Non-parametric comparison of relative versus cause-specific survival in Surveillance, Epidemiology and End Results (SEER) programme breast cancer patients.

Cancer-related mortality can be measured by two dissimilar methods: cause-specific survival (based on mortality attributed to a specific cause), and relative survival (based on mortality relative to a matched cohort). We used both methods to determine actuarial survival in a population of 119,502 breast cancer patients from the Surveillance, Epidemiology and End Results (SEER) programme data set, with 20 years of follow-up. The population was divided into four strata by patient age and tumour stage. In all strata, there was only minimal deviation between the two survival methods. Of particular interest was the cause-specific treatment of patients recorded as dead of unknown cause, i.e. those deaths that could not be attributed with certainty to either 'breast cancer' or to 'other causes'. Findings suggest that the most reliable results may be obtained by apportioning these deaths between 'dead of cause' and 'withdrawn at the time of death'. This apportionment is based on the relative number of deaths attributed to 'breast cancer' versus 'other causes'.

1,2,5-Thiadiazole derivatives are potent and selective ligands at human 5-HT1A receptors.

Amino acid derivatives of 1,2,5-thiadiazol-3-yl-piperazine related to (+)-WAY-100135 and WAY-100635 are potent 5-HT1A receptor agonists and antagonists, which have selective affinity for 5-HT1A receptors versus alpha1 and dopamine (D2, D3, and D4) receptors.

Tardive dyskinesia--diagnostic issues, subsyndromes, and concurrent movement disorders: a study of state hospital inpatients referred to a movement disorder consultation service.

Of 49 state hospital patients referred for movement disorder consultation for tardive dyskinesia (TD), 11 (23.9%) of 46 meeting inclusion criteria had movement disorders other than TD. These other disorders led to a false diagnosis of TD in 6 subjects (12.2%). Between-day dyskinesia variability affected TD ascertainment in only 3.2 percent of subjects. Prevalences of other neurological conditions in the 30 patients identified with definite TD were parkinsonism (90%), dystonia (25%), akathisia (16%), cerebellar signs (40%), dysmetria (23%), cerebellar tremor (17%), tardive dystonia (3.3%), and tardive akathisia (3.3%). Concurrence rates of parkinsonism with TD varied significantly according to which clinical signs were used to define parkinsonism. Using a rating score threshold of at least mild, rigidity occurred in 79.3 percent, bradykinesia in 55.2 percent, and resting tremor in 41.4 percent of subjects with TD; more significant rigidity occurred in 41.4 percent, bradykinesia in 31.0 percent, and resting tremor in 20.7 percent. Concurrence rates of neurological conditions with TD subsyndromes were distributed rather evenly according to condition prevalences, except for an association of cervicotruncal TD with bradykinesia (perhaps because of ventromedial striatal presynaptic and postsynaptic D2 blockade, respectively). These findings, as well as the occurrence of equal gender ratio and relative under-representation of bipolar and alcohol disorders in subjects with definite TD, are discussed.

The relationship between volume status, hydration, and radiographic findings in the diagnosis of community-acquired pneumonia.

BACKGROUND: Many clinicians believe the radiographic expression of community-acquired pneumonia (CAP) is affected by the fluid volume status of the patient. However, there are very few data to support or refute this concept. With this study we began to examine the relationship between admission fluid volume status and the radiographic expression of CAP. METHODS: Using a retrospective chart review, we examined 376 consecutive inpatient encounters with the diagnosis of pneumonia at discharge from a community teaching hospital. Patients were evaluated by age, sex, admission serum sodium, blood urea nitrogen (BUN) level, creatinine, and fluid administered in the first 48 hours of treatment. We classified these patients as either showing radiographic progression (P) or no radiographic progression (NP) by comparison of admission and follow-up radiographs. RESULTS: A total of 125 patient encounters satisfied inclusion criteria for the study. Using the Student t test we noted a statistically significant difference between the P and NP groups for BUN level (P=.02), volume of fluid administered during the first 48 hours (P=.04), and marginally for age (P=.05). The P group had higher BUN levels (mean=34 vs 24), more 48-hour fluid intake (mean=5824 mL vs 4764 mL), and younger age (mean=59 years vs 66 years) than the NP group. Logistic regression poorly predicted which patients would have worsening infiltrate on the second radiograph. CONCLUSIONS: Elevated admission BUN level and higher fluid volume administered in the first 48 hours of admission were associated with worsening radiographic findings of pneumonia after hydration. Prospective studies are needed for confirmation of our results.

