University of Miami Hospital

BACKGROUND: Infertility affects an estimated 15% of couples globally, amounting to 48.5 million couples. Males are found to be solely responsible for 20-30% of infertility cases and contribute to 50% of cases overall. However, this number does not accurately represent all regions of the world. Indeed, on a global level, there is a lack of accurate statistics on rates of male infertility. Our report examines major regions of the world and reports rates of male infertility based on data on female infertility. METHODS: Our search consisted of systematic reviews, meta-analyses, and population-based studies by searching the terms "epidemiology, male infertility, and prevalence." We identified 16 articles for detailed study. We typically used the assumption that 50% of all cases of infertility are due to female factors alone, 20-30% are due to male factors alone, and the remaining 20-30% are due to a combination of male and female factors. Therefore, in regions of the world where male factor or rates of male infertility were not reported, we used this assumption to calculate general rates of male factor infertility. RESULTS: Our calculated data showed that the distribution of infertility due to male factor ranged from 20% to 70% and that the percentage of infertile men ranged from 2·5% to 12%. Infertility rates were highest in Africa and Central/Eastern Europe. Additionally, according to a variety of sources, rates of male infertility in North America, Australia, and Central and Eastern Europe varied from 4 5-6%, 9%, and 8-12%, respectively. CONCLUSION: This study demonstrates a novel and unique way to calculate the distribution of male infertility around the world. According to our results, at least 30 million men worldwide are infertile with the highest rates in Africa and Eastern Europe. Results indicate further research is needed regarding etiology and treatment, reduce stigma & cultural barriers, and establish a more precise calculation.

BACKGROUND: HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. METHODS: To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected. CONCLUSIONS: HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Brand equity is very important to marketers of consumer goods and services. Brand equity facilitates in the effectiveness of brand extensions and brand introductions. This is because consumers who trust and display loyalty toward a brand are willing to try to adopt brand extensions. While there have been methods to measure the financial value of brand equity, measurement of customer‐based brand equity has been lacking. Presents a scale to measure customer‐based brand equity. The customer‐based brand equity scale is developed based on the five underlying dimensions of brand equity: performance, value, social image, trustworthiness and commitment. In empirical tests, brands that scored higher on the customer‐based brand equity scale generally had higher prices. Discusses the implications for managers.

Magnetic resonance images of the shoulders of ninety-six asymptomatic individuals were evaluated to determine the prevalence of findings consistent with a tear of the rotator cuff. The scans were reviewed independently by two diagnostic radiologists who are experienced in the interpretation of magnetic resonance images of the shoulder. The over-all prevalence of tears of the rotator cuff in all age-groups was 34 per cent (thirty-three). There were fourteen full-thickness tears (15 per cent) and nineteen partial-thickness tears (20 per cent). The frequency of full-thickness and partial-thickness tears increased significantly with age (p < 0.001 and 0.05, respectively). Twenty-five (54 per cent) of the forty-six individuals who were more than sixty years old had a tear of the rotator cuff: thirteen (28 per cent) had a full-thickness tear and twelve (26 per cent) had a partial-thickness tear. Of the twenty-five individuals who were forty to sixty years old, one (4 per cent) had a full-thickness tear and six (24 per cent) had a partial-thickness tear. Of the twenty-five individuals who were nineteen to thirty-nine years old, none had a full-thickness tear and one (4 per cent) had a partial-thickness tear. Magnetic resonance imaging identified a high prevalence of tears of the rotator cuff in asymptomatic individuals. These tears were increasingly frequent with advancing age and were compatible with normal, painless, functional activity. The results of the present study emphasize the potential hazards of the use of magnetic resonance imaging scans alone as a basis for the determination of operative intervention in the absence of associated clinical findings.

Department of Anesthesiology, University of Colorado Medical Center and the Veterans Administration Hospital, Denver, Colorado. Dr. Aldrete's present address: University of Miami Medical School, Miami, Florida 33136. Read at the 44th Congress of the International Anesthesia Research Society, March 15–19, 1970, Palm Springs, California.

