Diagnosing ventilator-associated pneumonia (VAP) in UK NHS ICUs: the perceived value and role of a novel optical technology.

BACKGROUND: Diagnosing ventilator-associated pneumonia (VAP) in an intensive care unit (ICU) is a complex process. Our aim was to collect, evaluate and represent the information relating to current clinical practice for the diagnosis of VAP in UK NHS ICUs, and to explore the potential value and role of a novel diagnostic for VAP, which uses optical molecular alveoscopy to visualise the alveolar space. METHODS: Qualitative study performing semi-structured interviews with clinical experts. Interviews were recorded, transcribed, and thematically analysed. A flow diagram of the VAP patient pathway was elicited and validated with the expert interviewees. Fourteen clinicians were interviewed from a range of UK NHS hospitals: 12 ICU consultants, 1 professor of respiratory medicine and 1 professor of critical care. RESULTS: Five themes were identified, relating to [1] current practice for the diagnosis of VAP, [2] current clinical need in VAP diagnostics, [3] the potential value and role of the technology, [4] the barriers to adoption and [5] the evidence requirements for the technology, to help facilitate a successful adoption. These themes indicated that diagnosis of VAP is extremely difficult, as is the decision to stop antibiotic treatment. The analysis revealed that there is a clinical need for a diagnostic that provides an accurate and timely diagnosis of the causative pathogen, without the long delays associated with return of culture results, and which is not dangerous to the patient. It was determined that the technology would satisfy important aspects of this clinical need for diagnosing VAP (and pneumonia, more generally), but would require further evidence on safety and efficacy in the patient population to facilitate adoption. CONCLUSIONS: Care pathway analysis performed in this study was deemed accurate and representative of current practice for diagnosing VAP in a UK ICU as determined by relevant clinical experts, and explored the value and role of a novel diagnostic, which uses optical technology, and could streamline the diagnostic pathway for VAP and other pneumonias.

Patient assessment of lower urinary tract symptoms using the international prostate symptom score following low-dose-rate prostate brachytherapy.

PURPOSE: To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. MATERIALS AND METHODS: Patients treated with prostate LDR between 2012 and 2019 (n=117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and ≥1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). RESULTS: 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy) with external beam radiation therapy. Twenty (18%) had baseline IPSS ≥15. Median IPSS scores were: baseline 6 (3-12; n=113), 1-month 17 (10-25; n=110), 6 months 12 (7-18; n=77), 1 year 8 (5-14; n=52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS ≥15 group exhibited lower rates of CSC-12 (13% v. 57%, p=0.05) but not CSC-6 (55% v. 80%, p=0.12). CONCLUSIONS: We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS ≥15 compared to those with low baseline scores.

Ventilator-associated pneumonia surveillance using two methods.

BACKGROUND: Ventilator-associated pneumonia surveillance is used as a quality indicator due to concerns that some cases may be preventable and may contribute to mortality. Various surveillance criteria exist for the purposes of national reporting, but a large-scale direct comparison has not been conducted. METHODS: A prospective cohort study applied two routinely used surveillance criteria for ventilator-associated pneumonia from the European Centre for Disease Control and the American Centers for Disease Control to all patients admitted to two large general intensive care units. Diagnostic rates and concordance amongst diagnostic events were compared. FINDINGS: A total of 713 at-risk patients were identified during the study period. The European surveillance algorithm returned a rate of 4.6 cases of ventilator-associated pneumonia per 1000 ventilation days (95% confidence interval 3.1-6.6) and the American surveillance system a rate of 5.4 (3.8-7.5). The concordance between diagnostic events was poor (Cohen's Kappa 0.127 (-0.003 to 0.256)). CONCLUSIONS: The algorithms yield similar rates, but the lack of event concordance reveals the absence of inter-algorithm agreement for diagnosing ventilator-associated pneumonia, potentially undermining surveillance as an indicator of care quality.

Ballistic and snake photon imaging for locating optical endomicroscopy fibres.

We demonstrate determination of the location of the distal-end of a fibre-optic device deep in tissue through the imaging of ballistic and snake photons using a time resolved single-photon detector array. The fibre was imaged with centimetre resolution, within clinically relevant settings and models. This technique can overcome the limitations imposed by tissue scattering in optically determining the in vivo location of fibre-optic medical instruments.

Endoscopic sensing of alveolar pH.

Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-to-fiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

AIMS/HYPOTHESIS: Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. METHODS: A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. RESULTS: Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. CONCLUSIONS/INTERPRETATION: Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. TRIAL REGISTRATION: ClincalTrials.gov: NCT00000620. FUNDING: The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Long-term safety of growth hormone replacement after CNS irradiation.

CONTEXT: Radiotherapy is a central component in the treatment of many brain tumors, but long-term sequelae include GH deficiency and increased risk of secondary neoplasms. It is unclear whether replacement therapy with GH (GHRT) further increases this risk. OBJECTIVE: The objective of the study was to assess the effect of GHRT on the incidence of secondary tumors and tumor recurrence after cranial irradiation. DESIGN AND SETTING: We conducted a retrospective matched-pairs analysis of previously irradiated patients, with and without GHRT, attending a tertiary center between 1994 and 2009. PATIENTS: We reviewed the records for all patients undergoing GHRT at our institution over the study period. PATIENTS were included if they had received cranial irradiation, GHRT for at least 12 months, and records of serial magnetic resonance imaging data and data for dose and fractionation of irradiation were available. GH-naïve control patients were selected from a radiotherapy database of patients attending the same hospital. PATIENTS were matched for date of radiotherapy, age, site of primary diagnosis, radiation dose, and fractionation. MAIN OUTCOME MEASURE: The primary outcome measure was risk of tumor recurrence or secondary tumor. RESULTS: Matched controls were identified for 110 GH-treated patients. Median follow-up was 14.5 yr. No significant differences were apparent in the number of tumor recurrences (six vs. eight, GHRT vs. control group) or secondary tumors (five vs. three, respectively) between groups. CONCLUSIONS: Our study demonstrates no increased risk for recurrent or secondary neoplasms in patients receiving GHRT, thus supporting a high safety profile of GHRT after central nervous system irradiation.

Electrical activity of caudal neurosecretory neurons in seawater- and freshwater-adapted flounder: responses to cholinergic agonists.

The caudal neurosecretory system (CNSS) of the euryhaline flounder is involved in osmoregulatory responses underlying adaptation to seawater and freshwater. This study compared electrophysiological activity and responses to cholinergic agonists in the neuroendocrine Dahlgren cells in an in vitro preparation taken from fully seawater- (SWA) or freshwater-adapted (FWA) fish. Resting membrane and action potential parameters showed few differences between SWA and FWA cells. The hyperpolarisation-activated sag potential and depolarising afterpotential were present under both conditions; however, amplitude of the latter was significantly greater in SWA cells. The proportions of cells within the population exhibiting different firing patterns were similar in both adaptation states. However, bursting parameters were more variable in FWA cells, suggesting that bursting activity was less robust. The muscarinic agonist, oxotremorine, was largely inhibitory in Dahlgren cells, but increased activity in a non-Dahlgren cell population, alpha neurons. Nicotine promoted bursting activity in SWA Dahlgren cells, whereas it inhibited over half of FWA cells.

Etiologic factors associated with anterior knee pain in distance runners.

PURPOSE: The objectives of this study were 1) to examine the differences between a noninjured (C) cohort of runners (N = 70) and runners afflicted with anterior knee pain (AKP) according to selected training, anthropometric, rearfoot motion, ground reaction force, and muscular strength and endurance variables; 2) to explore multivariate relationships among these measures in the well and injured groups; and 3) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospective clinical study. METHODS: High speed videography (200 frames x s(-1)), a force platform (500 Hz), and a Cybex II+ isokinetic dynamometer were used to assess rearfoot motion, ground reaction forces, and knee muscular strength and endurance, respectively. A linear discriminant function was performed on each of the five categories of variables and revealed 19 significant (P < or = 0.05) predictors. These variables were then combined and a final discriminant function analysis was performed. RESULTS: Pronation through the first 10% of stance, arch index, shoe mileage, and extension peak torque were the best overall (P < or = 0.05) predictors. The AKP group had smaller mean values on all four significant predictors. CONCLUSION: With the exception of shoe mileage, which is likely a response to rather than a risk factor for AKP, these results should prove useful to clinicians in identifying runners at risk for anterior knee pain.

Factors related to sleep disturbance in older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis.

