OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. PATIENTS AND METHODS: Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. RESULTS: Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). CONCLUSIONS: Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. CLINICAL TRIAL REGISTRATION: Clinical trials.gov identifier: NCT02258659.

Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer.

BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678.

Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades.

BACKGROUND: Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials. PATIENTS AND METHODS: We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time. RESULTS: Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38). CONCLUSIONS: Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC.

Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects.

Estimation of renal cell carcinoma treatment effects from disease progression modeling.

To improve future drug development efficiency in renal cell carcinoma (RCC), a disease-progression model was developed with longitudinal tumor size data from a phase III trial of sorafenib in RCC. The best-fit model was externally evaluated on 145 placebo-treated patients in a phase III trial of pazopanib; the model incorporated baseline tumor size, a linear disease-progression component, and an exponential drug effect (DE) parameter. With the model-estimated effect of sorafenib on RCC growth, we calculated the power of randomized phase II trials between sorafenib and hypothetical comparators over a range of effects. A hypothetical comparator with 80% greater DE than sorafenib would have 82% power (one-sided α = 0.1) with 50 patients per arm. Model-based quantitation of treatment effect with computed tomography (CT) imaging offers a scaffold on which to develop new, more efficient, phase II trial end points and analytic strategies for RCC.

Radiographic texture analysis of densitometer-generated calcaneus images differentiates postmenopausal women with and without fractures.

INTRODUCTION: Bone fragility is determined by bone mass, measured as bone mineral density (BMD), and by trabecular structure, which cannot be easily measured using currently available noninvasive methods. In previous studies, radiographic texture analysis (RTA) performed on the radiographic images of the spine, proximal femur, and os calcis differentiated subjects with and without osteoporotic fractures. The present cross-sectional study was undertaken to determine whether such differentiation could also be made using high-resolution os calcis images obtained on a peripheral densitometer. METHODS: In 170 postmenopausal women (42 with and 128 without prevalent vertebral fractures) who had no secondary causes of osteoporosis and were not receiving treatment for osteoporosis, BMD of the lumbar spine, proximal femur, and os calcis was measured using dual energy x-ray absorptiometry. Vertebral fractures were diagnosed on densitometric spine images. RTA, including Fourier-based and fractal analyses, was performed on densitometric images of os calcis. RESULTS: BMD at all three sites and all texture features was significantly different in subjects with and without fractures, with the most significant differences observed for the femoral neck and total hip measurements and for the RTA feature Minkowski fractal (p<0.001). In univariate logistic regression analysis, Minkowski fractal predicted the presence of vertebral fractures as well as femoral neck BMD (p<0.001). In multivariate logistic regression analysis, both femoral neck BMD and Minkowski fractal yielded significant predictive effects (p=0.001), and when age was added to the model, the effect of RTA remained significant (p=0.002), suggesting that RTA reflects an aspect of bone fragility that is not captured by age or BMD. Finally, when RTA was compared in 42 fracture patients and 42 nonfracture patients matched for age and BMD, the RTA features were significantly different between the groups (p=0.003 to p=0.04), although BMD and age were not. CONCLUSION: This study suggests that RTA of densitometer-generated calcaneus images provides an estimate of bone fragility independent of and complementary to BMD measurement and age.

Factors associated with older patients' satisfaction with care in an inner-city emergency department.