UNLABELLED: One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores > or =2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (> or =2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a > or =1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. CONCLUSION: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

We measured the in situ biomechanical properties of knee joint cartilage from five species (bovine, canine, human, monkey, and rabbit) to examine the biomechanical relevance of animal models of human knee joint injuries and osteoarthritis. In situ biphasic creep indentation experiments were performed to simultaneously determine all three intrinsic material coefficients (aggregate modulus, Poisson's ratio, and permeability) of the cartilage as represented by the linear KLM biphasic model. In addition, we also assessed the effects of load bearing on these intrinsic properties at "high" and "low" weight-bearing regions on the distal femur. Our results indicate that significant differences exist in some of these material properties among species and sites. The aggregate modulus of the anterior patellar groove within each species is the lowest among all sites tested, and the permeability of the patellar groove cartilage is the highest and does not vary among species. Similarly, the Poison's ratio in the patellar groove is the lowest in all species, except in the rabbit. These results lead to the conclusion that patellar groove cartilage can undergo greater and faster compression. Thus, under high compressive loads, the cartilage of the patellar groove surface can more rapidly compress to create a congruent patellofemoral joint articulation. For any given location, no differences were found in the aggregate modulus among all the species, and no correlation was found between aggregate modulus and thickness at the test site. Thus, in the process of selecting a suitable experimental animal model of human articular cartilage, it is essential to consider the significant interspecies differences of the mechanical properties.

BACKGROUND: Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome. METHODS AND RESULTS: The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%; P=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR. Sphericity change from diastole to systole was also significantly reduced in MR patients. Patients with MR were more likely to experience cardiovascular mortality (29% versus 12%; P<.001), severe heart failure (24% versus 16%; P=.0153), and the combined end point of cardiovascular mortality, severe heart failure, or recurrent myocardial infarction (47% versus 29%; P<.001). The presence of MR was an independent predictor of cardiovascular mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04). CONCLUSIONS: Mild MR is an independent predictor of post-MI mortality. As such, it adds important information for risk stratification of post-MI patients.

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Until now oligonephropathy to indicate "too few nephrons" has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight < or = 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < or = 40 days vs. long survival > or = 40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with "basophilic S-shaped bodies" was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving > or =40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman's capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

Carbonate sediments are prone to rapid and pervasive diagenetic alterations that change the mineralogy and pore structure within carbonate rocks. In particular, cementation and dissolution processes continuously modify the pore structure to create or destroy porosity. In extreme cases these modifications can completely change the mineralogy from aragonite/calcite to dolomite, or reverse the pore distribution whereby original grains are dissolved to produce pores as the original pore space is filled with cement to form the rock (Figure 1). All these modifications alter the elastic properties of the rock and, therefore, the sonic velocity. The result is a dynamic relationship among diagenesis, porosity, pore-type, and sonic velocity. The result is a wide range of sonic velocity in carbonates, in which compressional-wave velocity (VP) ranges from 1700 to 6600 m/s and shear-wave velocity (VS) from 600 to 3500 m/s.

BACKGROUND: Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. METHODS AND RESULTS: The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients <18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. CONCLUSIONS: In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults.

CD44 is a facultative proteoglycan implicated in cell adhesion and trafficking, as well as in tumor survival and progression. We demonstrate here that CD44 heparan sulfate proteoglycan (CD44HSPG) recruits proteolytically active matrix metalloproteinase 7 (matrilysin, MMP-7) and heparin-binding epidermal growth factor precursor (pro-HB-EGF) to form a complex on the surface of tumor cell lines, postpartum uterine and lactating mammary gland epithelium, and uterine smooth muscle. The HB-EGF precursor within this complex is processed by MMP-7, and the resulting mature HB-EGF engages and activates its receptor, ErbB4, leading to, among other events, cell survival. In CD44(-/-) mice, postpartum uterine involution is accelerated and maintenance of lactation is impaired. In both uterine and mammary epithelia of these mice, MMP-7 localization is altered and pro-HB-EGF processing as well as ErbB4 activation are decreased. Our observations provide a mechanism for the assembly and function of a cell surface complex composed of CD44HSPG, MMP 7, HB-EGF, and ErbB4 that may play an important role in the regulation of physiological tissue remodeling.