OBJECTIVES: To describe the types and frequencies of sleep complaints and the biopsychosocial factors associated with sleep disturbance in a large community sample of older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis (OA). DESIGN: Baseline analyses of an observational prospective study. SETTING AND PARTICIPANTS: Participants were 429 men and women aged 65 years and older experiencing knee pain or knee pain with radiographic evidence of OA enrolled in the Observational Arthritis Study in Seniors (OASIS). MEASUREMENTS: Demographic variables (age, gender, ethnicity, education), health (X-rays of knee rated for OA severity, medical conditions, medication use, smoking status, body mass index, self-rated health), physical functioning (self-rated physical functioning, physical performance), knee pain, and psychosocial functioning (social support, depression) were measured. RESULTS: Problems with sleep onset, sleep maintenance, and early morning awakenings occurred at least weekly among 31%, 81%, and 51% of participants, respectively. Bivariate correlates of greater sleep disturbance in those with OA were less education, cardiovascular disease, more arthritic joints, poorer self-rated health, poorer physical functioning, poorer physical performance, knee pain, depression, and less social support. In regression analyses, each set of variables representing the domains of health, physical functioning, pain, and psychosocial functioning contributed to the prediction of sleep disturbance beyond the demographic set. Finally, in a simultaneous model, white race (trend, P = .06), poorer self-rated health, poorer physical functioning, and depressive symptoms were predictive of sleep disturbance. CONCLUSIONS: Sleep disturbance is common in older adults experiencing knee pain or knee pain with radiographic evidence of OA and is best understood through the consideration of demographic, physical health, physical functioning, pain, and psychosocial variables. Interventions that take into account the multidetermined nature of sleep disturbance in knee pain or knee OA are most likely to be successful.

Renal duplex sonography: main renal artery versus hilar analysis.

OBJECTIVE: The purpose of this study was to compare the accuracy of main renal artery Doppler scanning interrogation and hilar analysis to diagnose hemodynamically significant renal artery disease. METHODS: From January 1998 to August 1999, 41 patients had renal duplex sonography with both main renal artery interrogation and hilar analysis followed by angiography. They form the basis of this review. The sample consisted of 24 men and 17 women, with a mean age of 68.9 +/- 10.2 years, who provided 80 kidneys for comparative analysis. Significant renal artery disease revealed through angiography was defined as >/= 60% diameter-reducing stenosis or occlusion. Peak systolic velocity (PSV) (in meters per second) and the presence of poststenotic turbulence (PST) were determined from main renal artery interrogation. Acceleration time (AT) (in milliseconds) was measured by means of hilar analysis. Significant renal artery stenosis was defined by a PSV of 2.0 m/s or more and a PST or an AT more than 100 ms. Sensitivity analyses of both PSV and AT were examined, and 95% CIs were computed. Receiver operating characteristic curves were used to estimate optimal values for PSV and AT. RESULTS: Angiography revealed hemodynamically significant fibromuscular dysplasia in 5 kidneys (4 patients), atherosclerotic stenosis >/= 60% in 48 kidneys (30 patients), and renal artery occlusion in 4 kidneys (4 patients). Kidneys with significant renal artery stenosis had a higher PSV (2.54 +/- 0.11 vs 1.28 +/- 0.08, P <.001) and AT (82.43 +/- 7.2 vs 30.0 +/- 2.8, P <.001) compared with those without stenosis. Compared with angiography, a PSV of 2.0 m/s or more and PST demonstrated a sensitivity of 91%, specificity of 96%, and overall accuracy of 92% for detection of significant renal artery stenosis. Two of five studies with false-negative results reflected diseased polar vessels. By contrast, AT of more than 100 ms had a sensitivity of 32%, specificity of 100%, and overall accuracy of 54%. Receiver operating characteristic curve analysis revealed a PSV of more than 1.8 m/s and an AT of 58 ms or greater as optimal values. With an AT of 58 ms or more, the sensitivity was 58%, and specificity was 96%, with an overall accuracy of 70%. There were no apparent associations between PSV or AT and type or location of renal artery lesion, serum creatinine level, or end-diastolic ratio. CONCLUSION: Main renal artery interrogation is an accurate screening test to detect significant stenosis or occlusion of the main renal artery. Hilar analysis alone does not provide sufficient sensitivity to be used as a sole screening study. Neither method detects the presence of renovascular disease associated with polar vessels.

Management of ischemic nephropathy: dialysis-free survival after surgical repair.

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.

