David F. Cruess

MULTICENTER PATIENT SELF-REPORTING QUESTIONNAIRE ON IMPOTENCE, INCONTINENCE AND STRICTURE AFTER RADICAL PROSTATECTOMY

PURPOSE We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Early-onset group B streptococcal sepsis: A current assessment

Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early-onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management.

Hospitalizations for fungal infections after renal transplantation in the United States

Abstract: Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post‐transplant, but only 22% by two months. In logistic regression analysis, end‐stage renal disease due to diabetes, duration of pre‐transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22–3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre‐transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.

Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.

Effect of Donor Factors on Early Graft Survival in Adult Cadaveric Renal Transplantation

Previous studies of the effect of donor factors on renal transplant outcomes have not tested the role of recipient body mass index, donor/recipient weight ratios and age matching, and other factors. We analyzed 20 309 adult (age 16 or older) recipients having solitary cadaveric renal transplants from adult donors from 1 July 1994 to 30 June 1998 in an historical cohort study (the 2000 United States Renal Data System) of death censored graft loss by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. The only independently significant findings in Cox Regression analysis were a high donor/recipient age ratio (≥ 1.10, e.g. a 55‐year‐old donor given to a recipient age 50 years or younger, adjusted hazard ratio (AHR) 3.22, 95% confidence interval (CI) 2.36–4.39) and African American donor kidneys (AHR 1.64, 95% CI, 1.24–2.17). African American recipients and older donors were not at independently increased risk of graft failure in this model. Among donor factors, older donor kidneys given to younger recipients and donor African American kidneys were independently associated with graft loss in recipients of cadaver kidneys. The task for the transplant community should be to find the best means for managing all donor organs without discouraging organ donation.

Hospitalizations for Cytomegalovirus Disease after Renal Transplantation in the United States

PURPOSE Risk factors, sites, and mortality of hospitalized cytomegalovirus (CMV) disease in renal transplant recipients have not been studied in a national population. METHODS Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1, 1994 to June 30, 1997 were analyzed in an historical cohort study of patients with a primary discharge diagnosis of CMV disease (ICD9 Code 078.5x). RESULTS Renal transplant recipients had an incidence density of hospitalized CMV disease of 1.26/100 person years, and 79% of hospitalizations for CMV disease occurred in the first six months post transplant. The leading manifestation of hospitalized infection was pneumonia (17%). In logistic regression analysis controlling for transplant era, pre-transplant dialysis > or = 6 months, maintenance mycophenolate mofetil (MMF) therapy, and allograft rejection, but not induction antibody therapy, were significantly associated with hospitalized CMV disease. Compared with recipients with negative CMV serology (R-) who had donor kidneys with negative CMV serology (D-), D+/R- had the highest risk of hospitalization for CMV disease [adjusted odds ratio (AOR) 5.19, 95% confidence interval (CI) 3.89-6.93] followed by D+/R+ recipients, whereas D-/R+ were not at significantly increased risk. In Cox Regression analysis the relative risk of death associated with hospitalized CMV disease was 1.32 (95% CI 1.02-1.71). CONCLUSIONS Even in modern era, renal transplant recipients were at high risk for hospitalizations for CMV disease, which were associated with decreased patient survival. Current prophylactic measures have apparently not reduced the high risk of D+/R- recipients. Prolonged pre-transplant dialysis and maintenance MMF should also be considered risk factors for hospitalized CMV infection, and prospective trials of prophylactic antiviral therapy should be performed in these subgroups.

Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression

Renal insufficiency has been identified as a risk factor for graft loss and death after renal transplantation but has not been consistently linked to early, nonfatal, hospitalized heart disease (HHD). With the United States Renal Data System database, 29,597 patients who received a kidney transplant between January 1, 1996, and July 31, 2000, with Medicare as the primary payer, and were monitored until December 31, 2000, were studied. Cox proportional-hazards regression models were used to calculate the association of recipient estimated GFR (eGFR) at 1 yr after renal transplantation, as determined with the Modification of Diet in Renal Disease formula, with hospitalization for treatment of acute coronary syndromes (ACS) (International Classification of Diseases, version 9, code 410.x or 411.x) or congestive heart failure (CHF) (code 428.x) 1 to 3 yr after renal transplantation. Rates of ACS and CHF were 2.2 and 4.9%, respectively, for patients with eGFR of <44.8 ml/min per 1.73 m(2), compared with 1.2 and 1.4% for patients with eGFR of >69.7 ml/min per 1.73 m(2). Reduced eGFR (<44.8 ml/min per 1.73 m(2), compared with >69.7 ml/min per 1.73 m(2)) at the end of the first 1 yr after transplantation was independently associated with increased risks of both ACS (adjusted hazard ratio, 2.16; 95% confidence interval, 1.39 to 3.35) and CHF (adjusted hazard ratio, 2.95; 95% confidence interval, 2.24 to 3.90). It was concluded that early renal insufficiency (approximately stage 3 chronic kidney disease) was associated with higher rates of HHD 1 to 3 yr after kidney transplantation. Preservation of renal function after renal transplantation may reduce the rates of HHD, and renal transplant recipients with reduced eGFR should be considered at high risk of developing cardiovascular disease.

Timing in the normal pharyngeal swallow. Prospective selection and evaluation of 16 normal asymptomatic patients.

A review of timing of pharyngeal events with radiography has been made. A prospective selection of normal asymptomatic patients presenting for a gastrointestinal evaluation was made and timing of 55 events in the videorecorded pharyngeal swallow in these patients was performed. Only 16 normal asymptomatic patients as defined for selection were found among 870 patients presenting for gastroesophageal examination. A detailed description of their timing observations is presented. The timing data were used to temporally order events in the pharyngeal swallow. This ordering of events in the pharyngeal swallow and the data upon which it is based are reported here in detail.

Intravenous immune globulin therapy for early-onset sepsis in premature neonates*

Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.

Graft Loss and Acute Coronary Syndromes after Renal Transplantation in the United States

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.