Postoperative lumbar microdiscectomy pain. Minimalization by irrigation and cooling.

STUDY DESIGN: Seventy patients undergoing de novo lumbar microdiscectomy were prospectively randomized into a control group and a group in which cold intraoperative wound irrigation along with postoperative wound cooling was used. Postoperative analgesia requirements and length of hospital stay were analyzed and correlated. OBJECTIVES: To evaluate the role of intraoperative cold irrigation and postsurgical cooling in minimizing postoperative lumbar discectomy pain. SUMMARY OF BACKGROUND DATA: Regulated hypothermia has been used frequently in pain reduction; however, the efficacy of such a strategy in lumbar disc procedures has not been established. METHODS: Seventy patients (43 men and 27 women), operated on the first time for lumbar disk herniation were prospectively randomized into two groups. A standard microdiscectomy was performed on all patients. In cohort A the wound site was irrigated with a cold (18 C) 5% bacitracin solution for 5 minutes. Additionally, a cooling microtemperature pump was placed on the wound site for 24 hours after surgery. The patients in the control group (cohort B) were treated in a standard fashion without additional hypothermic therapy. All patients received postoperative analgesia through a self-administered morphine pump. The amount of postoperative analgesia received was calculated in morphine equivalents per kilogram. The length of hospital stay was also noted. RESULTS: The total amount of pain medication was significantly smaller in cohort A than in the control group (cohort B). For the statistical analysis of the results, covariate analyses for both the length of hospital stay and the morphine dose were used, demonstrating a statistically significant difference with P = 0.0001. No postoperative wound infection was noted in either group. CONCLUSIONS: Intraoperative and postoperative wound site cooling is a safe, inexpensive, and efficient therapeutic method. It reduces the patients' postoperative pain, promotes earlier ambulation and decreases the length of hospital stay.

Cervical spinal cord--smaller than considered?

STUDY DESIGN: One hundred two patients with symptoms of cervical radiculopathy, were retrospectively analyzed and their cervical spinal cord diameters obtained. OBJECTIVES: To measure the cervical spinal cord in vivo and to compare the findings with those previously reported in the literature. SUMMARY OF BACKGROUND DATA: Traditionally, autopsy data have served as the linchpin of cervical cord measurements. However, several studies obtained by realtime radiographic methods have failed to confirm such measurements. METHODS: The spinal cord was retrospectively measured in 102 patients. All patients underwent myelogram and postmyelogram computed tomographic scan. Anteroposterior and transverse diameters of the spinal cord were measured from C2 to T1 at the level of each intervertebral disc. The depth of the anterior median fissure and cross-sectional area were measured as well. Plain myelographic films were reviewed but demonstrated no findings contrary to postmyelogram computed tomographic measurements. RESULTS: There was no statistically significant difference in the spinal cord measurements in relation to age or sex. There was an increase in the transverse diameter but not in the anteroposterior diameter in the midcervical spinal enlargement. The anteroposterior diameter decreased linearly. The transverse diameter and the cross-sectional area increased to a maximum at C5, as did the depth of the anterior median fissure. The cervical spinal cord diameter was documented to be 15-20% smaller than has commonly been determined by autopsy data. CONCLUSIONS: Postmyelogram computed tomographic measurements are smaller than those obtained from autopsy data.

Emergency department use by nursing home residents.

