Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

Blood pressure on arising, morning blood pressure surge and blood pressure variability in white coat hypertensives and in matched normotensives and sustained hypertensives.

INTRODUCTION: It is still controversial whether subjects with white-coat hypertension (WCHT) exhibit higher cardiovascular risk compared to normotensive subjects (NT). In subjects with WCHT it is not known whether the abnormal blood pressure (BP) reaction in the office also occurs at other times of day, particularly on arising and immediately after waking, i.e. the times at which the majority of cardiovascular events are reported to occur. OBJECTIVE AND METHODS: To evaluate with 24h ambulatory BP measurement the values of morning BP surge, BP on arising and BP variability in subjects with WCHT in comparison with age-, gender- and weight-matched normotensives (BP) and untreated sustained hypertensives (BP). RESULTS: Groups of BP, WCHT and BP were matched for age, gender and body weight: BP: n=69, age 49 +/- 7 years, 54 % female, BMI 26 +/- 1, casual BP 126/79 +/- 5/4 mmHg, daytime BP 124/80 +/- 6/6 mmHg; WCHT: n=74, age 52 +/- 8 years, 57% female, BMI 26 +/- 2, casual BP 152/95 +/- 7/7 mmHg, daytime BP 126/80 +/- 5/6 mmHg; HT: n=79, age 53 +/- 7 years, 56% female, BMI 27 +/- 2, casual BP 154/97 +/- 9/8 mmHg, daytime BP 143/89 +/- 12/10 mmHg. Of the three groups, subjects with WCHT exhibited BP on arising (121/81 +/- 13/8 mmHg) similar to that of NTs (120/80 +/- 13/9 mmHg, NS), both significantly lower than that of HTs (137/92 +/- 17/10 mmHg, p < 0.01), suggesting the absence of an alerting BP reaction in WCHT at that time. By contrast, subjects with WCHT showed higher values of systolic morning BP surge vs. NTs (25 +/- 10 vs. 22 +/- 11 mmHg, p < 0.05), both lower than that observed in hypertensives (33 +/- 11 mmHg, p < 0.01 vs. NT and WCHT) and greater daytime variability (systolic BP standard variation), i.e. 12 2 vs. 10 +/- 2 mmHg, p < 0.05, both lower than that observed in hypertensives (14 +/- 3 mmHg, p < 0.01 vs. NT and WCHT). CONCLUSIONS: Although subjects with WCHT did not show any alerting blood pressure reaction on arising, morning BP surge and BP variability were greater in these subjects than in control normotensives, although lower than sustained hypertensives. Although this is still speculative, we cannot exclude the possibility that even a slight increase in morning BP surge might in the long term constitute an additional load on the circulation that could increase cardiovascular risk in subjects with WCHT compared to matched normotensives.     

Cladribine therapy in refractory celiac disease with aberrant T cells.

BACKGROUND & AIMS: Refractory celiac disease (RCD) may be subdivided into RCD types I and II with phenotypically normal and aberrant intraepithelial T-cell populations, respectively. In RCD II, transition into enteropathy-associated T-cell lymphoma (EATL) is seen frequently. We have evaluated the effect of cladribine (2-CDA), a purine analogue inducing T-cell depletion, on clinical, histopathologic, and immunologic parameters, as well as the toxicity and side effects in a group of RCD II patients. METHODS: Between 2000 and 2005, 17 patients were included (8 men, 9 women). All patients had a clonal rearrangement of the T-cell receptor gamma gene and immunophenotyping showed an aberrant T-cell population lacking surface expression of CD3, CD8, and T-cell receptor alphabeta, in the presence of expression of surface CD103 and intracytoplasmic CD3. Treatment consisted of 2-CDA (0.1 mg/kg/day) intravenously for 5 days, given in 1-3 courses every 6 months depending on the response. RESULTS: All patients tolerated 2-CDA without serious side effects. Six patients (35.8%) showed a clinical improvement (weight gain, improvement of diarrhea, and hypoalbuminemia). In 10 patients (58.8%) a significant histologic improvement and in 6 patients (35.2%) a significant decrease in aberrant T cells was seen. Seven patients (41.1%) developed EATL and died subsequently. One patient died of progressive refractory state with emaciation. CONCLUSIONS: Treatment with 2-CDA in RCD II is feasible, well tolerated, and can induce clinical and histologic improvement as well as a significant decrease of aberrant T cells in a subgroup of patients, albeit it does not prevent EATL development. However, the earlier reported potential risk of precipitating an overt lymphoma should be taken into consideration.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.     

Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.

BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA radiation and measurement of plan quality using physical parameters in comparing conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison. Integral dose values were calculated. The ratios D50% (dose received by 50% of the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's volume) were calculated representing large volumes and small volumes of organs at risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA-TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body integral dose was higher for the CSA-TOMO plan by approximately 6.5%. CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis shows that tomotherapy improves dose ratios over conventional radiation for most organs at risk. The impact of a small increase in whole body integral dose is unknown. Long-term follow-up will be needed to answer this question as others have argued of the possibility of increased risk of secondary malignancies due to delivery of radiotherapy with IMRT.     

SPEECH EVALUATION WITH AND WITHOUT PALATAL OBTURATOR IN PATIENTS SUBMITTED TO MAXILLECTOMY

Most patients who have undergone resection of the maxillae due to benign or malignant tumors in the palatomaxillary region present with speech and swallowing disorders. Coupling of the oral and nasal cavities increases nasal resonance, resulting in hypernasality and unintelligible speech. Prosthodontic rehabilitation of maxillary resections with effective separation of the oral and nasal cavities can improve speech and esthetics, and assist the psychosocial adjustment of the patient as well. The objective of this study was to evaluate the efficacy of the palatal obturator prosthesis on speech intelligibility and resonance of 23 patients with age ranging from 18 to 83 years (Mean = 49.5 years), who had undergone inframedial-structural maxillectomy. The patients were requested to count from 1 to 20, to repeat 21 words and to spontaneously speak for 15 seconds, once with and again without the prosthesis, for tape recording purposes. The resonance and speech intelligibility were judged by 5 speech language pathologists from the tape recordings samples. The results have shown that the majority of patients (82.6%) significantly improved their speech intelligibility, and 16 patients (69.9%) exhibited a significant hypernasality reduction with the obturator in place. The results of this study indicated that maxillary obturator prosthesis was efficient to improve the speech intelligibility and resonance in patients who had undergone maxillectomy.     

Dentoskeletal treatment changes in Class II subdivision malocclusions in submentovertex and posteroanterior radiographs.

The objective of this study was to evaluate the dentoskeletal changes consequent to orthodontic treatment in subjects with Class II subdivision malocclusions, treated with asymmetric extractions, compared with a normal-occlusion control group. The sample consisted of 3 groups, with 30 subjects in each: normal-occlusion subjects (group 1), untreated Class II subdivision subjects (group 2), and Class II subdivision patients treated with asymmetric extractions (group 3). All subjects had a full complement of permanent teeth at the beginning of treatment. The average ages of the subjects were 22.42, 15.76, and 18.57 years, respectively, in groups 1, 2, and 3. Measurements of relative differences in the spatial position of dental and skeletal bilateral landmarks were obtained from the submentovertex and posteroanterior cephalometric (PA) radiographs. The t test for independent samples was used to compare group 1 with groups 2 and 3 at different times. Results from the submentovertex radiograph showed that asymmetric extractions in Class II subdivision malocclusions will maintain the differences in the anteroposterior positions of right and left, maxillary and mandibular first molars, as would be expected with the treatment protocols used. There were no significant skeletal changes that could be attributed to the treatment approaches investigated or transverse collateral effects with the asymmetric mechanics used. It was also demonstrated that treatment of Class II subdivision malocclusions with asymmetric extractions produced corrections of maxillary and mandibular dental midline deviations with the midsagittal plane, without canting the occlusal plane or any other investigated horizontal plane, as seen in the PA radiograph. Treatment of Class II subdivision malocclusions with asymmetric extractions constitutes a beneficial approach to this problem.     

Early symptoms in the prodromal phase of delirium: a prospective cohort study in elderly patients undergoing hip surgery.

OBJECTIVES: The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery. METHODS: This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium. RESULTS: Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium. CONCLUSIONS: Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.