dependent (type I) diabetes mellitus. Subsets were assessed by monoclonal antibodies and a pure preparation of peripheral blood mononuclear cells obtained by centrifugation of heparinized whole blood with a Ficoll/Triosil gradient. In 12 pairs studied within 5 yr of diagnosis, we observed a reduction in the percentage of cells reacting with OKT8 (recognizing the CD8 antigen present on the suppressor/cytotoxic subset) (P less than .05), but a similar level was detected in their nondiabetic cotwins. In 12 pairs studied greater than 5 yr after the diagnosis and in whom the nondiabetic twin is less likely to develop diabetes, the percentage of cells reacting with OKT8 was reduced in both the diabetic (P less than .05) and the nondiabetic (P less than .01) twins. Reductions were also seen with OKT3 (recognizing the CD3 antigen present on the total T-lymphocyte population) and OKT4 (recognizing the CD4 antigen present on the helper/inducer subset), but only in the diabetic twins from the group with longer discordance. We conclude that a reduced percentage of suppressor/cytotoxic cells is associated with type I diabetes, but the reduction appears to be genetically determined. Total T-lymphocytes are also reduced but mainly in the helper/inducer subset and only in diabetic patients of long duration. Such a reduction cannot therefore be primarily genetically determined.

Duration of hospitalization and changes in responses to favorable and unfavorable scales with typical- and best-period instructions.

This study investigated changes in responses of hospitalized Ss when both desirable and undesirable scales were given twice with instructions for Ss to first report how they felt recently and secondly how they felt during a best period. When relationships between changes in scores and duration of hospitalization were determined, a conjoint increase in desirable and a decrease in undesirable scores was predictive of short hospitalization. Changes in desirable scores only were not significantly correlated with outcome but improved scores with best-period instructions were more frequent with short than longer-duration patients. Changes in two undesirable scores were signficantly correlated with outcome. Findings suggest that patients who frankly reveal shortcomings and distresses for a recent period but who obtain desirable and undesirable scores within “normal” limits for a best period are likely to have favorable prognosis.

Vascular disease in juvenile diabetic patients of long duration: a preliminary report.

Vascular disease in juvenile diabetic patients of long duration: a preliminary report.