STUDY OBJECTIVE: To describe a community's experience with the use of emergency department services by nursing home residents. METHODS: We performed a retrospective chart review of a population-based cohort of nursing home residents in an urban county in central Georgia with 10 nursing homes (1,300 beds) and 4 hospital-based EDs. All ED visits by nursing home residents during 1995 were analyzed. Demographic data, timing of the visit, chief complaint, tests and treatments, disposition, and financial charges were recorded. Further, we calculated the number of ED visits per 100 nursing home patient-years. RESULTS: A total of 873 nursing home residents made 1,488 ED visits. Mean age was 76.0 years; 66.4% were female, and 55.2% were white. Of the transfers, 42.9% occurred during regular working hours. The most common chief complaints were respiratory symptoms (14.4%), altered mental status (10.1%), gastrointestinal symptoms (9.9%), and falls (8.2%); 101 patients (6.8%) were transferred for malfunction of a gastrostomy tube. The most common laboratory tests were complete blood cell count (69.5%), chest radiograph (52.0%), electrocardiogram (45.0%), urinalysis (42.7%), and determination of electrolytes (42.7%). A total of 42.4% of the ED visits led to admission to the hospital. From the 10 nursing homes, there were 110 ED visits per 100 patient-years. A 3.5-fold difference in ED use among these nursing homes could not be explained by age, gender, or other factors. The average .charge per ED visit was $1,239. CONCLUSION: Elders living in nursing homes are frequently transferred to EDs for costly medical evaluations, and more than 40% of such visits lead to admission to the hospital.

Multivariate analysis of factors associated with postoperative pulmonary complications following general elective surgery.

OBJECTIVE: To develop a predictive model identifying perioperative conditions associated with postoperative pulmonary complications (PPCs). DESIGN: A prospective survey of patients whose preoperative history and physical examination, spirometric, PaO2 and PaCO2 analysis, and operative results were recorded. These patients underwent postoperative cardiopulmonary examinations until they were discharged from the hospital; their medical records were also reviewed until they were discharged from the hospital. SETTING: The Louisville Veterans Administration Medical Center, Louisville, Ky. PATIENTS: A randomly chosen sample of patients aged 40 years or older who required elective, nonthoracic surgery under general or spinal anesthesia and who were hospitalized at least 24 hours postoperatively. MAIN OUTCOME MEASURE: An analysis of risk factors associated with the development of 1 or more of the following conditions: acute bronchitis, bronchospasm, atelectasis, pneumonia, adult respiratory distress syndrome, pleural effusion, pneumothorax, prolonged mechanical ventilation, or death secondary to acute respiratory failure. RESULTS: Postoperative pulmonary complications developed in 16 (11%) of 148 patients. The risk factors found to be higher among those with PPCs compared with those without PPCs were postoperative nasogastric intubation (81% vs 16%, P<.001), preoperative sputum production (56% vs 21%, P=.005), and longer anesthesia duration (480 vs 309 minutes, P<.001). Upper abdominal surgery was performed in 11 (69%) of the 16 patients with PPCs and in 20 (15%) of the 132 patients without PPCs (P<.001); this difference lost significance in multivariate analysis. The final linear logistic model included postoperative nasogastric intubation (odds ratio [OR], 21.8), preoperative sputum production (OR, 4.6), and longer anesthesia duration (OR exp[0.01x] for an increase in x minutes) (1 minute of additional anesthesia time increases the OR to 1.01), resulting in 92% accuracy in predicting PPCs. CONCLUSIONS: We identified 3 potentially modifiable risk factors for PPCs. If validated, our results may lead to modifications of perioperative care that will further reduce PPCs.

Is primary care physician supply correlated with health outcomes?

Assessment of the relation between life indicators and health outcomes is a complex problem. The authors' analysis uses descriptive canonical correlation, and their solution suggests that socioeconomic factors play a major role in health outcomes. The supply of primary care physicians has a lesser but still important role: canonical correlation suggests no apparent role in enhancing health outcomes among the elderly but a larger role in improving health among the young. The authors' analysis does support the notion that specialist physician supply has no correlation with a wide range of health outcomes.

Esophagogastroduodenoscopy performed by a family physician. A case series of 793 procedures.

BACKGROUND: Primary care physicians are performing an increasing number of gastrointestinal endoscopies. The purpose of this research is to present a large case series of diagnostic esophagogastroduodenoscopies (EGDs) performed by a family physician in a solo rural practice. METHODS: We present a retrospective chart review, including demographic characteristics, indications, endoscopic and pathologic findings, and complications for every EGD performed by a family physician over a 7-year period. RESULTS: Seven hundred ninety-three EGDs were performed on 602 patients (421 women, 181 men), with a mean age of 51.8 years. In 99% of procedures, the second portion of the duodenum was intubated. The most common indications for EGD were abdominal pain (60.5%), gastrointestinal bleeding (23.0%), dysphagia (11.6%), and heart-burn (10.7%). A total of 451 biopsies were obtained in 385 procedures, mostly from the distal esophagus (38%) or gastric antrum (37%). Common endoscopic diagnoses were gastritis (54%), esophagitis (25%), and normal study (15%). There were only two malignancies detected, one gastric lymphoma and one carcinoma metastatic to the stomach. One minor complication (0.13%) occurred, an immediate urticarial rash after intravenous meperidine. CONCLUSIONS: Experienced family physicians can safely and competently perform diagnostic EGD and provide this important service to their community.

