Hospitalisation and resource utilisation in patients with schizophrenia following initiation of risperidone long-acting therapy in the Veterans Affairs Healthcare System.

OBJECTIVE: To examine hospitalisation rates and resource utilisation following initiation of risperidone long-acting therapy (RLAT) among US veterans with schizophrenia. METHODS: Encounter data were analysed from the Ohio Veterans Affairs (VA) Healthcare System. Adult patients (schizophrenia or schizoaffective disorder) with ≥1 medical or hospital visits with a diagnosis code of 295.xx, continuous enrolment from January 2003 through January 2006, and ≥4 injections of RLAT were selected. Analyses compared psychiatric-related resource utilisation pre- and post-exposure to RLAT; each patient served as his/her own control. The pre-exposure and post-exposure periods defined were equal in duration (e.g., a 6-month post-exposure period was matched with a 6-month pre-exposure period). Descriptive and comparative analyses (paired t tests, McNemar's test) were performed. RESULTS: Patients (n=106) were 51.9 years old (+/-10.2), male (93%), white (73%) and received on average 14 RLAT doses (+/-9.7; range, 4-47 injections) over 309 days (+/-196; range, 42-737 days). Most experienced a psychiatric-related hospitalisation prior to initiation; less than half experienced hospitalisation after initiation (75% vs. 42%; p<0.001). Relative to pre-initiation, fewer psychiatric-related hospitalisations (mean [SD] change, -0.8 [2.0]; p<0.001), shorter length of stay (-25 [63.6] days; p<0.001), fewer inpatient days/month (-3.1 [7.2] days) and one (2.8) additional outpatient visit/month (p<0.001) occurred post-initiation. LIMITATIONS: The absence of a control group in this pre-/post comparison may have resulted in exposure to a regression to the mean effect. Also, this study evaluated only one cohort of patients in a VA healthcare setting. CONCLUSIONS: VA patients with schizophrenia and schizoaffective disorder treated with RLAT experienced fewer hospitalisations and psychiatric-related inpatient days following RLAT initiation. Further studies utilising a control group and in non-VA populations are warranted.

Risk factors for mortality-morbidity after emergency-urgent colorectal surgery.

BACKGROUND: The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. MATERIALS AND METHODS: All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. RESULTS: The median age of patients was 73 (range 17-98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm(3) (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63-6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score > or =3 (OR = 2.9, 95% CI 1.9-4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4-7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4-3.4, p = 0.0003). CONCLUSIONS: The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients' ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.

Long-term analysis of primary nonfunction in liver transplant recipients.

UNLABELLED: Long-term allograft and patient survival following liver transplantation continues to improve with the development of new surgical techniques and immunosuppressive agents. Complications such as primary nonfunction (PNF) have not been well characterized in terms of long-term allograft and patient survival. The aim of this study was to determine the incidence of PNF in liver transplant recipients and patient and graft survival, in addition to identifying temporal trends in these parameters. METHOD: Data were obtained from the United Network for Organ Sharing/Organ Procurement and Transplant Network for all adults (>18 years old) who received a deceased donor liver transplant between January 1990 and December 2004. RESULTS: Of the 58,576 liver transplant recipients, 2061 had PNF, an overall incidence of 3.5%. There was a 30% annual increase in the incidence of PNF between 1990 and 2000; the incidence of PNF peaked at 7%, and then decreased by 20% annually thereafter. No differences in donor and perioperative variables were identified to account for this variation. One-, 3-, and 5-year patient and graft survival for patients with PNF who underwent retransplant were significantly lower than those with primary liver transplant. In conclusion, there has been decreased incidence of PNF among liver transplant recipients in the last decade.

Comparison of stone size and response to analgesic treatment in predicting outcome of patients with renal colic.