STUDY OBJECTIVES: We sought to assess older patients' satisfaction with care in the emergency department and to identify factors associated with global satisfaction with care. METHODS: We performed a prospective cohort study of 778 patients 65 years of age and older presenting to an urban academic ED between 1995 and 1996, of whom 79% were black and 63% were female. A baseline survey at presentation to the ED asked for demographic information, medical history, and health-related quality of life information. A follow-up satisfaction survey asked patients to rate the care they received in the ED on a 5-point Likert scale (1=excellent, 5=poor). Overall satisfaction with care, dichotomized into responses of "excellent" versus all others, was the primary dependent variable in our bivariate analyses. RESULTS: Of respondents, 40% rated their ED care as "excellent." Variables significantly correlated with high satisfaction include having the perception of time spent in the ED as not "too long," having the emergency physicians and nurses clearly answer patients' questions, having a relationship of trust with an ED staff member, being told why tests were done, feeling involved in decisions about care as much as they wanted, having pain addressed fully, having a perception of greater health status, and having fewer comorbid conditions at the time of the ED visit. Results may be applicable only to urban academic EDs and may be limited by time elapsed between ED visits and follow-up surveys. CONCLUSION: To improve quality of care for older adults in the ED, physicians should be more attentive to older patients' concerns and questions, recognize and aggressively treat pain, and reduce the patients' perception of a long waiting time.

Early revisit, hospitalization, or death among older persons discharged from the ED.

The purpose of this study to determine predictors of revisit, hospital admission, or death among older patients discharged from the emergency department (ED). We performed a prospective study of patients aged 65 or older in an urban ED. The primary outcomes were ED revisit, hospital admission, or death 30 or 90 days after discharge from an index ED visit. Of the 463 eligible patients, 75 (16%) experienced ED revisit, hospitalization, or death within 30 days, and 125 (27%) within 90 days. In multivariate proportional hazards models, physical functioning and mental health in the lowest tertile, and lack of supplemental insurance predicted revisit, hospitalization, or death within 30 days after ED discharge. Poor physical functioning, missing mini-mental state examination, comorbidity, and ambulance transport to the initial ED visit predicted 90-day outcome. Problems with physical functioning, mental health and supplemental insurance are potentially remediable precursors of early morbidity among older patients after ED discharge. Future research should examine whether addressing these issues among the elderly population will lessen ED return visits, hospitalization, and mortality.

A benzodiazepine hypnotic facilitates adaptation of circadian rhythms and sleep-wake homeostasis to an eight hour delay shift simulating westward jet lag.

STUDY OBJECTIVES: To determine whether appropriately timed administration of a short-acting benzodiazepine hypnotic, which has proven effective in an animal model of jet lag, also facilitates adaptation of circadian rhythmicity and sleep-wake homeostasis in a human model of jet lag. DESIGN: Subjects participated in two double-blind, placebo-controlled studies of adaptation to an 8-hr delay shift of sleep-wake and dark-light cycles simulating westward travel. Each 9-day laboratory study began with a 3-day habituation period followed by a 24-hr study to obtain basal hormonal and sleep profiles (23:00-07:00). Subjects were then kept awake until 07:00 the next day and slept in darkness 07:00-15:00 for the next five 24-hr spans post-shift. SETTING: N/A. PARTICIPANTS: 6 normal, healthy men 24-31 years of age. INTERVENTIONS: Oral Triazolam (0.5 mg) or placebo given at 04:00 before the first shifted sleep/dark period (3 hours before bedtime) and at 07:00 (at bedtime) on days 2-5 post-shift. MEASUREMENTS AND RESULTS: Sleep recordings and 24-hr cortisol and growth hormone profiles were obtained at baseline and on the first, third, and fifth days post-shift. Global measures of treatment efficacy were calculated for multiple endpoints representing circadian rhythmicity and sleep-wake homeostasis. With placebo, the shift induced disturbances of sleep and hormonal secretion, and a gradual re-entrainment of circadian rhythmicity. Triazolam significantly facilitated adaptation by accelerating re-entrainment of circadian rhythms (chronobiotic effect) and normalizing markers of sleep/wake homeostasis (hypnotic effect). CONCLUSIONS: Appropriately timed administration of a benzodiazepine hypnotic appears to facilitate the adaptation of both circadian rhythmicity and sleep-wake homeostasis to a shifted dark/sleep cycle. Compounds with combined chronobiotic/hypnotic properties may be useful in conditions of jet lag or night work.

Quality of diabetes care in community health centers.