High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells.

Osteoblasts and adipocytes originate from common mesenchymal precursors. With aging, there is a decrease in osteoprogenitor cells that parallels an increase of adipocytes in bone marrow. We observed that rabbit serum (RS) induces adipocyte-like differentiation in human osteosarcoma SaOS-2/B10 and MG-63 cell lines, in rat ROS17/2.8 cells, and in mouse calvaria-derived osteoblastic MB1.8 cells, as evidenced by the accumulation of Oil Red O positive lipid vesicles and the decrease in alkaline phosphatase expression. Both SaOS-2/B10 and MG-63 cells, but not ROS17/2.8 nor MB1.8 cells, express significant levels of PPARgamma mRNA, a member of the peroxisome proliferator activated receptor (PPAR) family that has been implicated in the control of adipocyte differentiation. However, both ROS17/2.8 and MG-63 cells express significant levels of the adipocyte selective marker, aP2 fatty acid binding mRNA, which can be further increased by RS. These cell types express PPARdelta/NUC-1 but not PPARalpha, indicating that cells that do not express either PPARgamma or PPARalpha are capable of differentiating into adipocyte-like cells. Transfection experiments in COS cells showed that compared with fetal bovine serum (FBS), RS is rich in agents that stimulate PPAR-dependent transcription. The stimulatory activity was ethyl acetate extractable and was 35-fold more abundant in RS than in FBS. Purification and analysis revealed that the major components of this extract are free fatty acids. Furthermore, the same fatty acids, a mixture of palmitic, oleic, and linoleic acids, activate the PPARs and induce adipocyte-like differentiation of both ROS17/2.8 and SaOS-2/B10 cells. These findings suggest that fatty acids or their metabolites can initiate the switch from osteoblasts to adipocyte-like cells.

The effects of isoproterenol on the cardiac conduction system: site-specific dose dependence.

INTRODUCTION: Isoproterenol is used to assess and facilitate AV nodal conduction, and thus potentiate the induction of supraventricular arrhythmias. It is commonly administered in increasing doses until a predetermined decrease in sinus cycle length, usually 20% to 30%, occurs. This regimen may result in undesirable side effects. We have observed that effects of isoproterenol on the AV node may occur prior to achieving the target sinus cycle length. The purpose of this study was to determine whether the sinus and AV nodes have equal sensitivity to isoproterenol. METHODS AND RESULTS: Thirty-eight consecutive patients, who underwent electrophysiologic evaluation for a variety of indications, were given incremental doses of isoproterenol at 0.007, 0.014, 0.021, and 0.028 microgram/kg per minute. Sinus cycle length and AV node function were assessed at baseline and after 5 minutes at each dose. The percent change from baseline in AV node function was compared with the change in sinus cycle length at each dose interval. Significantly greater decreases were observed in the anterograde and retrograde AV nodal Wenckebach cycle length (P < 0.0001) than in the sinus cycle length at the lowest isoproterenol dose (0.007 microgram/kg per min). These differences were not apparent at higher doses. A sustained supraventricular tachycardia was inducible in 15 of 38 patients in the presence of isoproterenol, of which 40% occurred at the lowest dose. CONCLUSIONS: The AV node is more sensitive than the sinus node to the effects of isoproterenol. Lower doses of isoproterenol than those commonly used may often facilitate the induction of a supraventricular tachyarrhythmia, thus reducing side effects.

Comparison of parametric and non-parametric survival methods using simulated clinical data.

We derived three parametric survival models (the log-normal, log logit, and Weibull) from the clinical data of chemotherapy trials for stage II breast cancer. We then used these models to generate simulated survival data, which we analysed using both parametric (log-normal) and non-parametric (logrank, Gray-Tsiatis and Laska-Meisner) methods. With limited follow-up (5 years), the non-parametric tests had greater power than the log-normal model. This advantage diminished, however, with extended follow-up (15 years). Furthermore, only the log-normal model could distinguish reliably a survival advantage due to an increase in cured fraction from an advantage due to an increase in time to failure.