The aim of this study was to compare the prognostic value of stone size and response to analgesic treatment in patients with renal colic. We reviewed the charts of patients treated for renal colic in our Emergency Department. The eligibility criteria were a radiological examination demonstrating direct or indirect signs of ureteral obstruction and/or a stone. The primary endpoint was the requirement for surgical treatment. The parameters considered as prognostic factors were pain relief with ketorolac (K) or ketorolac plus opiate treatment (KO), and stone size (>or= or <6 mm). Ninety-five patients were considered for analysis. Of these, 49 (52%) had a stone demonstrated radiologically. Four out of 27 patients (15%) in the KO group and six out of 68 patients (8.8%) in the K group required a surgical procedure to relieve the obstruction (NS). Four out of five patients (80%) with a stone >or=6 mm required a surgical procedure, compared with one out of 44 (2.2%) who had a stone smaller than 6 mm (P<0.001). In conclusion, stone size is a better prognostic factor than the response to analgesic treatment in predicting the clinical outcome of patients with renal colic. A stone >or=6 mm in patients with renal colic should alert the emergency physician that urological complications requiring surgical intervention may occur and that urological management may be warranted.

Hypothyroidism: a frequent event after radiotherapy and after radiotherapy with chemotherapy for patients with head and neck carcinoma.

BACKGROUND: The incidence of hypothyroidism was assessed retrospectively from a data base of 155 patients with head and neck carcinoma who were treated at the Cleveland Clinic Foundation between 1990 and 1997. METHODS: One hundred patients were randomized between radiotherapy (RT) (66-72 grays in single daily fractions) and RT with concurrent chemotherapy (CT) using 5-fluorouracil and cisplatin. An additional 55 patients received RT and CT without randomization. Primary site surgery was performed for tumor persistence or recurrence and included a thyroidectomy in nine patients. These nine patients, along with three patients who had hypothyroidism prior to treatment, were excluded from the analysis. At regular intervals after the completion of treatment, all patients were evaluated for the development of hypothyroidism, defined as a serum thyroid-stimulating hormone (TSH) level > 5.5 microU/mL. RESULTS: With a median follow-up for 143 evaluable patients of 4.4 years (range, 1.5-9.2 years), the 5-year Kaplan-Meier projected incidence rate of hypothyroidism was 48%, and the 8-year projected incidence rate was 67%. The median time to the development of hypothyroidism was 1.4 years (range, 0.3-7.2 years). The likelihood of developing hypothyroidism could not be predicted according to age, gender, primary site, tumor or lymph node status, overall stage, RT dosage to the primary site or to the neck, or inclusion of CT in the treatment plan. Only race proved predictive, with no African-American patients developing hypothyroidism (P = 0.02). CONCLUSIONS: The authors conclude that the incidence rate of hypothyroidism after patients undergo RT for head and neck carcinoma is higher than generally reported and that TSH screening after treatment appears justified.

Colonic J-pouch function in rectal cancer patients: impact of adjuvant chemoradiotherapy.

PURPOSE: The colonic J-pouch technique of reconstruction optimizes functional outcome after proctectomy with coloanal anastomosis. However, the impact of adjuvant chemoradiation therapy on pouch function in rectal cancer patients has not been investigated. METHODS: From January 1994 to December 1999, 74 patients with midrectal or low rectal tumors (less than 10 cm from the anal verge) underwent a proctectomy with coloanal anastomosis with colonic J-pouch reconstruction. Chemoradiation was offered in patients with Stage II and III disease. Radiation therapy was administered using a four-field technique including the anal canal, for a total dose of 50.4 Gy (1.8 Gy/fraction/day). Fifteen patients (20 percent) died with metastatic disease, five (6.8 percent) died of other causes without evidence of recurrence, and five (6.8 percent) were lost to follow-up. In addition, two patients had local recurrence (2.7 percent) at the time of follow-up. Forty-five of 47 eligible patients (96 percent) responded to a questionnaire designed to evaluate specifically the degree of continence and pouch evacuation. RESULTS: The mean age of patients was 68.9 (range, 42-88) years and the mean duration of follow-up was 28.8 (range, 1-69) months. There were 28 patients in the surgery alone group and 17 patients who received either preoperative (13) or postoperative (4) adjuvant chemoradiation therapy. Patients in the surgery alone group had a significantly better degree of continence (mean +/- standard deviation continence score: 18.1 +/- 2.9 vs. 13.3 +/- 4.1, P < 0.001) and were less likely to experience evacuatory problems (mean +/- standard deviation evacuation score: 21.3 +/- 3.7 vs. 16.4 +/- 3.5, P < 0.001). Use of a pad was more frequent in the chemoradiation therapy than in the surgery alone group (53 vs. 18 percent, P = 0.02). The incidence after functional disorders was also more frequent in the irradiated group of patients: incontinence to gas (76 vs. 43 percent, P = 0.03), to liquid stool (64 vs. 25 percent, P = 0.01), and to solid stool (47 vs. 11 percent, P = 0.01). Moreover, irradiated patients reported more frequent pouch-related specific problems, such as clustering (82 vs. 32 percent, P = 0.001), and sensation of incomplete evacuation (82 vs. 32 percent, P = 0.001). Finally, regression analysis demonstrated that radiation-induced sphincter dysfunction was progressive over time. CONCLUSIONS: Both preoperative and postoperative chemoradiation therapy adversely affects continence and evacuation in patients with colonic J-pouch. Because radiation-induced damage to the normal tissues is known to be cumulative over time, long-term progressive dysfunction of the anal sphincter and neorectum are causes of concern. Consideration should be given to excluding the anal canal from the field of irradiation in patients with Stage II and III rectal cancer, whenever a sphincter-preserving procedure is planned.

