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Integrating quantitative and qualitative methodologies for the assessment of health care systems: emergency medicine in post-conflict Serbia.

BACKGROUND: Due to the complexity of health system reform in the post-conflict, post-disaster, and development settings, attempts to restructure health services are fraught with pitfalls that are often unanticipated because of inadequate preliminary assessments. Our proposed Integrated Multimodal Assessment - combining quantitative and qualitative methodologies - may provide a more robust mechanism for identifying programmatic priorities and critical barriers for appropriate and sustainable health system interventions. The purpose of this study is to describe this novel multimodal assessment using emergency medicine in post-conflict Serbia as a model. METHODS: Integrated quantitative and qualitative methodologies--system characterization and observation, focus group discussions, free-response questionnaires, and by-person factor analysis--were used to identify needs, problems, and potential barriers to the development of emergency medicine in Serbia. Participants included emergency and pre-hospital personnel from all emergency medical institutions in Belgrade. RESULTS: Demographic data indicate a loosely ordered network of part-time emergency departments supported by 24-hour pre-hospital services and an academic emergency center. Focus groups and questionnaires reveal significant impediments to delivery of care and suggest development priorities. By-person factor analysis subsequently divides respondents into distinctive attitudinal types, compares participant opinions, and identifies programmatic priorities. CONCLUSIONS: By combining quantitative and qualitative methodologies, our Integrated Multimodal Assessment identified critical needs and barriers to emergency medicine development in Serbia and may serve as a model for future health system assessments in post-conflict, post-disaster, and development settings.

Attitude of Health Personnel↗

Relationship between magnetic resonance arterial patency and perfusion-diffusion mismatch in acute ischemic stroke and its potential clinical use.

BACKGROUND: In patients with acute ischemic stroke the magnetic resonance (MR) perfusion-diffusion mismatch pattern (perfusion lesion at least 20% larger than the lesion on diffusion-weighted imaging) may indicate ischemically threatened but viable tissue. To our knowledge, the relationship of this MR pattern to serial changes in MR angiography (MRA) has not been reported. OBJECTIVES: To investigate the relationship between MRA changes and patterns of diffusion-weighted imaging and perfusion abnormalities and to determine if the information obtained could be used in clinical management. METHODS: The MR studies of 35 patients who had undergone sequential multimodality MR imaging studies within the first 4 days of stroke were reviewed. All lesions were in the internal carotid artery territory distribution. Magnetic resonance angiographies were read by 2 observers blinded to the clinical data. RESULTS: During the first 24 hours a perfusion-diffusion mismatch was present in 22 (92%) of the 24 patients with an MRA arterial occlusive lesion. (At this time 5 [46%] of the 11 patients with a normal MRA [P =.006] also had a mismatch.) Two to 4 days after stroke, of these 22 patients resolution of the mismatch occurred in 8 (87%) of 9 patients with recanalization on MRA compared with 5 (39%) of 13 patients without arterial recanalization (P =.03). Resolution of mismatch occurred in 3 (60%) of 5 patients with a normal MRA and a mismatch at the first time point. CONCLUSIONS: Concordance between MRA and the MR perfusion-diffusion mismatch pattern provides supportive evidence for an arterial vascular basis for this MR signature in acute stroke. Discordance between MRA lesions and mismatch may result from arterial branch occlusions undetected by MRA or from an alternate mechanism for the mismatch. The MR imaging patterns identified extend our understanding of the pathophysiology of stroke and may contribute to the improvement of stroke management in the future.

Acute Disease↗

Maternal antigen avoidance during lactation for preventing atopic disease in infants of women at high risk.

OBJECTIVES: To assess the effects of prescribing an antigen avoidance diet during lactation on the nutritional status of the mother and newborn and on the development of atopic disease in the child. The main focus is on women whose infants are at high risk for developing an atopic condition, based on a history of atopic disease in the mother, father, or a previous child. SEARCH STRATEGY: The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. SELECTION CRITERIA: All acceptably controlled comparisons of maternal antigen avoidance prescribed to lactating women at high risk, regardless of the degree of antigen avoidance (number of foods eliminated from the diet) or its duration. Trials of multimodal interventions that include manipulation of the infant's diet other than breast milk or of other nondietary aspects of the infant's environment (eg, exposure to inhaled allergens) have been excluded from the review. DATA COLLECTION AND ANALYSIS: Data were extracted by the author from published reports, and supplemented by additional information from trialists contacted by the author. MAIN RESULTS: Three trials involving 209 women were included. The combined data from the three available trials suggest a strong protective effect of maternal antigen avoidance on the incidence of atopic eczema during the child's first 12-18 months of life. Methodologic shortcomings in all three trials, however, argue for caution in applying these encouraging results. In particular, the high incidence of atopic eczema in the control groups of all three trials might be explained by nonblinding or de-blinding of the examining physicians. REVIEWER'S CONCLUSIONS: Prescription of an antigen avoidance diet to a high-risk woman during lactation may substantially reduce her child's risk of developing atopic eczema, but better trials are needed.

