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Assessing the benefits of health research: lessons from research into the use of antenatal corticosteroids for the prevention of neonatal respiratory distress syndrome.

Do the benefits from health research justify the resources devoted to it? Addressing this should not only meet increasing accountability demands, but could also enhance understanding of research utilisation and how best to organise health research systems to increase the benefits. The process from basic research to eventual application and patient benefit is usually complex. The use of antenatal corticosteroids when preterm delivery is expected has featured large in the debates about research utilisation and provides an insight into these complexities. Based on an analysis of previous modelling of research utilisation and payback assessment, a framework is developed in which the existing literature on the use of corticosteroids, combined with new material developed by the authors, can be reviewed and synthesised. The move from animal studies to human trials was undertaken by the same individual. Some early clinical application of the findings occurred concurrently with a series of further trials. Nevertheless, the implementation of these findings stalled rather than accelerated as is predicted by some models. The eventual systematic review of the trials played a part in the development of the Cochrane Collaboration and increased the impact on practice. Further implementation approaches were used in various countries, including clinical guidelines, a National Institutes of Health Consensus Conference, and various implementation projects within the UK. This paper shows how an assessment of the benefits from this stream of research and utilisation projects can be constructed. It concludes that the application of a model for assessing payback can help to demonstrate the benefits from the research in this field and enhance our understanding of research utilisation.

Glucocorticoids↗

Pneumocystis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome.

The authors describe a patient with acquired immune deficiency syndrome (AIDS) who presented with an acute abdomen. A plaque-like tumor of the small intestine was resected and found to consist of masses of Pneumocystis carinii organisms. The organisms also exhibited a perivascular and intravascular distribution. Identical changes were found in regional lymph nodes. In addition to silver stains and electron microscopy, an immunohistochemical method for the demonstration of P. carinii was employed. The technique may have advantages over silver staining, as it identifies trophozoites in addition to cysts. A review of the literature concerning extrapulmonary pneumocystosis indicates that affected patients nearly always have concurrent pulmonary infection. The pattern of organ involvement and the finding of perivascular and intravascular organisms are consistent with lymphatic or hematogenous dissemination from the pulmonary focus. Pulmonary pneumocystosis was not documented in the patient described herein, although there were radiographic densities in one pulmonary lobe.

Acquired Immunodeficiency Syndrome↗

Comparison of surgical complications after organ-preservation therapy in patients with stage III or IV squamous cell head and neck cancer.

OBJECTIVE: To determine the incidence of minor and major complications in patients with squamous cell carcinoma of the upper aerodigestive tract who require surgical salvage or planned neck dissection after an initial treatment regimen with radiotherapy or concurrent chemoradiotherapy for organ preservation. DESIGN: The medical records of 100 patients treated in a phase 3 trial comparing radiotherapy alone with concurrent chemoradiotherapy for stage III and IV head and neck squamous cell carcinoma were reviewed. Fifty-four patients underwent 59 surgical procedures. Twenty-nine planned neck dissections were performed for persistent neck disease or initial stage N2 or greater. For persistent or recurrent disease at the primary site, 30 salvage operations were performed. SETTING: Academic tertiary care referral center. RESULTS: Complications occurred in 15 (46%) of the 33 procedures in the radiation-only group and 12 (46%) of the 26 procedures in the chemoradiotherapy group. Major complications occurred in 4 (12%) of the procedures in the radiation-only group and 3 (12%) of the procedures in the chemoradiotherapy group. The incidence of minor complications was 33% and 35% in the radiation-only and chemoradiotherapy groups, respectively. The major complication rate for salvage operations did not differ between the radiation-only and chemoradiotherapy groups (16% and 27%, respectively; P=.79 by chi2 test). The incidence of major complications in planned neck dissections was 7% of the radiation-only group and 0% of the chemoradiotherapy group. CONCLUSIONS: After radiation or concurrent chemoradiotherapy, surgery can be performed with an acceptable rate of major complications. Adding chemotherapy did not increase the incidence of surgical complications. These results differ from other reports in the literature.

Adult↗

Taxol plus radiation for head and neck cancer.