Specialty versus generalist care of children with appendicitis: an outcome comparison.

BACKGROUND/PURPOSE: Some Health Maintenance Organizations (HMO) limit access of their members to specialists to lower costs. The purpose of this study is to determine whether this policy affects the outcome of children with appendicitis. METHODS: At a large academic medical center, children 17 years or younger with appendicitis were treated either by an HMO Adult General Surgical Service (group A) or a Pediatric Surgical Service (group B). Board certified pediatric surgeons were not available on the HMO surgical service. Anesthesia, surgical residents, nursing, and ancillary support services were identical in both groups. Study parameters included imaging tests performed, operation type, complications, readmissions, and length of stay. Results were analyzed using chi(2) and Fischer's Exact tests. RESULTS: One-hundred seventy-five consecutive children underwent appendectomy, 96 in group A and 79 in group B. In patients with simple acute appendicitis, there was no significant difference between group A and group B for complications, readmissions, second operation, or length of stay. In patients with gangrenous or perforated appendicitis there was a significant difference between group A and group B for type of operation (laparoscopic appendectomy, group A, 4 of 27 v. group B, 0 of 34; P =.04); complications (group A, 9 of 27 v. group B, 3 of 34; P =.025); readmissions (group A, 6 of 27 v. group B, 0 of 34; P =.001); second operation (group A, 6 of 27 v. group B, 2 of 34; P =.001); and mean total length of stay in days (group A, 8.6 of 27 v. group B, 5.4 of 34; P =.05). CONCLUSIONS: Children with significantly perforated appendicitis have lower complication rates and shorter lengths of hospital stay when treated by pediatric surgeons as compared with HMO adult general surgeons.

Converted laparoscopic colorectal surgery.

BACKGROUND: Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial. METHODS: A comprehensive search of the English-language literature was updated until May 1999. RESULTS: Twenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088), diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald chi-square value, p < 0.001). CONCLUSIONS: In nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Quantitative short-term study of anal sphincter function after chemoradiation for rectal cancer.

HYPOTHESIS: Pelvic irradiation adversely affects anal sphincter function after proctectomy with coloanal anastomosis for low rectal and middle rectal (<10 cm from the anal verge) tumors. DESIGN: Case-control study. SETTING: Private, tertiary care referral center. PATIENTS: Patients treated for low rectal adenocarcinoma between January 1, 1994, and October 31, 1999. INTERVENTIONS: Anal manometric data were prospectively collected at the time of initial diagnosis and before ileostomy closure. MAIN OUTCOME MEASURES: Mean and maximum resting pressures (RPs) and squeeze pressures, threshold volume for sensation, and maximal tolerable volume. RESULTS: Twenty-three patients in the surgery group and 19 in the chemoradiotherapy group were considered for analysis; 15 patients had preoperative radiotherapy and 4 had postoperative radiotherapy. At the time of ileostomy closure, RPs were significantly lower in the chemoradiotherapy group than in the surgery group (32.7 +/- 17 vs 45.3 +/- 18 mm Hg; P =.03). Squeeze pressures were not significantly different between the surgery and chemoradiotherapy groups (108.7 +/- 56.7 vs 102.0 +/- 52.6 mm Hg; P =.69). The ratios of postresection to preresection RPs were also significantly lower in the chemoradiotherapy group (0.49 +/- 0.29) than in the surgery group (0.76 +/- 0.22) (P =.005). Eight to 12 weeks after proctectomy with coloanal anastomosis, a 24% decrease in RP was noted in the surgery group. The addition of adjuvant pelvic irradiation decreased RP by another 27%. CONCLUSION: Adequate shielding of the anal sphincter should be performed for low rectal cancers whenever a sphincter-preserving procedure is considered.