Dietary Proteins↗

Role of operculoinsular cortices in human pain processing: converging evidence from PET, fMRI, dipole modeling, and intracerebral recordings of evoked potentials.

Insular and SII cortices have been consistently shown by PET, fMRI, EPs, and MEG techniques to be activated bilaterally by a nociceptive stimulation. The aim of the present study was to refer to, and to compare within a common stereotactic space, the nociceptive responses obtained in humans by (i) PET, (ii) fMRI, (iii) dipole modeling of scalp LEPs, and (iv) intracerebral recordings of LEPs. PET, fMRI, and scalp LEPs were obtained from normal subjects during thermal pain. Operculoinsular LEPs were obtained from 13 patients using deep brain electrodes implanted for presurgical evaluation of drug-resistant epilepsy. Whatever the technique, we obtained responses which were located bilaterally in the insular and SII cortices. In electrophysiological responses (LEPs) the SII insular contribution peaked between 150 and 250 ms poststimulus and corresponded to the earliest portions of the whole cerebral response. Group analysis of PET and fMRI data showed highly consistent responses contralateral to stimulation. On single-subject analysis, LEPs and fMRI activations were concentrated in relatively restricted volumes even though spatial sampling was quite different for both techniques. Despite our multimodal approach, however, it was not possible to separate insular from SII activities. Individual variations in the anatomy and function of SII and insular cortices may explain this limitation. This multimodal study provides, however, cross-validated spatial and temporal information on the pain-related processes occurring in the operculoinsular region, which thus appears as a major site for the early cortical pain encoding in the human brain.

Adult↗

Multidisciplinary approach to esophageal and gastric cancer.

Despite marked advances in surgical therapy for patients with esophageal, esophagogastric, and gastric cancers, the overall prognosis of these patients has not markedly improved during the past decades. Multidisciplinary approaches using adjuvant postoperative and neoadjuvant preoperative therapeutic principles have received increasing attention with regard to the management of these patients. A series of randomized, prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in esophageal, esophagogastric junction, or gastric cancer. The available data on the role of neoadjuvant preoperative therapy are not yet conclusive. Although neoadjuvant therapy may reduce the tumor mass in many patients, several randomized, controlled trials have shown that, compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, that is, potentially resectable, tumors. In contrast, in patients with locally advanced tumors, that is, patients in whom complete tumor removal with primary surgery seems unlikely, neoadjuvant therapy increases the likelihood of complete tumor resection on subsequent surgery, but only patients with objective histopathologic response to preoperative therapy seem to benefit from this approach. Consequently, in the future, improvements in the overall survival of patients with esophageal, esophagogastric junction, or gastric cancer most likely will be achieved only by tailored therapeutic strategies that are based on the individual tumor location, tumor stage, and consideration of established prognostic factors. A clear classification of the underlying tumor entity, a profound knowledge of the prognostic factors applicable, a thorough preoperative staging, and identification of parameters that allow for the prediction of response to preoperative therapy will become essential for the selection of the optimal therapeutic modality for individual patients.

Adenocarcinoma↗

Multimodality functional imaging evaluation in a patient with Rasmussen's encephalitis.

Rasmussen's encephalitis (RE) is a cryptogenic progressive inflammatory disorder of the brain that causes severe neurological problems, including intractable focal epilepsy. In select patients, aggressive treatment using cerebral hemispherectomy may ameliorate the devastating cognitive decline that accompanies this disease, even if the epileptic focus appears broadly distributed. We present a case of histopathologically-confirmed RE evaluated using a multimodal process that explored the physical and functional aspects of the associated epilepsy. This process included magnetic resonance imaging, single photo emission computed tomography, electroencephalography, and magnetoencephalography (MEG). The findings indicate that functional brain imaging data may greatly assist the surgical treatment decision-making process in RE, especially when structural imaging fails to reveal definitive localizing information. In addition, MEG may provide insights about the cortical reorganization of somatosensory cortex following hemispherectomy.