Taxol (paclitaxel) is the prototype of a new class of cancer drugs, the taxanes. This group of anticancer agents have a novel mechanism of action, broad clinical activity, and potential as clinical radiosensitizers. Paclitaxel may be the most efficacious single chemotherapy agent for head and neck cancer with a 40% response rate for patients with recurrent disease. As it is possible to achieve durable control with radiotherapy of locally advanced head and neck cancer in only a minority of cases, chemotherapy drugs such as paclitaxel are being used with radiotherapy in an attempt to improve tumor control. Paclitaxel stabilizes microtubules and leads to accumulation of cells at the G2/mitosis phase of the cell cycle, which is a necessary condition for its antitumor effect, and also the phase with the greatest relative radiosensitivity. Paclitaxel has been shown to be a radiosensitizer in vitro for some but not all cell lines studied. In vitro dose-response data for paclitaxel paradoxically suggest that prolonged exposure to relatively low concentrations--those easily achievable clinically--may be more effective than higher doses both for direct cytotoxicity and radiosensitization. These data suggest that paclitaxel has potential as a clinical radiosensitizer for head and neck cancer, and phase I trials are in progress. We review the laboratory and clinical studies supplying the rationale, risks, and potential benefits for the concurrent use of paclitaxel and radiotherapy, the current investigational clinical trials, including our NCI-sponsored phase I trials with continuous infusion paclitaxel as a potential radiosensitizer for head and neck cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents, Phytogenic↗

Effects of Medicaid drug utilization review intervention letters.

The state of Texas Drug Utilization Review (DUR) Board, composed of six physicians and six pharmacists, meets quarterly to determine criteria for implementing retrospective DUR. The board agreed to send intervention letters to physicians concurrently prescribing: (1) two histamine2 (H2)-antagonists (H2As) or (2) either any H2A or omeprazole with sucralfate. To measure the effect of these intervention letters, approximately half of these physicians were randomly chosen to receive a letter while the others served as a control group and did not receive letters. This project focused on the H2A or omeprazole with sucralfate intervention letters in a two-step process. Data on concurrent therapy involving two H2As were analyzed separately and these results are not included in this report. Objective one was to examine feedback from the physicians who received the letters, and objective two was to review and compare patient profiles 6 months after the letters were sent. Analysis of Medicaid prescription claims indicated that 190 physicians had concurrently prescribed either an H2A or omeprazole with sucralfate for 222 patients. Ninety-seven physicians (from 117 identified patient profiles) were selected to receive an intervention letter with their patient's profile or profiles, a response form, and a stamped envelope addressed to the Texas Department of Human Services. A 67.5% response rate was obtained. Of these responses, 49.4% agreed with the letter and 29.1% disagreed with the letter. The remaining indicated responses such as "not my patient," they were no longer seeing the patient, or that they did not prescribe the medication in question. (ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Bridging Organ-on-a-Chip and Omics: A Multi-Dimensional Frontier in Biomedical Research.

Organ-on-a-Chip (OOC) technology offers a powerful platform for replicating human tissue-specific microenvironments, thereby narrowing the translational gap between conventional biomedical models and actual human physiology. Concurrently, omics technologies deliver comprehensive molecular-level insights into biological systems. This review highlights the transformative potential of integrating OOC platforms with high-throughput omics methodologies. We systematically examine the classification, structural configurations, and engineering principles underlying OOC systems, alongside the defining attributes of key omics domains-genomics, transcriptomics, proteomics, and metabolomics. The convergence of dynamic OOC models with advanced omics technologies enables high-resolution, multi-dimensional analyses across numerous biomedical applications, including drug metabolism, disease mechanisms, environmental toxicity assessments, and host-microbiome interactions. This interdisciplinary integration is driving a paradigm shift in precision and translational medicine. However, several challenges remain to be addressed, such as the development of whole-organ mimetics, adaptation of sample collection techniques, and real-time artificial intelligence-based integration of biosensor data with multi-omics datasets. Addressing these hurdles will be vital for unlocking the full potential of this technological synergy in biomedical science.

Multiomics↗

Bifurcation stenting with drug eluting stents: illustration of the crush technique.

A number of percutaneous stenting techniques have been proposed for optimal treatment of bifurcation lesions. However, to date the most favorable interventional approach still remains controversial, since bifurcation lesions are associated with high procedural complication and restenosis rates. In the era of drug-eluting stents, crush stenting technique simplified the procedure, concurrently allowing full lesion coverage. The purpose of the present report is to review three cases treated with crush stenting and to describe in detail the technique and its variations.

Aged↗

Soft tissue masses in patients with multiple myeloma: a fine-needle aspiration study of 30 cases with flow cytometry and clinical correlation.