P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy.

HYPOTHESIS: P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT). STUDY DESIGN: Retrospective analysis of p53 and Ki-67 status from the CRT arm of a randomized, controlled trial (n = 50) and from patients receiving the same treatment but not enrolled in the trial (n = 55). METHODS: P53 and Ki-67 status were established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells stained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained for Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive models were calculated for each outcome. RESULTS: Neither marker predicted tumor response to treatment. P53+ status was associated with tumor recurrence (P =.003) and locoregional recurrence (P =.003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free survival (P =.004), lower disease-specific survival (P =.04), lower overall survival with primary site preservation (P =.03), and lower disease-specific survival with primary site preservation (P =.003). Multivariate analysis revealed that p53+ status was significantly related to a lower recurrence-free survival (P =.01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P =.02, RR = 3.41). Ki-67+ status was not related to any variables. However, multivariate analysis revealed that Ki-67+ was significantly related to a lower overall survival (P =.05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associated with a lower incidence of tumor recurrence (P =.02), lower locoregional recurrence (P =.01), and fewer second primary lesions (P =.04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P =.02), higher disease-specific survival with primary site preservation (P =.02), and higher overall survival with primary site preservation (P =.02). Multivariate analysis revealed that p53-/Ki-67- status was significantly related to a higher overall survival with site preservation (P =.01, RR = 2.78). CONCLUSIONS: P53 and Ki-67 status appear to be related to the various survival end points considered in this study. However, this relation does not seem to be sufficient to warrant treatment modifications. Closer follow-up may be justified in both p53+ and Ki67+ patients to detect recurrence or a second primary at an earlier stage, possibly improving survival.

Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck.

BACKGROUND: The current study presents mature results from a Phase III randomized trial comparing radiation therapy and concurrent chemoradiotherapy in patients with resectable American Joint Committee on Cancer Stage III and IV disease. METHODS: One hundred patients were randomized to receive either radiation therapy alone (Arm A) (at a dose of between 66-72 grays [Gy] at 1.8-2 Gy per day) and the identical radiation therapy with concurrent chemotherapy (Arm B) (5-fluorouracil, 1000 mg/m(2)/day, and cisplatin, 20 mg/m(2)/day, both given as continuous intravenous infusions over 4 days beginning on Days 1 and 22 of the radiation therapy). Primary site resection was planned for patients with residual or recurrent local disease. Cervical lymph node dissection was performed for regional persistent disease or recurrence, or if N2-3 disease was present at the time of presentation. RESULTS: After completing all therapy including surgery, 82% of the patients in Arm A and 98% of the patients in Arm B had been rendered disease free (P = 0.02). At a median follow-up of 5 years (range, 3-8 years), the 5-year Kaplan-Meier projections for overall survival for Arm A versus Arm B were 48% versus 50% (P = 0.55). Kaplan-Meier projections for the recurrence free interval were 51% versus 62% (P = 0.04), projections for a distant metastasis free interval were 75% versus 84% (P = 0. 09), projections for overall survival with primary site preservation were 34% versus 42% (P = 0.004), and projections for local control without surgical resection were 45% versus 77% (P < 0.001). Salvage surgery proved to be successful in 63% and 73%, respectively, of the Arm A and Arm B patients with primary site failure. Unrelated death while free of disease occurred in 22% and 32%, respectively, of Arm A and Arm B patients (P = 0.26). CONCLUSIONS: The addition of concurrent chemotherapy to definitive radiation in patients with resectable Stage III and IV squamous cell carcinoma of the head and neck improves the likelihood of disease clearance, a recurrence free interval, and primary site preservation. However, overall survival does not appear to be improved, reflecting both effective surgical salvage after local recurrence and competing causes of death.

Sensitivity and specificity of the Braden Scale in the cardiac surgical population.