Child↗

Quantitative DNA analysis of an intracerebrally transplanted brain tumour model after experimental chemotherapy with BCNU and CCNU.

In the present study we investigated the susceptibility of high passages of the rat glial transplantation tumour G-XIII to chemotherapy using nitrosourea compounds. We observed a significant increase in lifespan (ILS) of animals treated with BCNU (37%, p < 0.01) and CCNU (27%, p < 0.01). There were no difference in the efficiency between these two substances. Using a semi-quantitative score system no histopathological changes were observed which were associated with the response to therapy. The only predicative parameter in the present study was the quantitative DNA distribution pattern. There was a close correlation between treatment and the occurrence of unimodal DNA distribution patterns indicating clonal regrowth of recurrent tumours. Moreover, we also observed a correlation of the DNA distribution pattern of recurrent tumours with the result of experimental chemotherapy. Survival times of animals suffering from tumours containing unimodal DNA histogram was significantly longer than survival times of rats with multimodal DNA distribution, i.e. bimodal or broad DNA histograms. A unimodal, near-diploid stem line was only present in treated animals suggesting that these clones are more resistant against therapy using nitrosourea compounds. Our data indicate DNA cytophotometry as comprehensive tool for the monitoring of therapy response and the design of experimental chemotherapy using rat glial tumours.

Animals↗

Multimodal homesickness prevention in boys spending 2 weeks at a residential summer camp.

Homesickness is the distress or impairment caused by an actual or anticipated separation from home. It is characterized by preoccupying thoughts of home and attachment objects. In its severe form, homesickness is subjectively distressing and has clinically significant cognitive, emotional, and behavioral sequelae. This study provided 75 boys who ranged in age from 8 to 16 years and who were 1st-year campers at an overnight summer camp with an inexpensive, multimodal homesickness prevention package. Results suggest that combining environmental information, psychoeducation, social support, explicit coping instruction, caregiver education, practice time away from home, and surrogate caregiver training can reduce homesickness and associated behavior problems. These data support the theory that novelty reduction, attitudinal shifts, preseparation coping enhancement, and supportive social environments diminish the negative emotional intensity of homesickness.

Adaptation, Psychological↗

Neoadjuvant strategies for prostate cancer prior to radical prostatectomy.

Although definitive therapy with either radical prostatectomy or radiation therapy can be effective, the optimal treatment for prostatic adenocarcinoma remains controversial. Patients may be at significant risk for primary treatment failure even with apparent clinically localized disease. Thus, there has been increased interest in initial multimodal therapy in order to maximize the potential for cure. Neoadjuvant hormonal therapy prior to radical prostatectomy has been used for several decades and a large body of literature discusses its use; nevertheless, the current data suggest that it only decreases rates of positive surgical margins without improving prostate-specific antigen (PSA)-free or disease-free survival. Novel neoadjuvant hormonal and chemotherapeutic regimens are under investigation and may improve outcomes for patients undergoing radical prostatectomy.

Adenocarcinoma↗

Multimodality correlative study of canine brain tumors. Proton magnetic resonance spectroscopy, positron emission tomography, and histology.

RATIONALE AND OBJECTIVES: Structural/functional relationships in an induced canine brain tumor were studied using proton-magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), and histology. METHODS: Proton-MRS and PET data of implanted canine brain tumors were correlated with quantitative analysis of the tissue composition within the MRS and PET regions of interest (ROIs). Linear regression analysis was employed to correlate the 1H-MRS and PET data with the percent tumor and the percent total lesion (comprising tumor plus associated pathology ie, edema, cysts, hemorrhage, inflammation) within the ROI. RESULTS: Using 1H-MRS, N-acetyl aspartate concentrations were indirectly correlated with the amount of tumor (P = .058), as well as the amount of tumor plus associated pathology (P = .032) within the ROI. Total creatine concentrations were indirectly correlated with the amount of tumor and the amount of tumor plus associated pathology within the ROI (P < .05). Lactate concentrations were directly correlated with the amount of tumor (P = .053) and the amount of tumor plus associated pathology (P = .058) within the ROI. Using PET, Oxygen metabolic rates were indirectly correlated with the amount of tumor and with the amount of tumor plus associated pathology within the ROI (P < .05). Glucose metabolic rates were directly correlated with both the amount of tumor and with the amount of tumor plus associated pathology at P < .05. Proton-MRS measured concentrations of choline and PET measured values for blood flow, and oxygen extraction showed correlations with the amount of tumor and with the amount of tumor plus associated pathology at P > or = .08. CONCLUSIONS: The PET and MRS data were complementary with respect to suggesting anaerobic glucose metabolism for the tumor. Unlike other tumors, no increase in choline was noted in the canine tumor.

