Gender-matched US Research Articles

Survival Benefit of Adjuvant Radiotherapy in Elderly Patients with WHO Grade III Meningioma

The benefit of adjuvant radiotherapy (RT) is uncertain in elderly patients diagnosed with World Health Organization (WHO) grade III meningiomas. The US National Cancer Database was used to identify elderly patients (aged over 60) with histologically confirmed WHO grade III meningiomas who underwent surgery with or without adjuvant external beam RT. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard models, and propensity score-matched analysis. Among the 254 patients who met inclusion criteria, 151 (58.4%) underwent surgery followed by RT and103 (41.6%) surgery without RT. The 5-year relative survival rate was 57.8% (95% confidence interval [CI], 38.7%-85.4%) in the adjuvant RT group and 38.1% (95% CI, 21.9%-55.9%) in the group without RT when compared with age- and gender-matched US population. Adjuvant RT was associated with longer OS on both univariate (P= 0.011) and multivariable analyses (adjusted hazard ratio [AHR],0.663; 95% CI, 0.449-0.978; P= 0.038). However, adjuvant RT did not significantly improve OS in a propensity score-matched analysis (P= 0.271) after matching the 2 cohorts on age, race, comorbidity, extent of resection, and tumor size. In patients who underwent subtotal resection or biopsy (n= 106), adjuvant RT significantly benefited OS on univariate analysis (P=0.023), but did not show statistically significant benefit on multivariate analysis (AHR, 0.594; 95% CI, 0.337-1.046; P= 0.071). Adjuvant RT was not associated with improved OS in the elderly patients who underwent gross total resection (AHR, 0.764; 95% CI, 0.434-1.344; P=0.350). Adjuvant external beam RT may not provide any survival benefit for elderly patients with WHO grade III meningioma after gross total resection.

Survival after Aortic Valve Replacement for Aortic Regurgitation: Prediction from Preoperative Contractility Measurement

Background: Noninvasive measurement of myocardial contractility (end-systolic wall stress-adjusted change in left ventricular ejection fraction from rest to exercise [ΔLVEF – ΔESS]) predicts heart failure, subnormal LVEF_rest, and sudden death in asymptomatic patients with chronic severe aortic regurgitation (AR). Here we assess the relation of preoperative ΔLVEF – ΔESS to survival after aortic valve replacement (AVR). Methods: Patients who underwent AVR for chronic, isolated, pure severe AR (n = 66) were followed for 13.0 ± 6.4 event-free years. Preoperative ΔLVEF – ΔESS (from combined echocardiographic and radionuclide cineangiographic data) enabled cohort stratification into 3 terciles (–1 to –11% [normal or mild] contractility deficit, –12 to –16% [moderate], and ≤–17% [severe], identical with segregation in our earlier study) to relate preoperative contractility to postoperative survival and to age- and gender-matched US census data. Results: Since AVR, 22 patients died (average annual risk [AAR] for all-cause mortality for the entire co hort = 3.15%). Preoperative ΔLVEF – ΔESS predicted postoperative survival (p = 0.009, log rank test). By contractility terciles, all-cause AARs were 1.44, 2.58, and 6.40%. Survival was lower than among US census comparators (p < 0.02), but the “mild” tercile was indistinguishable from census data (p = ns). By multivariable Cox regression, survival prediction by pre-AVR ΔLVEF – ΔESS was independent of, and superior to, prediction by age at surgery, gender, preoperative functional class, LVEF_rest, LVEF_exercise, change in LVEF_{rest to exercise}, and LV diastolic or systolic dimensions (p ≤ 0.01, pre-AVR ΔLVEF – ΔESS vs. other covariates). Conclusion: In severe AR, preoperative contractility predicts post-AVR survival and may be prognostically superior to clinical, geometric and performance descriptors, potentially impacting on patient selection for surgery.

Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured?

The concept of applying all active therapeutic agents in Total Therapy (TT) clinical trials for newly diagnosed multiple myeloma was pursued with the intent of developing curative treatment. The results of TT1 (n=231), TT2 (n=668) without or with thalidomide and TT3 with added bortezomib (n=303) have been reported. An update with median follow-up times of 17.1, 8.7 and 5.5 years, respectively, is provided. Conditional overall survival (OS) analysis from a 4-year landmark was applied to account for earlier protocol failure owing to disease aggressiveness and toxicities. Cumulative relative survival was computed in the context of age- and gender-matched US population, and interval-specific relative survival ratios were estimated to determine times to normal survival expectation. Based on Cox model-adjusted statistics, OS, progression-free survival and complete-response duration all improved with the transitions from TT1 to TT2 to TT3; improvement was also evident from time-to-progression estimates, 4-year conditional survival data and cumulative relative survival. Interval-specific relative survival normalized progressively sooner, reaching near-normal levels with TT3 in patients who attained complete response. Thus, a strategy using all myeloma-effective agents up-front seems effective at preventing, in progressively larger patient cohorts over time, the outgrowth of resistant tumor cells that account for ongoing relapses.