BACKGROUND: Radial access for percutaneous coronary intervention (r-PCI) is associated with reduced vascular complications; however, previous reports have shown that <2% of percutaneous coronary intervention (PCI) procedures in the United States are performed via the radial approach. Our aims were to evaluate temporal trends in r-PCI and compare procedural outcomes between r-PCI and transfemoral PCI. METHODS AND RESULTS: We conducted a retrospective cohort study from the CathPCI registry (n=2 820 874 procedures from 1381 sites) between January 2007 and September 2012. Multivariable logistic regression models were used to evaluate the adjusted association between r-PCI and bleeding, vascular complications, and procedural success, using transfemoral PCI as the reference. Outcomes in high-risk subgroups such as age ≥75 years, women, and patients with acute coronary syndrome were also examined. The proportion of r-PCI procedures increased from 1.2% in quarter 1 2007 to 16.1% in quarter 3 2012 and accounted for 6.3% of total procedures from 2007 to 2012 (n=178 643). After multivariable adjustment, r-PCI use in the studied cohort of patients was associated with lower risk of bleeding (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.54) and lower risk of vascular complications (adjusted odds ratio, 0.39; 95% confidence interval, 0.31-0.50) in comparison with transfemoral PCI. The reduction in bleeding and vascular complications was consistent across important subgroups of age, sex, and clinical presentation. CONCLUSIONS: There has been increasing adoption of r-PCI in the United States. Transradial PCI now accounts for 1 of 6 PCIs performed in contemporary clinical practice. In comparison with traditional femoral access, transradial PCI is associated with lower vascular and bleeding complication rates.

The phenomenon of postpacing depression of cardiac pacemakers was utilized to evaluate the sinus-node function in 56 patients by analyzing the sinus-node recovery time (SRT), that is, the interval between the last paced P wave and the following sinus P wave. Corrected SRT (CSRT) is defined as the recovery interval in excess of the sinus cycle (SRT — sinus cycle length). The SRT was measured following sinus-node suppression by (1) isolated premature beats (PABs) and (2) atrial pacing (AP) at rates of 100 to 140/min for periods of 2 to 5 min at each level. Twenty-eight patients had normal heart rates (group A), and 28 patients had sinus bradycardia (SB; group B). Ten of the 28 patients with SB were restudied after receiving atropine (2 mg intravenously). The CSRT with PABs was similar in both group A and group B patients and remained essentially unchanged after atropine despite a decrease in sinus cycle length. The phenomenon of interpolated PABs was demonstrated in seven of the 56 patients. In 27 of the 28 patients with normal heart rates (group A), the CSRT with AP ranged from 110 to 525 msec and was essentially independent of the rate and duration of AP. In the remaining one patient of group A, despite a normal heart rate, the CSRT was prolonged (1810 msec) and directly dependent on the rate and duration of AP. In 12 of the 28 patients with SB, the CSRT was comparable to that in group A (≦525 msec). In the remaining 16 patients with SB (group B), the CSRT ranged from 560 to 3740 msec and was usually directly proportional to the rate and duration of AP. After atropine in most of the patients with a prolonged CSRT, the CSRT remained abnormal whereas in others junctional escape beats appeared first, followed eventually by normal sinus rhythm. In a single patient with SB and an abnormal CSRT, restudy 7½ months later again showed a prolonged CSRT indicating the reproducibility of the measurement. The CSRT with AP provides a potentially useful clinical means of assessing the sinus-node function and thereby aids in the diagnosis of the "sick sinus syndrome." It is stressed that AP was found to be more reliable than PABs in eliciting an abnormal response. Furthermore, a normal sinus (atrial) rate does not necessarily provide assurance of a normal sinus-node response to AP, that is, normal sinus-node function.