Animals↗

Multimodality Bayesian algorithm for image reconstruction in positron emission tomography: a tissue composition model.

The use of anatomical information to improve the quality of reconstructed images in positron emission tomography (PET) has been extensively studied. A common strategy has been to include spatial smoothing within boundaries defined from the anatomical data. We present an alternative method for the incorporation of anatomical information into PET image reconstruction, in which we use segmented magnetic resonance (MR) images to assign tissue composition to PET image pixels. We model the image as a sum of activities for each tissue type, weighted by the assigned tissue composition. The reconstruction is performed as a maximum a posteriori (MAP) estimation of the activities of each tissue type. Two prior functions, defined for tissue-type activities, are considered. The algorithm is tested in realistic simulations employing a full physical model of the PET scanner.

Algorithms↗

A model for simultaneous study of pressure and electric events in the rabbit sphincter of Oddi and duodenum.

An animal experimental model featuring simultaneous recordings of electromyography and pressure from the sphincter of Oddi (SO) and duodenum is demonstrated. On the basis of data from 10 rabbits, pressure recordings from the SO were shown to have phasic activity with an average basic pressure peak interval of 2.6 to 3.5 sec. Histographic analysis of SO pressure recordings showed a multimodal appearance, suggesting that the activity is paced. A substantial amount of overlap between SO and duodenal contractions was observed. As many as 30% of the pressure peaks recorded from the SO could not be assigned to a spike complex in the corresponding EMG tracings. It is suggested that combined recordings of EMG and pressure activity are needed to characterize fully the motility of the SO and duodenum.

Ampulla of Vater↗

Comparisons of three alternative breast modalities in a common phantom imaging experiment.

Four model-based imaging systems are currently being developed for breast cancer detection at Dartmouth College. A potential advantage of multimodality imaging is the prospect of combining information collected from each system to provide a more complete diagnostic tool that covers the full range of the patient and pathology spectra. In this paper it is shown through common phantom experiments on three of these imaging systems that it was possible to correlate different types of image information to potentially improve the reliability of tumor detection. Imaging experiments were conducted with common phantoms which mimic both dielectric and optical properties of the human breast. Cross modality comparison was investigated through a statistical study based on the repeated data sets of reconstructed parameters for each modality. The system standard error between all methods was generally less than 10% and the correlation coefficient across modalities ranged from 0.68 to 0.91. Future work includes the minimization of bias (artifacts) on the periphery of electrical impedance spectroscopy images to improve cross modality correlation and implementation of the multimodality diagnosis for breast cancer detection.

Breast Neoplasms↗

The dynamics of neuronal dysfunction and recovery following severe head injury assessed with serial multimodality evoked potentials.

Serial studies of visual, auditory, and somatosensory evoked potentials (EP's) obtained from 139 severely head-injured patients up to 1 year after trauma were analyzed to ascertain whether or nor EP's can be used to monitor neurological recovery or deterioration following secondary insults. The EP data were analyzed using a grading system of abnormality developed previously, and patients were grouped by the most severe EP abnormality found in any modality during an early study (mean Day 3). The findings showed differential recovery trends depending on the severity of EP abnormality obtained on the initial study and presence of secondary insult. If EP's were normal early after injury, they remained so for up to 1 year, and these patients did well clinically. The EP's that were absent did not improve, and the patients had poor outcomes. Secondary insults did not affect the EP's or the outcomes of patients in these two groups. When EP's that were initially mildly abnormal became normal or remained no worse than mildly abnormal, patients had favorable outcomes in spite of complications. In contrast, deterioration of EP's with secondary insult indicated poor patient outcome. Severe EP abnormalities which improved over time led to favorable outcomes. However, persistence or deterioration of severe abnormalities indicated a poor outcome. Changes in EP's over time were better indicators of outcome than the presence or absence of complications. The results suggest that EP's may be used to assess neural recovery and the consequences of secondary insults to the brain. Four case reports are included to exemplify results.