Prognosis of a Normal Positron Emission Tomography 82Rb Myocardial Perfusion Imaging Study in Women with No History of Coronary Disease

Objectives: Myocardial perfusion imaging (MPI) with positron emission tomography (PET) has advantages over single-photon emission computerized tomography, particularly for women. This investigation was undertaken to define the prognosis of a normal stress PET MPI study in women. Methods:The cohort comprised 457 women evaluated for suspected coronary artery disease (CAD) who had normal pharmacologic stress ⁸²Rb PET MPI. No patient had clinically evident CAD. Kaplan-Meier estimates were used to determine death and initial nonfatal cardiac event rates over 7 years. Log rank tests were used to assess the relationship between baseline cardiac risk and events during follow-up, and to contrast survival in the cohort with age- and gender-matched US census comparators. Results: During follow-up, there were 11 deaths (all nonischemic), 3 nonfatal myocardial infarctions, 3 percutaneous coronary interventions and 1 coronary artery bypass operation. Average risks of death and initial nonfatal cardiac events were 0.72 and 0.47% per year, respectively. Cardiac events were associated with a history of diabetes (p < 0.0003) and a family history of CAD (p < 0.05). Conclusion: A normal cardiac PET study is associated with a very low rate of future cardiac events. Women with diabetes and a strong family history of CAD are more likely to sustain events and require close surveillance for the development of coronary disease.

Quality of Life and Chronic Gvhd Severity According to the NIH Criteria: Results From the Chronic Gvhd Consortium

AbstractAbstract 393Chronic graft-versus-host disease (cGVHD) can negatively impact quality of life (QOL) following allogeneic hematopoietic cell transplantation (HCT). Whether the new NIH cGVHD global severity grading correlates with patient reported QOL is not known. In a prospectively assembled multi-center observational cohort study of adult HCT recipients with cGVHD, we examined the relationship between cGVHD severity according to NIH criteria and patient-reported QOL. Major objectives of this analysis were: (1) Describe the relationship between cGVHD severity and patient reported QOL; (2) compare QOL in HCT recipients with cGVHD to US population normative data; (3) compare QOL in HCT recipients with cGVHD to patients with other chronic health conditions; and (4) investigate the ability of SF-36 and FACT-BMT QOL instruments to discriminate cGVHD severity. This analysis included 298 patients with cGVHD who were enrolled at a median of 12.3 months from HCT. Overall, 54% patients were diagnosed < 3 months before enrollment. 56% had classic and 44% had overlap cGVHD. Organs most commonly involved included skin (63%), mouth (61%), eye (50%), and liver (50%). 31 (10%) had mild, 175 (59%) had moderate and 92 (31%) had severe cGVHD. Univariable modeling confirmed the relationship between cGVHD severity and QOL outcomes (SF-36 and FACT-BMT composite scores and subscales). Among other considered disease-, transplantation-, and socio-demographic variables, only age was significantly correlated with QOL (physical functioning and the physical component score (PCS) of the SF-36 instrument). Multivariable linear regression analysis adjusting for age at enrollment showed QOL measures, especially involving physical functioning, to differ according to cGVHD severity. For example, controlling for age, the average physical component score (PCS) of the SF-36 was 5.6 points higher for mild cGVHD compared to severe cGVHD (p < 0.01) and 3.2 points higher for moderate cGVHD compared to severe cGVHD (p = 0.02). In comparison to age- and gender-matched US population normative data for SF-36, mean scores for cGVHD cohort members were significantly lower for physical functioning, role-physical, bodily pain, general health, vitality, social functioning, and PCS. There were no significant differences observed in the domains of role-emotional, mental health, or MCS. We also compared the mean SF-36 scores (PCS and MCS) of cGVHD patients with those reported for other chronic health conditions: Patients with moderate and severe cGVHD had PCS scores comparable to scores reported for systemic sclerosis, systemic lupus erythematosis, and multiple sclerosis, and greater impairment compared to common conditions such as diabetes, hypertension, and chronic lung disease (see figure). MCS scores of those with severe cGVHD rivaled MCS scores reported with clinical depression, while mild and moderate cGVHD MCS scores were comparable to that of the general population. Discriminative accuracy of the QOL instruments (SF-36 and FACT-BMT) was assessed utilizing an extension of the concordance index to an ordinal gold standard (cGVHD severity). The concordance index was modest (∼0.60) for all QOL scales examined, with no significant differences between the QOL instruments' discriminative ability. We conclude that, while physical components of self-reported quality of life are lower on average for patients with more severe cGVHD, the extent of impairment and symptom burden represented by cGVHD severity are not solely captured by differences in quality of life. Future analyses will evaluate sensitivity to change and may help identify the better instrument to use in this population. In summary, NIH consensus criteria global cGVHD severity is independently associated with patient reported QOL, with worsening QOL for increasing severity of cGVHD. Patients with moderate to severe cGVHD have poor QOL, comparable to patients with other with immune mediated disorders, and much worse than general population norms. We hypothesize that better prevention and control of cGVHD has the potential to not only decrease morbidity and mortality but also to significantly improve QOL. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Minimally invasive aortic valve replacement in octogenarian, high-risk, transcatheter aortic valve implantation candidates