Long-term exercise and its effect on balance in older, osteoarthritic adults: results from the Fitness, Arthritis, and Seniors Trial (FAST).

OBJECTIVES: To examine the effects of 18-month aerobic walking and strength training programs on static postural stability among older adults with knee osteoarthritis. DESIGN: Randomized, single-blind, clinical trial of therapeutic exercise. SETTING: Both center-based (university) and home-based. PARTICIPANTS: A cohort of 103 older adults (age = 60 years) with knee osteoarthritis who were participants in a large (n = 439) clinical trial and who were randomly assigned to undergo biomechanical testing. INTERVENTION: An 18-month center- (3 months) and home-based (15 months) therapeutic exercise program. The subjects were randomized to one of three treatment arms: (1) aerobic walking; (2) health education control; or (3) weight training. MEASUREMENTS: Force platform static balance measures of average length (Rm) of the center of pressure (COP), average velocity (Vel) of the COP, elliptical area (Ae) of the COP, and balance time (T). Measures were made under four conditions: eyes open, double- and single-leg stances and eyes closed, double- and single-leg stances. RESULTS: In the eyes closed, double-leg stance condition, both the aerobic and weight training groups demonstrated significantly better sway measures relative to the health education group. The aerobic group also demonstrated better balance in the eyes open, single-leg stance condition. CONCLUSIONS: Our results suggest that long-term weight training and aerobic walking programs significantly improve postural sway in older, osteoarthritic adults, thereby decreasing the likelihood of larger postural sway disturbances relative to a control group.

Etiologic factors associated with Achilles tendinitis in runners.

PURPOSE: The purpose of this study was to determine whether relationships exist between selected training, anthropometric, isokinetic muscular strength, and endurance, ground reaction force, and rearfoot movement variables in runners afflicted with Achilles tendinitis. METHODS: Specifically, we examined differences in selected measures between a noninjured cohort of runners (N = 58) and a cohort of injured runners with Achilles tendinitis (N = 31). Isokinetic, kinetic, and kinematic measures were collected using a Cybex II+ isokinetic dynamometer (Medway, MA), AMTI force plate (500 Hz), and Motion Analysis high-speed videography (200 Hz), respectively. Separate discriminant function analyses were performed on each of the five sets of variables to identify the factors that best discriminate between the injured and control groups. RESULTS: Years running, training pace, stretching habits (injured runners were less likely to incorporate stretching into their training routine), touchdown angle, plantar flexion peak torque at 180 degrees x s(-1) and arch index were found to be significant discriminators. CONCLUSION: A combined discriminant analysis using the above mentioned significant variables revealed that plantar flexion peak torque, touchdown angle, and years running were the strongest discriminators between runners afflicted with Achilles tendinitis and runners who had no history of overuse injury.

Surgery after failed percutaneous renal artery angioplasty.