BACKGROUND: To the authors' knowledge, the prognostic significance of plasma cell cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and biopsies to assess plasma cell differentiation, tumor burden, and response to treatment. Monitoring of ST lesions by fine-needle aspiration (FNA) is not performed routinely. The objective of the current study was to examine ST masses in MM patients using FNA and to classify and determine the prognostic significance of MM in these lesions based on cytologic features. METHODS: FNAs of 30 ST masses from 27 patients with a history of MM were examined for disease involvement. In the patients with MM, the cytologic features were evaluated and the lesions were graded as low grade, intermediate grade, or high grade based on the classification of Bartl et al. for MM in BM specimens. Concurrent BM samples as well as cytogenetic and flow cytometric results also were reviewed. RESULTS: Twenty-seven of the FNA specimens (90%) were positive for MM, and three specimens (10%) were negative (one case each of lipoma, keratinous cyst, and aspergillosis). Among the MM cases, 5 (18.5%) were low grade, 15 (55.6%) were intermediate grade, and 7 (25.9%) were high grade (blastic MM). Simultaneous BM involvement was present in 23.5% of low-grade MM (4 of 17 cases), 35.3% of intermediate-grade MM (6 of 17 cases), and 71% of high-grade MM (5 of 7 cases). Clinically, 10 of 24 patients (42%) died within 9 months (median, 2 months). Patients with high-grade myeloma (blastic MM) in ST masses appeared to have worse survival; 43% (3 of 7 patients) died by a median time of 2 months, compared with 12% of patients with low-grade and intermediate-grade MM (2 of 17 patients). CONCLUSIONS: FNA of ST masses appears to improve the management of MM patients by providing diagnostic material, samples for ancillary studies, and prognostic information. ST MM can be classified reliably into grades of prognostic significance utilizing the classification of Bartl et al. Intermediate-grade MM was the most frequent subtype present in ST masses.

Adult↗

Reproducibility of the morphological diagnostic criteria for acute myeloid leukemia: the GIMEMA group experience.

Diagnostic reproducibility of the FAB morphological subtypes of acute leukemia is a basic step in the assessment of the clinical outcome in multicenter trials. Unusual cytologic variables and slightly different interpretations of the FAB morphological criteria have been the most significant factors affecting the overall diagnostic concordance rate among the various centers. An evaluation of the diagnostic concurrence between 35 institutions of the Italian Cooperative Study Group GIMEMA and two reviewers of the ad hoc morphological committee has been performed on 377 patients entering the AML 8A and AML 8B GIMEMA protocols. Overall concordance rate was 62.6%. The most significant differences were observed for M2 vs M4, M4 vs M5, M1 vs M2, and M2 vs M5 subtypes. In order to minimize the impact of some diagnostic deviations on the mean cytologic concordance rate, a distinction between "major" and "minor" discrepancies in the diagnostic procedures has been proposed. When the results of the single institutions were corrected by considering the "major" discrepancies only, a mean diagnostic agreement of 78.1% was reached.

Acute Disease↗

Relative carnitine deficiency in autism.

A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.

Adolescent↗

Surgical management of left main coronary artery aneurysm.

To date only 7 patients with left main coronary artery aneurysm associated with atherosclerosis have undergone surgical treatment. This report reviews a case of atherosclerotic aneurysm of the left main coronary artery with concurrent stenotic coronary artery disease that was successfully treated by direct approach to the left main coronary artery aneurysm and establishment of coronary artery bypass grafts.

Aged↗

Safety and efficacy of concomitant carotid and coronary artery operations.

BACKGROUND: Controversy exists concerning the best management for patients with concurrent severe carotid and coronary artery disease. METHODS: The records of 200 consecutive patients having concurrent carotid endarterectomy and coronary artery bypass grafting from 1979 to 1993 were reviewed, and follow-up was obtained (99% complete). Of the group (77% male; mean age, 67 years), 134 (67%) had unstable angina, 130 (65%) had triple-vessel disease, and 86 (43%) had left main coronary stenosis. Preoperative investigation revealed asymptomatic bruits in 116 (58%), transient ischemia in 65 (32%), strokes in 31 (16%), and bilateral carotid disease in 44 patients (22%). Nonelective operations were required in 66 patients (33%). RESULTS: Hospital death occurred in 7 patients (3.5%), myocardial infarction in 5 (2.5%), and permanent stroke in 6 (3%). Ten-year actuarial event-free rates were as follows: death, 58%; myocardial infarction, 81%; stroke, 92%; percutaneous angioplasty, 98%; redo coronary artery grafting, 94%; and all morbidity and mortality, 56%. Significant multivariate predictors of hospital death were postoperative stroke, failure to use an internal mammary artery graft, intraoperative intraaortic balloon, and nonelective operation. Significant predictors of postoperative stroke were peripheral vascular disease and unstable angina. Significant predictors of prolonged hospital stay were postoperative stroke, advanced age, and nonelective operation. CONCLUSIONS: Concomitant carotid endarterectomy and coronary bypass grafting can be performed with acceptably low operative risk and good long-term freedom from coronary and neurologic events.

Aged↗

Animal models for heat stroke studies.