Adolescent↗

Combined modality treatment for central nervous system malignancies.

This review summarizes the current status and future prospects for combined modality treatment of primary and metastatic central nervous system malignancies. The laboratory and clinical basis for multimodality therapy, including surgery, ionizing radiation, and drug therapy, are outlined and critically reviewed. The central nervous system diseases discussed include: glioma (low and high grade), brain metastases, and primary central nervous system lymphoma. Collectively, these data suggest a shift favoring combined modality approaches in several of these diseases; however, the incremental gains are indeed modest. The individual practitioner must weigh these with the additional toxicities before making a therapeutic decision for a particular patient. The future direction of combined modality therapy in these diseases will likely revolve around the increased use of molecular diagnostics resulting in the application of targeted therapy. Clearly, such promising innovations must be delineated in the context of continued preclinical studies and controlled clinical trials.

Adult↗

Delay analysis in the auditory brainstem of the rat: comparison with click latency.

Many cells in the auditory brainstem 'phase lock' to tone stimuli. From the changing phase relationship between the stimulus and the neural response in phase-locking cells, the delay between them can be estimated. This delay, however, is consistently greater than the latency measured in response to click stimuli, an important discrepancy. In this paper the different measures of delay, namely phase delay, group delay and signal-front delay are re-examined. An improved method for computing the average group delay is presented, which accounts for the cyclical nature of the phase data. Data were collected from units in successive processing sites of auditory pathway: the auditory nerve, the cochlear nucleus, the trapezoid body and the medial nucleus of the trapezoid body. Low-characteristic frequency (CF) units gave multimodal post-stimulus-time histograms in response to clicks, and showed stepwise decreases in latency with increasing intensity, with the appearance of earlier peaks in the response, rather than shifts in the timing of the peaks. The separation of peaks corresponded to the inverse of the unit's CF. High-CF units also showed a decline in click latency with intensity, but to a lesser degree than low CF units. We present an analysis which explains the difference between click latency and delay, and which in contrast to previous accounts is experimentally testable. We demonstrate that this new framework accounts for the discrepancy between the two measures of delay, and in addition accounts for the observed stepwise shifts in click latency for low-CF units.

Acoustic Stimulation↗

Perioperative pain control.

There are many options for perioperative pain control available to surgeons. Given these options, adequate levels of analgesia should be achieved and maintained in all surgical patients. Data suggest that analgesia may be improved by combining different analgesic approaches. To avoid high-dose requirements, dose-dependent adverse effects, and potential toxicity associated with reliance on one agent or technique, "balanced" or multimodal analgesic regimens have been advocated. A multimodal recovery program consists of three major components: (1) early mobilization, (2) complete perioperative analgesia, and (3) early oral nutrition. The goal of multimodal programs is to accelerate patient rehabilitation and reduce hospital stays. Balanced multimodal programs are the present and future of perioperative pain control and will enhance patient care.

Analgesia↗

Intraoperative radiotherapy in the multimodality approach to gastric cancer.

It is difficult to conclude a clear benefit from the addition of IORT to the multimodality treatment of gastric cancer based on the studies available. Only three prospective randomized trials have been published and each varies in the approach of combining adjuvant and neoadjuvant chemotherapy and EBRT with IORT. With a complex degree of confounding factors in these and other retrospective series, it also remains difficult to identify a decrease in local recurrence rates, or an improvement in overall patient survival rates attributable to the use of IORT. Several series, however, have identified patient subsets--specifically, patients who have advanced disease with serosal extension or node-positive disease--who may be more likely to benefit from the addition of IORT to gastric resection. Finally, there is no evidence in prospective or retrospective series that there is an increased patient risk or inferior outcome caused by the addition of IORT. Limited evidence of a possible benefit in advanced disease and no evidence of a disadvantage to the use of IORT have promoted continued use and investigation in the multimodality treatment of an aggressive disease. Continued efforts in prospective randomized trials should be promoted to further delineate the efficacy of IORT and EBRT in the treatment of gastric cancer, especially in light of recently published data [30], where concurrent chemotherapy has been reported to increase survival rates in high-risk patients.

Adenocarcinoma↗