Citations

The first 325 Exeter Universal stems (309 patients) implanted at the originating centre were inserted between March 1988 and February 1990 by a group of surgeons with differing experience. In this report we describe the clinical and radiological results at a mean of 15.7 years (14.7 to 17.3) after operation with no loss to follow-up. There were 97 patients (108 hips) with replacements still in situ and 31 (31 hips) who had undergone a further procedure. With an endpoint of revision for aseptic loosening, the survivorship at 17 years was 100% and 90.4% for the femoral and acetabular component, respectively. The mean Merle D’Aubigné and Postel scores at review were 5.4 (sd 0.97) for pain and 4.5 (sd 1.72) for function. The mean Oxford score was 38.4 (sd 9.8) (0 to 48 worst-to-best scale) and the mean combined Harris pain and function score was 73.2 (sd 16.9). Radiological review showed excellent preservation of bone stock in the proximal femur and no failures of the femoral component.

Abstract Rationale In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem. Objectives To determine the effect of lung volume reduction surgery (LVRS) on a composite endpoint consisting of the occurrence of death or a clinically meaningful decline in QoL defined as an increase of at least eight points in the St. George's Respiratory Questionnaire total score from the National Emphysema Treatment Trial. Methods In patients with chronic obstructive pulmonary disease and emphysema randomized to receive medical treatment (n = 610) or LVRS (n = 608), we analyzed the survival to the composite endpoint, the hazard functions and constructed prediction models of the slope of QoL decline. Measurements and Main Results The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P < 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS. Conclusions LVRS has a significant effect on the composite QoL-survival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe–predominant emphysema.

AbstractPatient activity level may be an important prognostic variable relating to outcome in patients with shoulder disorders. The purpose of this cross‐sectional study was to test the hypothesis that a shoulder activity scale will detect differences in shoulder activity based on the patient diagnosis and age. A total of 157 patients of four academic orthopedic surgeons with a diagnosis of rotator cuff disease (86), glenohumeral instability (31) or osteoarthritis (40) were asked to fill out a previously validated shoulder activity scale and the ASES shoulder questionnaire. The patient's diagnosis, gender and age were recorded. The activity level was significantly higher in patients with instability than in patients with rotator cuff disease or osteoarthritis. Patients with rotator cuff disease were significantly more active than patients with osteoarthritis. Linear regression of activity level on patient age and diagnosis demonstrated a statistically significant relationship between activity level and both independent variables. Diagnosis influenced activity level independent of age. This is the first study to document diagnosis‐based differences in the shoulder activity level of patients with different shoulder disorders. Shoulder activity level should be evaluated as a prognostic variable in studies of patients with shoulder disorders that may predict outcome and guide treatment in these patients.

Background— The Epidemiology of Diabetes Interventions and Complications (EDIC) study, a prospective observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort, reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes mellitus. We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy (CAN) in former DCCT intensive and conventional therapy subjects 13 to 14 years after DCCT closeout. Methods and Results— DCCT autonomic measures (R-R variation with paced breathing, Valsalva ratio, postural blood pressure changes, and autonomic symptoms) were repeated in 1226 EDIC subjects in EDIC year 13/14. Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjustment for DCCT baseline covariates, duration in the DCCT, and quantitative autonomic measures at DCCT closeout. In EDIC year 13/14, the prevalence of CAN using the DCCT composite definition was significantly lower in the former intensive group versus the former conventional group (28.9% versus 35.2%; P =0.018). Adjusted R-R variation was significantly greater in the former DCCT intensive versus the former conventional group (29.9 versus 25.9; P <0.001). Prior DCCT intensive therapy reduced the risks of incident CAN by 31% (odds ratio, 0.69; 95% confidence interval, 0.51 to 0.93) and of incident abnormal R-R variation by 30% (odds ratio, 0.70; 95% confidence interval, 0.51 to 0.96) in EDIC year 13/14. Conclusions— Although CAN prevalence increased in both groups, the incidence was significantly lower in the former intensive group compared with the former conventional group. The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout.