PURPOSE: This retrospective review describes the surgical management of 51 patients after failed percutaneous renal artery angioplasty (F-PTRA). METHODS: From January 1987 through June 1998, 51 consecutive patients underwent surgical repair of either atherosclerotic (32 patients) or fibromuscular dysplastic (FMD; 19 patients) renovascular vascular disease after F-PTRA. These patients form the basis of this report. Surgical repair was performed for hypertension (29 patients with atherosclerosis: mean blood pressure, 205 +/- 34/110 +/- 23 mm Hg; 18 patients with FMD: mean blood pressure, 194 +/- 24/118 +/- 18 mm Hg) or ischemic nephropathy (20 patients with atherosclerosis: mean serum creatinine level, 2.0 +/- 0.8 mg/dL; three patients with FMD: mean serum creatinine level, 2.0 +/- 1.1 mg/dL). Emergency operation was required in four patients for acute renal artery thrombosis (one patient with atherosclerosis, one patient with FMD), renal artery rupture (one patient with atherosclerosis), or infected pseudoaneurysm (one patient with atherosclerosis). Operative management, blood pressure and renal function response to operation, and dialysis-free survival rate were examined and compared with 487 patients (441 patients with atherosclerosis, 46 patients with FMD) treated by operation alone. RESULTS: Among the patients with atherosclerotic renovascular disease, there were three postoperative deaths (9.4%) after repair for F-PTRA. Secondary operative repair was associated with emergent repair or nephrectomy in 16% of cases, while more extensive renal artery exposure and more complex operative management was required in 50% of patients with atherosclerosis and 65% of patients with FMD repaired electively. Among the 28 operative survivors with hypertension and atherosclerotic renovascular disease, blood pressure benefit after F-PTRA was significantly lower when compared with patients with atherosclerosis who underwent treatment with operation only (57% vs 89%; P <.001). However, blood pressure benefit in the 19 patients with FMD did not differ (89% vs 96%). Among the 28 patients with atherosclerosis, preoperative estimated glomerular filtration rate (EGFR) as compared with postoperative EGFR was significantly increased (47.4 +/- 4.2 mL/min/1.73m(2) vs 56. 6 +/- 5.1 mL/min/1.73m(2); P =.002). However, EGFR prior to PTRA was not significantly different from postoperative EGFR (51.6 +/- 3.4 mL/min/1.73m(2) vs 56.6 +/- 4.9 mL/min/1.73m(2); P =.121). As compared with patients with atherosclerosis who underwent treatment with operation alone, there was no difference in the dialysis-free survival rate. CONCLUSION: Operative repair after F-PTRA was altered in 59% of the patients with atherosclerosis and in 68% of patients with FMD. Blood pressure benefit for patients with FMD was unchanged after F-PTRA. However, the blood pressure benefit was significantly decreased among patients with atherosclerosis. Decreased EGFR after F-PTRA was recovered with operative renal artery repair. However, postoperative EGFR as compared with EGFR prior to PTRA was unchanged. Blood pressure and renal function response after F-PTRA for atherosclerotic renovascular disease warrants further study.

1996 Remington lecture: modeling multivariate longitudinal data that are incomplete.

PURPOSE: We describe the impact that missing data may have on model selection for longitudinal multivariate data. METHODS: Maximum likelihood was used to fit several models to ultrasonographic measurements from the Asymptomatic Carotid Artery Progression Study (ACAPS). Graphical techniques were used to examine evidence concerning the underlying missing data mechanisms associated with each model. RESULTS: Using statistical methodology that addressed missing data substantially increased the statistical efficiency of our analysis of ultrasonographic data. Only complex models that included segment-specific parameterizations for longitudinal correlations appeared to allow missing data to be assumed to occur at random. CONCLUSION: Ignoring the nature of missing data in conducting statistical analyses can have serious consequences when missingness is not rare. It may be necessary to fit models of high dimension with maximum likelihood techniques to address missing data appropriately, however these approaches may improve statistical efficiency.

Chronic renal artery occlusion: nephrectomy versus revascularization.

PURPOSE: The surgical management of chronic atherosclerotic renal artery occlusion (RA-OCC) was studied. METHODS: From January 1987 through December 1996, 397 consecutive patients were treated for atherosclerotic renal artery disease. Ninety-five hypertensive patients (mean blood pressure, 204 +/- 31/106 +/- 20 mm Hg; mean medications, 3.0 +/- 1.1 drugs) were treated for 100 RA-OCCs. Eighty-four (88%) patients had renal dysfunction, defined by serum creatinine levels >/=1.3 mg/dL (mean serum creatinine level, 2.8 +/- 2.0 mg/dL). Demographic characteristics, operative morbidity and mortality, blood pressure/renal function response, and postoperative decline in renal function were examined and compared with that of 302 patients treated for renal artery stenosis (RAS). RESULTS: After operation, there were 5 perioperative deaths (5.2%), 2 (2.8%) after revascularization and 3 (12%) after nephrectomy (P =.11), compared with 12 (4.0%) perioperative deaths in the RAS group (P =.59). After controlling for important covariates, estimated survival and blood pressure benefits did not differ between RA-OCC patients treated by nephrectomy or revascularization (P =.13; 87% vs 92%, P =.54). Excretory renal function was considered improved in 49% of 79 RA-OCC patients with renal dysfunction, including 9 patients removed from dialysis-dependence. Among patients treated for unilateral disease, revascularization for RA-OCC was associated with significant improvement in renal function (P <.01); however, nephrectomy alone did not increase renal function significantly. Improved renal function after operation was associated with a significant and independent increase in survival (P <.01) and dialysis-free survival (P <.01) among patients treated for RA-OCC. In addition, blood pressure benefit, renal function response, and estimated survival did not differ significantly after reconstruction for RA-OCC or RAS. CONCLUSION: Among hypertensive patients treated for RA-OCC, equivalent beneficial blood pressure response was observed after both revascularization and nephrectomy. In patients who underwent bilateral renal artery revascularization, the change in excretory renal function attributable to repair of RA-OCC cannot be defined. In patients treated for unilateral disease, however, improvement in function was observed only after revascularization. Moreover, improved renal function demonstrated a significant and independent association with improved survival. This experience supports renal revascularization in preference to nephrectomy for RA-OCC in select hypertensive patients when a normal distal artery is demonstrated at operation.