OBJECTIVES: This study assessed the quality of diabetes care in community health centers. METHODS: In 55 midwestern community health centers, we reviewed the charts of 2865 diabetic adults for American Diabetes Association measures of quality. RESULTS: On average, 70% of the patients in each community health center had measurements of glycosylated hemoglobin, 26% had dilated eye examinations, 66% had diet intervention, and 51% received foot care. The average glycosylated hemoglobin value per community health center was 8.6%. Practice guidelines were independently associated with higher quality of care. CONCLUSIONS: Rates of adherence to process measures of quality were relatively low among community health centers, compared with the targets established by the American Diabetes Association.

Appropriateness of medication selection for older persons in an urban academic emergency department.

OBJECTIVES: To determine the frequency of potentially inappropriate medication selection for older persons presenting to the ED, the most common problematic drugs, risk factors for suboptimal medication selection, and whether use of these medications is associated with worse outcomes. METHODS: The authors performed a prospective cohort study of 898 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Seventy-nine percent of the patients were African-American and 43% did not graduate from high school. Potentially inappropriate medications and adverse drug-disease interactions were identified using the 1997 Beers explicit criteria for elders. During the three months after the initial visit, revisits to the ED or hospital, death, and changes in health-related quality of life were analyzed as measured by validated questions adapted from the Medical Outcomes Study. RESULTS: Upon presentation, 10.6% of the patients were taking a potentially inappropriate medication, 3.6% were given one in the ED, and 5.6% were prescribed one upon discharge from the ED. The most frequently prescribed potentially inappropriate medications in the ED were diphenhydramine, indomethacin, meperidine, and cyclobenzaprine. Emergency physicians added potentially inappropriate medications most often to patients with discharge diagnoses of musculoskeletal disorder, back pain, gout, and allergy or urticaria. Potentially adverse drug-disease interactions were relatively uncommon at presentation (5.2%), in the ED (0.6%), and on discharge from the ED (1.2%). Potentially inappropriate medications and adverse drug-disease interactions prescribed in the ED were not associated with higher rates of revisit to the ED, hospitalization, or death, but were correlated with worse physical function and pain. However, confidence intervals were wide for analyses of revisits and death. CONCLUSIONS: Suboptimal medication selection was fairly common and was associated with worse patient-reported health-related quality of life.

Older patients' health-related quality of life around an episode of emergency illness.

STUDY OBJECTIVES: We sought to describe older patients' health-related quality of life during a 4-month period surrounding a visit to the emergency department and to identify factors associated with less recovery. METHODS: We prospectively studied 983 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Eighty percent of the patients were African American, and 63% were women. The primary outcome measures were the Katz Index of Activities of Daily Living and revised validated questions from the Medical Outcomes Study Health Survey at 1 month before the ED visit, the time of the ED visit, and 2-week and 3-month follow-up periods. RESULTS: In general, patients worsened markedly during the illness and then improved, although not to baseline levels. After adjustment for demographic and social factors, the most consistently powerful predictors of poor recovery were more deficiencies in activities of daily living at baseline, reports of needing more help with everyday tasks, increasing Charlson Comorbidity Index scores, and requiring a proxy for the initial survey. CONCLUSION: Emergency physicians and primary care physicians should consider inquiring about functional status and the adequacy of help at home in addition to comorbid conditions for their acutely ill older patients to target those at greatest risk for poor recovery. Future work needs to test interventions that may improve the health-related quality of life of these vulnerable patients.

Dormancy of mammary carcinoma after mastectomy.