Colonoscopy performed by a family physician. A case series of 751 procedures.

BACKGROUND: Colonoscopy, including biopsy and polypectomy, is a procedure not commonly performed by primary care physicians. The purpose of this research was to present a large case series of colonoscopic procedures performed by a family physician in a rural practice. METHODS: A chart review of every colonoscopy procedure performed by a family physician over a 7-year period determined the demographic characteristics, indications, findings, and complications for each procedure. RESULTS: A total of 751 colonoscopies were performed on 555 patients (347 women and 208 men), with a mean age of 53.8 years. In 91.5% of procedures, the cecum was intubated. The most common indications for colonoscopy were bleeding (49.9%), polyp follow-up (20.9%) abdominal pain (11.7%), diarrhea (11.6%), and abnormal findings on flexible sigmoidoscopy (8.4%). Three hundred sixteen benign polyps were discovered and removed by either biopsy or polypectomy. There were 184 adenomatous colorectal polyps found in 134 (17.8%) colonoscopies. Of these 184 adenomatous polyps, 106 (58%) were potentially within reach of the flexible sigmoidoscope. Only three adenocarcinomas were discovered during the entire study period. There was only one major procedural complication: a patient experienced blood oozing from a polypectomy stump; cautery stopped the bleeding, and the patient was hospitalized overnight, with no further intervention or transfusion required. There were five other self-limited complications, including adverse reactions to sedation and infiltration at the intravenous site. CONCLUSIONS: Colonoscopy with polypectomy that was safely and competently performed in a solo rural practice adds to the evidence that experienced family physicians can provide this important service to their community.

Primary ablation of atrial flutter and atrial fibrillation.

Direct treatment of atrial flutter and atrial fibrillation--that is, attempting to prevent arrhythmia recurrences by ablating atrial tissue--has been a challenge because of uncertainty about the location of optimal target tissues as well as the amount of atrial tissue requiring destruction to effect cure. Advances have yielded success rates for ablation of the common form of atrial flutter comparable to those for other types of supraventricular tachycardia and provide reason for optimism about the use of catheter techniques, to treat atrial fibrillation definitively. This article discusses some of these advances as well as the current status of catheter ablation for atrial flutter and atrial fibrillation and, finally, what the future may bring.

Identification of fatty acid methyl ester as naturally occurring transcriptional regulators of the members of the peroxisome proliferator-activated receptor family.

The nuclear hormone receptors NUC-1 (PPAR delta) and PPAR alpha are members of the peroxisome proliferator-activated receptor (PPAR) family. The members of this receptor family are activated by agents that stimulate peroxisome proliferation, free fatty acids, prostaglandin 12 metabolites, and agents considered for the therapy of insulin-independent diabetes mellitus. To identify putative physiological agents that activate NUC-1, we tested the ability of acetone extracts of various rat tissues to activate the transcription of an MMTV-luciferase reporter gene, via a GR/NUC-1 hybrid receptor. GR/NUC-1 contains the ligand binding region of the NUC-1 receptor and the DNA binding domain of the glucocorticoid receptor. Using this assay, we found stimulatory activity in the pancreas, which upon purification and characterization was identified as methyl-palmitate, known to be enriched in pancreatic lipids. In addition, we determined that ethyl esters of palmitic and oleic acids are also potent activators of this receptor. Thus, fatty acid ester formation may control the cellular concentrations of fatty acids, and acyl-ester formation may play a role in the control of metabolic pathways and the activation of the PPAR.

What providers need to know bout the False Claims Act.

In the 1990s, the Federal government's antifraud efforts increasingly have focused on the healthcare industry, and the False Claims Act, a powerful law designed to curb fraud against the Federal Treasury, has been one of the government's most potent weapons. One reason for the act's potency is its qui tam provision, which encourages whistleblowers to expose fraud in return for a substantial percentage of money the government recovers. The False Claims Act has been used against healthcare providers in the following areas: billing for services or supplies not actually provided, billing for nonreimbursable services, using false diagnoses to justify claims, and cheating in government performance evaluations.