Isradipine in prediabetic hypertensive subjects.

OBJECTIVE: Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA1c) might have influenced the effects of the two agents on blood pressure control and CVD events. RESEARCH DESIGN AND METHODS: Inclusion criteria included men and women > or = 40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of > 90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5-5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5-25 mg twice a day) and followed in double-blind fashion for 3 years. RESULTS: Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA1c who also experienced greater blood pressure reductions during follow-up. CONCLUSIONS: The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.

Ten-year trends in cigarette smoking among young adults, 1986-1996: the CARDIA study. Coronary Artery Risk Development In Young Adults.

PURPOSE: To calculate ten-year smoking trends in a longitudinal cohort of young adults, and to characterize trends by race, sex, education, and birth cohort. METHODS: Data on cigarette smoking have been collected for ten years (1986-1996) from 5115 black and white men and women, aged 18-30 years, participating in the Coronary Artery Risk Development In Young Adults (CARDIA) study. Regression analysis adjusting for intra-person correlation over time and weighting for factors affecting follow-up was used to estimate change in smoking rates. RESULTS: Overall, smoking rates declined in white women (-0.50%/year, p < 0.001) and white men (-0.24%/year, p = 0.03). Rates remained stable in black women and increased in black men (0.37%/year, p = 0.01). Declining rates were generally observed in white women of all educational levels and birth cohorts and in several subgroups of white men. Increasing rates among black men could be attributed primarily to increasing rates in the youngest birth cohort. Among black men and women, prevalence of smoking in 1986 was considerably lower in the youngest birth cohort compared to the oldest; however, the increasing rates of change in smoking rates observed among the youngest birth cohorts (and decreasing rates in the oldest) lessened the disparity in prevalence rates across birth cohorts by 1996. Smoking initiation rates were highest among black men; cessation rates were highest among white women. CONCLUSIONS: These findings confirm that declines in smoking prevalence are not occurring across all groups, and reveal populations in special need of targeted interventions, particularly young black men.

Renal artery repair: consequence of operative failures.

OBJECTIVE: This report examines the blood pressure and renal function response in 20 consecutive patients after secondary renal revascularization following failed operative repair. SUMMARY BACKGROUND DATA: Most reports describing operative failure of renal artery (RA) repair emphasize the technical aspects of redo RA reconstruction and the immediate blood-pressure response to secondary operation. This report examines the eventual renal function and estimated survival after secondary intervention. METHODS: Primary methods of RA reconstruction, primary blood pressure and renal function responses, and causes of failed RA repair were defined for 20 patients requiring reoperation for recurrent hypertension or renal insufficiency. These parameters were compared with secondary procedures and eventual blood pressure and renal function response. The eventual outcome for these 20 patients was compared with 514 patients managed by primary renal revascularization during the same period. RESULTS: Failure of primary RA repair correlated with complex fibromuscular dysplasia requiring branch ex vivo reconstruction (p = 0.020). RA thrombosis frequently required nephrectomy (83%), whereas RA stenosis was successfully reconstructed (91 %; p = 0.001). Primary and secondary blood-pressure responses were equivalent (94% vs. 95% cured or improved); however, primary and eventual renal function responses differed significantly (p = 0.015), with seven patients dialysis-dependent on follow-up. Eventual dialysis dependence was associated with preoperative azotemia (p = 0.022), bilateral failure of primary RA repair (p = 0.007), and an increased risk of follow-up death (p = 0.002). Considering all 534 patients, failed RA repair demonstrated a significant and independent association with eventual dialysis dependence and decreased dialysis-free survival. CONCLUSIONS: Contemporary rates of reoperation after surgical RA repair are low. In properly selected patients, beneficial blood-pressure response is reliably observed after both primary and secondary operative procedures. However, secondary procedures are associated with a significant and independent risk of eventual dialysis dependence.