As humans age, the tonic level of activity in sympathetic vasoconstrictor nerves increases and may contribute to age-related increases in blood pressure. In previous studies in normotensive young men with varying levels of resting sympathetic nerve activity, we observed a balance among factors contributing to blood pressure regulation, such that higher sympathetic activity was associated with lower cardiac output and lesser vascular responsiveness to α-adrenergic agonists, which limited the impact of high sympathetic activity on blood pressure. In the present study, we tested the hypothesis that older normotensive men would exhibit a similar balance among these variables (sympathetic nerve activity, cardiac output, and α-adrenergic responsiveness) but that this balance would be shifted toward higher sympathetic nerve activity values. We measured muscle sympathetic nerve activity, cardiac output, arterial pressure, and forearm vasoconstrictor responses in 17 older men and compared these with previous data collected in 14 younger men. Muscle sympathetic activity (burst incidence) was positively related to diastolic blood pressure in the older men ( r =0.49; P =0.05); this relationship was not observed in young men. In addition, there was no relationship between cardiac output and muscle sympathetic activity ( r =0.29; P >0.05) or between muscle sympathetic activity and vasoconstrictor responses in the older men (eg, norepinephrine: r =−0.21; P >0.05). Although our older subjects were normotensive, the relationship between muscle sympathetic nerve activity and diastolic blood pressure and the lack of “balance” among the other variables suggest that these changes with aging may contribute to the risk of sympathetically mediated hypertension in older humans.

Lenalidomide is the first karyotype-selective therapeutic approved for the treatment of myelodysplastic syndromes (MDS) owing to high rates of erythroid and cytogenetic response in patients with chromosome 5q deletion [del(5q)]. Although haploinsufficiency for the RPS14 gene and others encoded within the common deleted region (CDR) have been implicated in the pathogenesis of the del(5q) phenotype, the molecular basis of the karyotype specificity of lenalidomide remains unexplained. We focused our analysis on possible haplodeficient enzymatic targets encoded within the CDR that play key roles in cell-cycle regulation. We show that the dual specificity phosphatases, Cdc25C and PP2Acα, which are coregulators of the G 2 -M checkpoint, are inhibited by lenalidomide. Gene expression was lower in MDS and acute myeloid leukemia (AML) specimens with del(5q) compared with those with alternate karyotypes. Lenalidomide inhibited phosphatase activity either directly (Cdc25C) or indirectly (PP2A) with corresponding retention of inhibitory phospho-tyrosine residues. Treatment of del(5q) AML cells with lenalidomide induced G 2 arrest and apoptosis, whereas there was no effect in nondel(5q) AML cells. Small interfering RNA (shRNA) suppression of Cdc25C and PP2Ac α gene expression recapitulated del(5q) susceptibility to lenalidomide with induction of G 2 arrest and apoptosis in both U937 and primary nondel(5q) MDS cells. These data establish a role for allelic haplodeficiency of the lenalidomide inhibitable Cdc25C and PP2Acα phosphatases in the selective drug sensitivity of del(5q) MDS.

In this study, 65% (132/195) of level B/C obstetric recommendations are amenable to randomized clinical trials (RCTs) and seven were identified as most needed. The purpose of the survey was to evaluate levels B and C recommendations in obstetric practice bulletins (PBs) regarding the feasibility of performing RCT to elevate each subject to level A evidence. Eleven geographically dispersed physicians with experience in research reviewed levels B and C recommendations for the ethical and logistical feasibility of performing an RCT. In the 35 obstetric PBs, 195 level B/C recommendations were reviewed. The majority considered 47 (24%) topics unethical for an RCT and thought 16 (11%) did not need an RCT, thus leaving 132 (67%) levels B and C recommendations available for an RCT. Two-thirds of levels B and C recommendations in obstetric PB are amenable to RCTs and potentially becoming level A evidence.