Risk-stratifying algorithms are currently used to determine which patients may be at prohibitive risk for surgical aortic valve replacement, and thus candidates for transcatheter aortic valve implantation. Minimally invasive surgical approaches have been successful in reducing morbidity and improving survival after aortic valve replacement, especially in octogenarians. We documented outcomes after minimally invasive aortic valve replacement in high-risk octogenarians who may be considered candidates for percutaneous/transapical aortic valve replacement. From 1996 to 2009, minimally invasive aortic valve replacement was performed in 249 consecutive octogenarians. We used the modified European System for Cardiac Operative Risk Evaluation and Society of Thoracic Surgeons score to risk-stratify patients and characterize all early and late results. The mean age at operation was 84±3 (range 80-95) years, and 111 patients (45%) were male. Twenty-one percent (n=52) had previous cardiac surgery. Operative mortality was 3% (n=8/249). The median modified European System for Cardiac Operative Risk Evaluation (11%; interquartile range, 6-14) and Society of Thoracic Surgeons score (10.5%; interquartile range, 7-17) were not predictive of 30-day mortality in this cohort of patients (European System for Cardiac Operative Risk Evaluation c-index=0.527, P=.74, Society of Thoracic Surgeons score c-index=0.67, P=.18). Despite their poor predictive power, the Society of Thoracic Surgeons score and European System for Cardiac Operative Risk Evaluation were correlated with each other (r=0.40, P<.0001). Postoperative complications included stroke in 10 patients (4%), pneumonia in 3 patients (1%), renal failure requiring dialysis in 2 patients (1%), cardiac arrest in 2 patients (1%), pulmonary embolism in 1 patient (1%), and sepsis in 1 patient (1%). Follow-up was available for 238 patients (96%) and extended up to 12 years. Overall, long-term survival after minimally invasive aortic valve replacement at 1, 5, and 10 years was 93%, 77%, and 56%, respectively. There was no significant difference in long-term survival compared with that of a US age- and gender-matched population (standardized mortality ratio, 1.01; 95% confidence interval, 0.76-1.37; P=.88). A multivariate Cox-proportional hazards model indicated that increasing age (hazard ratio, 1.10; P=.008) and severe chronic obstructive pulmonary disease (hazard ratio, 2.52; P<.007) were significant predictors of survival. By using these factors, a clinical prediction model (P=.02) was developed and demonstrated that low-risk patients (first quartile prediction score) had 1-, 5-, and 8-year survival of 94%, 84%, and 67%, whereas high-risk patients (third quartile prediction score) had 1-, 5-, and 8-year survival of 89%, 74%, and 49%, respectively. Patients thought to be high-risk candidates for surgical aortic valve replacement have excellent outcomes after minimally invasive surgery with long-term survival that is no different than that of an age- and gender-matched US population. These data provide a benchmark against which outcomes of transcatheter aortic valve implantation could be compared.

Evidence of persistent neurologic injury following thrombotic thrombocytopenic purpura

Despite improvements in our understanding of the pathophysiology of thrombotic thrombocytopenic purpura (TTP), little data exist regarding the long-term sequelae following a diagnosis of TTP. We present the results of a comprehensive evaluation of neurologic injury that included a magnetic resonance imaging (MRI), a neurocognitive testing, and an evaluation of health-related quality of life. Twenty-seven patients with a history of idiopathic TTP functioning normally in their activities of daily living were recruited from existing patient cohorts at both the Ohio State University (n 5 12) (Columbus) and the University College London Hospitals (n 5 15) (London, UK). Nine of 23 (39%) of the MRI studies were abnormal; 17/27 (63%) patients demonstrated neurocognitive impairment, particularly in tests of visual learning and memory. Health-related quality of life scores were also significantly lower than age- and gender-matched US norms for both the composite mental component score and physical component score. These data suggest that the prevalence of neurologic findings in TTP patients in remission is quite high and is largely undetected by routine clinical evaluations. Further longitudinal study will be required to define the risk for neurologic injury and the long-term prognosis in patients previously diagnosed with TTP.