PURPOSE: A descriptive study was conducted to investigate the sensitivity and specificity of the Braden Scale for Predicting Pressure Ulcer Risk in a cardiac surgical population. PATIENTS AND SETTING: A convenience sample of 337 pressure ulcer-free patients undergoing cardiothoracic surgery at a large midwestern national referral center were enrolled in the study. METHODS: Systematic skin and Braden Scale assessments were completed independently on the day of surgery and on postoperative days 1, 3, and 5. The presence of a pressure ulcer was determined and classified using the 4-stage scale developed by the WOCN Society. RESULTS: Sixteen patients (4.7%) developed a total of 22 pressure ulcers. Sensitivity and specificity of Braden scores were calculated for the day of surgery and for postoperative days 1, 3, and 5. The established Braden "cutoff" score of < or = 16 to identify those "at risk" had poor specificity and sensitivity in this patient population. The appropriate cutoff score varied by hospital day. A preoperative Braden score of 22 correctly classified 50% of the pressure ulcer-positive patients. The appropriate cutoff scores on postoperative day 1, 3, and 5 were 13, 14, and 20, respectively. Those scores correctly classified 67% of the pressure ulcer-positive patients on postoperative day 1, 57% on postoperative day 3, and 50% on postoperative day 5. CONCLUSION: These results illustrate that optimum prediction of pressure ulcer risk can only be accomplished with reassessments and determination of the Braden cutoff score or scores that are reflective of the patient's changing clinical condition throughout the hospitalization.

Aggressive concurrent chemoradiotherapy for squamous cell head and neck cancer: an 8-year single-institution experience.

BACKGROUND: Since 1989, 105 patients with squamous head and neck cancer have been treated with combined chemoradiotherapy. OBJECTIVE: To examine the effectiveness of using combined chemoradiotherapy on patients with squamous head and neck cancer. DESIGN: Eight-year (1989-1997) single-institution evaluation of 105 patients. METHODS: Treatment consisted of fluorouracil, 1000 mg/m2 per day, and cisplatin, 20 mg/m2 per day, both given as continuous infusions during 4 days beginning on day 1 and 22 of a concurrent radiotherapy course. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Planned neck dissection was recommended for all patients with N2+ neck disease, irrespective of clinical response. RESULTS: The 105-patient cohort consisted of 79 men and 26 women. The primary site was identified in the oral cavity in 6, oropharynx in 46, larynx in 30, and hypopharynx in 20 patients. Two patients had multiple primaries and 1 patient had an unknown primary. There were 4 patients with stage II, 24 with stage III, and 77 with stage IV disease. Grade 3 and 4 chemoradiotherapy toxic effects included mucositis in 88% of patients, cutaneous reaction in 50%, neutropenia in 49%, thrombocytopenia in 12%, and nausea in 5%. There were no deaths secondary to treatment. The mean weight loss was 12% of initial body weight. To date, primary site persistence or recurrence has occurred in only 14 patients (13%). With a mean follow-up of 39 months, 66 patients (63%) are alive and free of disease. The Kaplan-Meier 4-year projected overall survival is 60% with a disease-specific survival of 74%, a distant metastasis-free survival of 84%, and an overall survival with primary site preserved of 54%. CONCLUSIONS: This chemoradiotherapy regimen, although toxic, is tolerable with appropriate supportive intervention. Locoregional and distant control are likely. Primary site conservation is possible in most patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancer.

Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.

Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.

The influence of scalp infiltration with bupivacaine on hemodynamics and postoperative pain in adult patients undergoing craniotomy.

UNLABELLED: After craniotomy, hypertension may contribute to intracerebral hemorrhage. We studied whether scalp infiltration with bupivacaine during craniotomy reduces postoperative pain and hypertension. In a double-blind fashion, 36 adult patients (ASA physical status II or III) undergoing elective craniotomy were randomly assigned to receive scalp infiltration with either bupivacaine (0.25%) and epinephrine (1:200,000) or saline/ epinephrine (1:200,000) for skeletal fixation, skin incision, and wound closure. Heart rate (HR) and mean arterial pressure (MAP) were measured after anesthesia induction, after skull-pin insertion, after scalp infiltration, during dural closure, during skin closure, on admission to postanesthesia care unit (PACU), and 1 h after admission. Visual analog pain scores were recorded in the PACU. MAP was significantly greater in the saline group at scalp infiltration. HR was significantly faster in the saline group at dural and skin closure. The bupivacaine group reported significantly less pain than the saline group at PACU admission and 1 h after admission. Pain scores did not correlate with hemodynamic measurements. We conclude that scalp infiltration with 0.25% bupivacaine with 1:200,000 epinephrine blunts certain intraoperative hemodynamic responses and reduces postoperative pain but has no effect on postoperative hemodynamics. IMPLICATIONS: We sought to evaluate whether scalp infiltration with bupivacaine and epinephrine at the beginning and end of craniotomy would afford more intra- and postoperative hemodynamic stability and influence immediate postoperative pain. We found that intraoperative hemodynamics were not influenced greatly; however, craniotomy patients do have significant postoperative pain, which does not seem to have an influence on hemodynamics in the postanesthesia care unit.