The development of effective antineoplastic therapies for childhood cancer is a great success in modern medicine. Five year survival rates of children diagnosed with cancer in the USA and Western Europe in excess of 70% make long term survivors of childhood cancer a steadily increasing population. Although there is much to celebrate, new challenges lie ahead in treating the systemic sequelae of chemotherapy.1 Results from the Childhood Cancer Survivor Study (CCSS) showed that 30 years after treatment, the cumulative incidence of chronic health conditions in long term survivors reaches 73%, with a cumulative incidence of 42% for severe, disabling, or life threatening conditions or death.2 Severe conditions, that are significantly more common in childhood cancer survivors than in their siblings, include: major joint replacement (relative risk (RR) 54.0), congestive heart failure (RR 15.1), second malignant neoplasm (RR 14.8), severe cognitive dysfunction (RR 10.5), coronary artery disease (RR 10.4), cerebrovascular accident (RR 9.3), and renal failure (RR 8.9).2 Previous CCSS results found that patients who had survived at least 5 years after diagnosis had 10.8-fold increased rates of all cause mortality.3 The standardised mortality ratio for cardiac causes was 8.2 times higher than expected and the cumulative probability of cardiac death increased 15–25 years after cancer diagnosis. A similar study in a large Nordic cohort documented a standardised mortality ratio of 5.8 for cardiac death and elevated rates of sudden, presumed arrhythmic, deaths.4 Chief among adverse late effects is the cardiovascular toxicity of anthracyclines.5–11 Unfortunately, despite well documented dose related toxicity, the superior disease-free survival rates of regimens including anthracyclines leave limited viable treatment alternatives and the majority of long term paediatric cancer survivors in the Pediatric Oncology Group received an anthracycline during treatment.12 ### Mechanism of cardiotoxicity Several cytotoxic biochemical changes follow anthracycline exposure in …

Thrombotic thrombocytopenic purpura, the acute form of which is usually fatal, is characterized clinically by thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic signs and renal dysfunction, and pathologically by diffuse thrombotic occlusions in the microcirculation, in which platelets are consumed.1 2 3 4Since the pathogenesis of this disease is not understood, treatment has been empirical or with an assumed rationale. Among the various modes of therapy tried, four are especially advocated: splenectomy and use of antiplatelet agents, of high doses of glucocorticoids, and of exchange transfusions. The value of splenectomy remains undefined.5 Proponents of antiplatelet treatment argue that whether or not platelet adhesion . . .

PURPOSE: We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS: A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS: Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS: NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.

BACKGROUND: Aspiration pneumonia is common among frail elderly persons with dysphagia. Although interventions to prevent aspiration are routinely used in these patients, little is known about the effectiveness of those interventions. OBJECTIVE: To compare the effectiveness of chin-down posture and 2 consistencies (nectar or honey) of thickened liquids on the 3-month cumulative incidence of pneumonia in patients with dementia or Parkinson disease. DESIGN: Randomized, controlled, parallel-design trial in which patients were enrolled for 3-month periods from 9 June 1998 to 19 September 2005. SETTING: 47 hospitals and 79 subacute care facilities. PATIENTS: 515 patients age 50 years or older with dementia or Parkinson disease who aspirated thin liquids (demonstrated videofluoroscopically). Of these, 504 were followed until death or for 3 months. INTERVENTION: Participants were randomly assigned to drink all liquids in a chin-down posture (n = 259) or to drink nectar-thick (n = 133) or honey-thick (n = 123) liquids in a head-neutral position. MEASUREMENTS: The primary outcome was pneumonia diagnosed by chest radiography or by the presence of 3 respiratory indicators. RESULTS: 52 participants had pneumonia, yielding an overall estimated 3-month cumulative incidence of 11%. The 3-month cumulative incidence of pneumonia was 0.098 and 0.116 in the chin-down posture and thickened-liquid groups, respectively (hazard ratio, 0.84 [95% CI, 0.49 to 1.45]; P = 0.53). The 3-month cumulative incidence of pneumonia was 0.084 in the nectar-thick liquid group compared with 0.150 in the honey-thick liquid group (hazard ratio, 0.50 [CI, 0.23 to 1.09]; P = 0.083). More patients assigned to thickened liquids than those assigned to the chin-down posture intervention had dehydration (6% vs. 2%), urinary tract infection (6% vs. 3%), and fever (4% vs. 2%). LIMITATIONS: A no-treatment control group was not included. Follow-up was limited to 3 months. Care providers were not blinded, and differences in cumulative pneumonia incidence between interventions had wide CIs. CONCLUSION: No definitive conclusions about the superiority of any of the tested interventions can be made. The 3-month cumulative incidence of pneumonia was much lower than expected in this frail elderly population. Future investigation of chin-down posture combined with nectar-thick liquid may be warranted to determine whether this combination better prevents pneumonia than either intervention independently.