Preference-Based Quality of Life of End-Stage Ankle Arthritis Treated with Arthroplasty or Arthrodesis

Health state values, or "utilities,'' are an important preference-based measure of quality of life used by health economists. This study describes the utilities reported by a multicenter cohort of subjects with end-stage ankle arthritis treated with ankle arthrodesis or total ankle arthroplasty. Subjects with end-stage ankle arthritis were enrolled in a multicenter prospective cohort study. All subjects received either ankle arthrodesis or total ankle arthroplasty. Participants completed baseline SF-36 outcome evaluations preoperatively and at 1-year followup. Preference-based quality of life was assessed using health state values (HSVs) derived from the SF-36 (SF-6D transformation). 107 subjects were included. The mean baseline SF-6D health state value for the TAA group was 0.67 (95% CI 0.64 to 0.69) and 0.66 (95% CI 0.63 to 0.68) for the arthrodesis group. At 1-year followup, the mean reported health state value was 0.73 (95% CI 0.71 to 0.76) for the total ankle arthroplasty group and 0.73 (95% CI 0.70 to 0.76) for the ankle arthrodesis group. The 1-year followup results approach age- and gender-matched US population norms. Health state values poorly correlated with age, however, significant differences between genders were detected. These data demonstrate an improvement in preference-based quality of life following ankle arthroplasty or arthrodesis. The results also provide necessary data that can be used in future cost-effectiveness analyses.

Milnacipran improves health-related quality of life in patients with fibromyalgia (FM): results from a pivotal phase III randomized controlled trial

Fibromyalgia (FM) is associated with multiple impairments. A pivotal milnacipran clinical trial was analyzed for impact on SF-36 domains. Patients received milnacipran 100 mg/day, 200 mg/day, or placebo for 15 weeks (N = 1196). Health-related quality of life (HRQOL) improvements were evaluated using SF-36 Physical Component Summary (PCS), Mental Component Summary (MCS), and individual domain scores at each visit. Baseline PCS scores were found to be approximately 2 standard deviations (SDs) lower than age- and gender-matched US norms (17.6-18.1 point decrements). Baseline MCS scores reflected less impairment (7.1-9.3 point decrements; within 1 SD of norms). Individual domain scores with the greatest baseline impairments were vitality, bodily pain, role physical, and physical functioning. At endpoint, all groups achieved clinically meaningful improvements (≥MCID of 2.5-5.0 points) in PCS scores, with values approaching 1 SD of norms. Least square mean improvements in PCS scores at Week 15 were observed in 100 and 200 mg/day milnacipran-treated patients vs placebo (5.14 and 4.46 vs 3.28, respectively), with significant improvement observed with 100 mg/day (P < .01). Significant improvements >MCID of 5-10 points were evident in physical functioning and bodily pain in milnacipran-treated patients versus placebo (100 mg/day, P < .001; 200 mg/day, P < .01). Endpoint MCS scores approached norms of 50: 46.9 (milnacipran 100 mg/day) and 47.3 (milnacipran 200 mg/day) vs 46.1 (placebo), with significantly greater improvements in patients treated with milnacipran 200 mg/day (P < .05 vs placebo). Endpoint improvements greater than the MCID and significantly greater than placebo were evident with milnacipran 200 mg/day in role emotional (P < .05) and mental health (P < .05) domains; vitality domain scores were significantly improved with milnacipran 100 mg/day versus placebo (P < .01). Treatment with milnacipran resulted in SF-36 domain and MCS scores which approached age- and gender-matched US norms, despite large and clinically significant decrements at baseline. (Supported by Forest Laboratories, Inc. and Cypress Bioscience, Inc.)

Health-related quality of life in veterans with prevalent total knee arthroplasty and total hip arthroplasty.