Progressive tricuspid valve disease in patients with congenitally corrected transposition of the great arteries.

BACKGROUND: The outcome of patients with corrected transposition of the great arteries (CTGA) is variably affected by associated intracardiac defects, tricuspid valve competence, and systemic right ventricular (RV) function. The relative importance of these factors in long-term outcome has not been evaluated. METHODS AND RESULTS: Since 1958, 40 patients with CTGA were studied to determine risk factors for poor outcome, including age, open heart surgery, tricuspid insufficiency (TI), cardiac rhythm, pulmonary overcirculation, and RV dysfunction. Follow-up ranged from 7 to 36 years (mean 20 years). Intracardiac repair was performed in 21 patients; 19 were unoperated or had closed heart procedures. For the purposes of this study the designation TI(S) refers to at least moderately severe TI as delineated by echocardiogram and/or angiography. TI(s) was the only independently significant factor for death (P=0.01), and in turn, only the presence of a morphologically abnormal TV predicted TI(s)(P=0.03). Twenty-year survival without TI(S)was 93%, but only 49% with TI(S). Poor long-term postoperative outcome was due to TI(S) in all but 1 patient; 20-year survival rates for operated patients with and without TI(s)were 34% and 90%, respectively (P=0.002). Similarly, 20-year survival rates for unoperated patients with and without TI(s)were 60% and 100%, respectively, whether or not attempts to repair the TI were made (P=0.08). CONCLUSIONS: TI(S)represents the major risk factor for CTGA patients; RV dysfunction appears to be almost always secondary to long-standing TI. Decisions related to surgical interventions with or without associated lesions must be strongly influenced by the status of the tricuspid valve.

A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis.

OBJECTIVE: To compare the tolerability and efficacy of two doses of i.v. methylprednisolone in patients with secondary-progressive MS. METHODS: I.v. methylprednisolone administered in high or low dose every other month for up to 2 years to 108 patients with secondary-progressive MS. RESULTS: No significant difference in efficacy with the primary outcome, a comparison of the proportions of patients in each treatment group who experienced sustained progression of disability. A relative treatment effect was detected with the high-dose regimen as measured by the preplanned secondary analysis, a comparison of time to onset of sustained progression of disability. Drug-related adverse events were observed more frequently in high-dose recipients but serious drug-related adverse events were uncommon, and cessation of study drug was only required in one patient. CONCLUSION: The results of the secondary analysis of this study suggest that a phase III trial of corticosteroids for secondary-progressive MS is warranted.

Results of 2-stage reimplantation for infected total knee arthroplasty.

Optimum treatment of the infected total knee arthroplasty has not been clearly established. To clarify the efficacy of two-stage reimplantation, experience with 66 infected total knee arthroplasties in 64 patients who had been treated with 2-stage reimplantation total knee arthroplasty between September 1980 and October 1993 was reviewed. Of these, 55 knees in 54 patients were available for follow-up examinations at an average of 61.9 months (range, 28-146 months). The initial diagnoses were rheumatoid arthritis (14 knees) and osteoarthritis (41 knees). Reimplantation was successful in 80.0% of knees with low-virulence organisms (coagulase-negative Staphylococcus, Streptococcus), 71.4% with polymicrobial organisms, and 66.7% with high-virulence organisms (methicillin-resistant Staphylococcus aureus). Reimplantation was successful in 82% of patients with osteoarthritis and in 54% of patients with rheumatoid arthritis (P = .024). The success rate was 92% if infection occurred after primary arthroplasty but only 41% if after multiple previous knee operations (arthroscopy, osteotomy, or revision total knee arthroplasty) (P < .001).