BACKGROUND: The longest interval between primary treatment of breast cancer and tumor recurrence, i.e., the limit of breast cancer dormancy, defines the appropriate length of follow-up, the effectiveness of treatment, and curability (no excess mortality risk for patients relative to the general population) for the disease. To determine this limit, we analyzed long-term follow-up data from patients who underwent a radical mastectomy during a four-decade period at the University of Chicago Hospitals. METHODS: For 1547 patients operated on during the period from 1945 through mid-1987, the number of recurrences and deaths occurring within each postoperative year were tabulated, and the hazard rate for first recurrence or death from breast cancer was estimated by use of the actuarial method. The excess mortality rate was calculated for successive 5-year intervals, beginning at the time of mastectomy, by use of U.S. life tables and matching on the basis of age, race, and sex. RESULTS: Most recurrences occurred within the first 10 years after mastectomy. Recurrences were rare after 20 years; only one recurrence was reported among 192 patients followed for 26-45 years. Patients who had a recurrence within 5 years following mastectomy had shorter subsequent survival times than those whose recurrence appeared after 5 years (two-sided P = .0001). The excess death rate increased with pathologic stage of the primary tumor. Overall, there was evidence of excess mortality up to 20 years postsurgery (two-sided P = .009). CONCLUSIONS: The limit of breast cancer dormancy in this patient population appears to be between 20 and 25 years. After this time, recurrences were rare, and the mortality rate was no longer statistically significantly different from that of the general population. Patients surviving to this time without evidence of recurrence or contralateral breast cancer are probably cured.

Recurrent miscarriage (REMIS) study: how should data from women who do not become pregnant be handled?

The Recurrent Miscarriage (REMIS) study is a double-blind, multicenter, randomized clinical trial designed to evaluate the efficacy of immunization with paternal leukocytes in the prevention of miscarriages in women who have had three or more unexplained pregnancy losses. Women entering the study are immunized with their husband's leukocytes or with a saline control before they become pregnant. After becoming pregnant, they receive weekly ultrasound examinations and psychological support during the first trimester and are followed until a successful delivery or a miscarriage occurs. The primary analysis for the study will be an intent-to-treat analysis in which we shall compare the proportion of successes in the two groups, defining a "success" as a pregnancy achieved within 12 months of randomization that results in a viable offspring. We shall count both miscarriages and nonpregnancies as failures, owing to the possibility of very early losses prior to the detection of pregnancy. In a secondary analysis, we shall exclude women who do not become pregnant within the alloted 12 month period. We compared the test size and power of these two approaches under various configurations for the true rates of nonpregnancy, miscarriage, and delivery in the two groups. Although the analysis excluding nonpregnant women achieves greater power for alternatives in which pregnancy rates are equal and live birth rates higher in the treated group, the rejection rate is not adequately controlled when pregnancy rates differ but live birth rates are unaffected by treatment. It can also lead to a reduction in power if the treatment prevents early as well as later losses. We conclude that the intent-to-treat analysis should remain the primary analysis for the trial.

Transmission disequilibrium of maternally-inherited CTLA-4 microsatellite alleles in idiopathic recurrent miscarriage.

To elucidate the mechanisms that facilitate tolerance at the maternal-fetal interface, we are investigating the role of genes that are involved in peripheral self-tolerance in couples with idiopathic recurrent miscarriage. CTLA-4 is a negative regulator of T-cell proliferation and has been associated with human autoimmune disease. An AT(n) polymorphism in the 3'-untranslated region (UTR) of the human gene results in AT stretches that vary in length from 16 to 46 bp. We hypothesized that long stretches of AT repeats would result in mRNA instability, and reduced fetal survival in humans. We examined the transmission of AT(n) alleles in 60 couples with a history of > or = 3 unexplained spontaneous abortions to their 51liveborn children and 10 abortuses. The shorter allele was transmitted from heterozygous mothers to 26 of 35 liveborn children (chi2 = 8.3, P = 0.0040) and to three of nine aborted fetuses (chi2 = 1.0, P = 0.317). The shorter allele was transmitted from heterozygous fathers to 15 of 32 liveborn children (chi2 =0.12, P=0.726) and to five of eight aborted fetuses (chi2 = 0.5, P = 0.480). Furthermore, liveborn fetuses who inherited smaller alleles were more likely to represent the first successful pregnancy than liveborn fetuses who inherited larger maternal alleles (Pexact = 0.044) and fetuses of first pregnancies that inherited the smaller allele were significantly more likely to survive to term (Pexact = 0.0086). The preferential transmission of maternally-inherited shorter alleles to liveborn children, but random transmission of paternally-inherited alleles, suggests that CTLA-4 may be imprinted in humans and that this gene may play a role in inducing or maintaining tolerance at the maternal-fetal interface.

Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997.

Data compiled during the 1970s and early 1980s indicated that during these periods, membranous nephropathy was the most common cause of unexplained nephrotic syndrome in adults, followed in order of frequency by minimal-change nephropathy and focal segmental glomerulosclerosis (FSGS). However, we and others recently reported an increase in the incidence of FSGS over the past two decades, and the number of cases of FSGS diagnosed by renal biopsies in these centers now exceeds the number of cases of membranous nephropathy. Nonetheless, as a substantial fraction of patients with FSGS do not have the nephrotic syndrome, it remained unclear as to what extent the relative frequencies of FSGS and other glomerulopathies as causes of the nephrotic syndrome have changed over this time. To address this concern, we reviewed data from 1,000 adult native kidney biopsies performed between January 1976 and April 1979 and from 1,000 biopsies performed between January 1995 and January 1997, identified all cases with a full-blown nephrotic syndrome of unknown etiology at the time of biopsy, and compared the relative frequencies with which specific diseases were diagnosed in these latter cases between the two time intervals. The main findings of this study were that, first, during the 1976 to 1979 period, the relative frequencies of membranous (36%) and minimal-change (23%) nephropathies and of FSGS (15%) as causes of unexplained nephrotic syndrome were similar to those observed in previous studies during the 1970s and early 1980s. In contrast, from 1995 to 1997, FSGS was the most common cause of this syndrome, accounting for 35% of cases compared with 33% for membranous nephropathy. Second, during the 1995 to 1997 period, FSGS accounted for more than 50% of cases of unexplained nephrotic syndrome in black adults and for 67% of such cases in black adults younger than 45 years. Third, although the relative frequency of nephrotic syndrome due to FSGS was two to three times higher in black than in white patients during both study periods, the frequency of FSGS increased similarly among both racial groups from the earlier to the later period. Fourth, the frequency of minimal-change nephrotic syndrome decreased from the earlier to the later study period in both black and white adults. Fifth, the relative frequency of membranoproliferative glomerulonephritis as a cause of the nephrotic syndrome declined from the 1976 to 1979 period to the 1995 to 1997 period, whereas that of immunoglobulin A nephropathy appeared to increase; the latter accounted for 14% of cases of unexplained nephrotic syndrome in white adults during the latter study period. Finally, 10% of nephrotic adults older than 44 years had AL amyloid nephropathy; none of these patients had multiple myeloma or a known paraprotein at the time of renal biopsy.

Serum creatinine measurements in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

OBJECTIVES: To determine the usefulness of routine serum creatinine measurements in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to correlate these findings with patient age, symptom severity, and comorbid diseases. METHODS: We analyzed serum creatinine measurements in 246 consecutive men presenting for evaluation of voiding symptoms and BPH. Multiple logistic regression analysis was used to determine whether the International Prostate Symptom Score (IPSS), quality-of-life measure from the IPSS, patient age, or a history of diabetes mellitus or hypertension predicted abnormal creatinine levels. RESULTS: An elevated serum creatinine level was noted in 11% (26 of 245) of evaluable patients. Only a history of diabetes or hypertension predicted the presence of renal insufficiency. Among men with no history of comorbid disease, increasing age was significantly associated with the finding of an abnormal creatinine. Neither the overall symptom score nor the quality-of-life measure was significantly associated with the likelihood of detectable renal dysfunction. CONCLUSIONS: Medical renal disease secondary to diabetes or hypertension appears to be the most likely cause of elevated serum creatinine measurements in men with BPH and renal insufficiency. We were unable to identify subgroups of patients in whom the risk of renal dysfunction is sufficiently low to avoid routine serum creatinine measurements.