To study the HRQOL in veterans with prevalent total knee arthroplasty (TKA) or total hip arthroplasty (THA) and compare them with age- and gender-matched US population and control veteran population without these procedures. A cohort study and cross-sectional survey on veterans obtained demographics and HRQOL with Short-Form 36 for veterans (SF-36V). Veterans were categorized into: primary TKA; primary THA; combination group (>/=1 primary and/or any revision TKA/THA); and control population (no THA/TKA). Multivariable regression compared the physical and mental component summary scores (PCS and MCS scores, respectively) in each group. Response rate was 58% (40 508/70 334): 531 with TKA, 254 with THA, 461 constituted the combination and 39 262, the control group. Mean PCS scores in veterans with THA, TKA, and combination group were 2 s.d. lower than the US mean (29.5 +/- 0.8; 30.1 +/- 1.1 and 27.1 +/- 0.8). MCS scores were similar to the US mean (47.3 +/- 0.9; 49.1 +/- 1.2 and 45.6 +/- 0.9). Compared with controls, significantly more veterans in TKA, THA or combination groups had multivariable-adjusted PCS </= 30 (55, 64, 71 and 76%; P < 0.0001); similar proportion had MCS </= 30 (15, 12, 8 and 16%; P = 0.29); and mean scores on SF-36 physical domains (P </= 0.0011), but not mental/emotional domains (P >/= 0.01) were statistically and clinically lower. Profound physical HRQOL deficits exist in veterans with TKA/THA and in combination group compared with age- and gender-matched general US population and with veteran controls. In these groups, these deficits are not attributable to differences in sociodemographics, comorbidity and healthcare access/utilization. Arthroplasty status may be a surrogate for poorer HRQOL and worse outcomes. Future studies are indicated to determine HRQOL deficit causes and interventions to improve HRQOL in patients with arthroplasty.

High prevalence of metabolic syndrome after allogeneic hematopoietic cell transplantation

We conducted a cross-sectional study to estimate the prevalence of metabolic syndrome, a clustering of risk factors associated with cardiovascular disease, among 86 adults who had allogeneic hematopoietic-cell transplant (HCT) as compared with 258 age- and gender-matched US population controls selected from the 2005-2006 National Health and Nutrition Examination Survey database. The median age at study enrollment was 50 years (range, 21-71), and patients were at a median of 3 years (range, 1-21) from HCT. The prevalence of metabolic syndrome was 49% (95% confidence intervals (CI), 38-60%) among HCT recipients, a 2.2-fold (95% CI, 1.3-3.6, P=0.002) increase compared with controls. The prevalence rates of elevated blood pressure and hypertriglyceridemia were significantly higher among HCT recipients than among controls, but the prevalence rates of abdominal obesity, elevated blood glucose and low high-density lipoprotein cholesterol were not. HCT survivors with metabolic syndrome were more likely to have microalbuminuria (43 vs 10%) and elevated creatinine (31 vs 11%). No patient, donor or transplant characteristics were associated with the diagnosis of metabolic syndrome. We conclude that metabolic syndrome occurs frequently among allogeneic HCT survivors who are seen by transplant physicians. Approaches to screening, prevention and management of metabolic syndrome should be developed for HCT recipients.

A comparison study of early non-psychotic deviant behavior in Afrikaner and US patients with schizophrenia or schizoaffective disorder

In a previous study early non-psychotic deviant behaviors in US adult schizophrenic patients recruited for a large-scale genetic study were examined ( Psychiatry Research, 101, 101). Early deviance characterized a distinct subgroup of patients at rates that were consistent with earlier reports. In addition, specific early non-psychotic deviant behaviors were meaningfully associated with later disease outcomes. In the present study, we examined the demographic, syndrome course, symptom and early deviant behavior history of 109 Afrikaner probands who met criteria for DSM schizophrenia or schizoaffective disorder, and compared them to 109 age- and gender-matched US probands. Consistent with past findings, 68% of Afrikaner probands, as compared to 67% of age- and gender-matched US probands, reported one or more forms of early non-psychotic deviance, including poor socialization, extreme fears/chronic sadness, and/or attention/learning impairment. The remaining 32 and 33% of probands, respectively, were without behavioral deviance until the onset of schizophrenia or schizoaffective disorder. The frequency and distribution of individual deviant behaviors were strikingly consistent between the samples. However, logistic regression analyses revealed different patterns of associations between the early deviant behaviors manifested and disease outcome. Afrikaner participants with early fears/chronic sadness were 3 times more likely to attempt suicide, while among US participants, this form of early deviance conferred 3.5 times more risk for later schizoaffective disorder, and 3 times greater likelihood of later sensory (tactile and/or olfactory) hallucinations. Afrikaner participants with attention/learning impairment were 2.5 times more likely to experience later auditory hallucinations, while US participants with these early difficulties were 3 times more likely to experience thought disorder. We concluded that early non-psychotic childhood deviance in this independently collected Afrikaner population distinguished a distinct subtype of patients and that the forms of early deviance manifested were meaningfully linked to later disease outcome. Possible reasons for the association pattern differences in these two populations are considered.