Heat stroke is a medical emergency where quick diagnosis and management of victims are essential for positive prognosis. Several biochemical, physiological and hematological changes were observed in heat stroke. It seems that all of these changes are a consequence of induced tissue damage, or may have been a compensatory action by the body. Induction of hyperthermia and temperature measurement are important components in heat stroke studies to determine the stage of progression or regression of heat stroke. Several animal models have been established by investigators in heat related studies. Rats, dogs, monkeys, baboons, cows, rabbits, sheep and chicks have all been used in such studies that allow manipulation of exposure conditions and various designs of experiments. Amongst these species, rats, rabbits and sheep are the most suitable models because of their similarity to man in response to high temperature and in relation to their availability, cost and simplicity of handling. Such models may be used to study various pharmacological and biochemical parameters and functions concurrently. Further informations could also be obtained from isolated organ studies. The present review is to analyse and compare the available methodology for heat stroke studies.

Animals↗

Utility of post-transplant anti-HLA antibody measurements in pediatric cardiac transplant recipients.

BACKGROUND: Studies have associated anti-HLA antibodies detected by panel-reactive antibody (PRA) with increased risk for rejection and transplant coronary artery disease (TCAD) in adults, but the role of PRAs in monitoring immunologic status after pediatric cardiac transplantation has not been described. METHODS: We reviewed post-transplant PRAs in 96 pediatric heart recipients. PRAs were performed concurrently with endomyocardial biopsy and if rejection was suspected. The presence of anti-HLA IgG antibodies was defined as >10% reactivity. Pre-transplant variables, including age, race, gender, pre-transplant PRAs and presence of a mechanical assist device, were correlated with post-transplant PRAs. Outcome variables included rejection history, TCAD incidence and survival. RESULTS: The mean age of patients was 9.0 +/- 6.8 years. A mean of 8.1 +/- 5.3 PRAs were measured over a follow-up period of 4.8 +/- 2.7 years. There was a mean of 0.55 +/- 0.71 rejection events per patient-year, and TCAD was detected in 19 (22%) patients. Nineteen patients (20%) had anti-HLA Class I antibodies and 37 (39%) had Class II antibodies detected after transplant. There was no association between Class I antibodies and survival, TCAD or rejection. Class II antibodies were associated with worse survival and a decreased time-free of TCAD. Class II antibodies were also associated with rejection at the time of measurement (sensitivity 17%, specificity 94%) and for the ensuing 3 months (sensitivity 12%, specificity 94%). CONCLUSIONS: Class II anti-HLA antibodies correlate with worse patient outcomes and rejection episodes after pediatric cardiac transplant. A low sensitivity precludes use as a sole diagnostic tool, but post-transplant PRAs may be an important adjunct in a multi-faceted algorithm to assess immunologic status.

Adolescent↗

Treatment of asymptomatic carotid artery disease: similar early outcomes after carotid stenting for high-risk patients and endarterectomy for standard-risk patients.

BACKGROUND: The role of carotid angioplasty and stenting (CAS) in the treatment of asymptomatic patients with carotid disease remains controversial. The purpose of this report is to compare outcomes in asymptomatic patients treated with CAS and carotid endarterectomy (CEA). This was the initial experience performing CAS for most of the surgeons. For comparison, we also report our outcomes in standard-risk patients treated concurrently with CEA during the same period of time. METHODS: A retrospective, nonrandomized review of asymptomatic patients undergoing CEA or CAS at Washington University Medical Center in St. Louis was done. Patients with >70% asymptomatic carotid stenosis treated between September 2003 and April 2005 were identified. CEA was the first therapeutic consideration in all patients. CAS was reserved for high-risk patients. Thirty-day outcomes of stroke or death were recorded. During this time interval, 248 patients were treated including with 93 CAS and with 145 CEA. Symptomatic or clinically detected adverse outcomes such as myocardial infarction (MI), arrhythmia, renal failure, or pulmonary complications were noted but were not the primary end points of this review. This study addresses only the periprocedural outcomes of CEA and CAS in asymptomatic patients. No data >30-day follow-up are included. RESULTS: During this period, 93 CAS and 145 CEA procedures were done in asymptomatic patients. Patient characteristics in both groups were similar. Carotid protection devices were used in 91.4% of CAS patients. The results in the CAS group showed one death (1.1%) and one stroke (1.1%). In the CEA group, three strokes occurred (2.1%, P = 0.9999), one associated with death (0.7%, P = 0.9999). The CAS group had 1.34 +/- 0.83 risk factors vs 0.39 +/- 0.58 in the CEA group (P < .0001). Median CAS and CEA length of stay was 1 day. CONCLUSIONS: CAS for asymptomatic carotid stenosis demonstrated equivalent outcomes compared with CEA, despite CAS being reserved for use in a disadvantaged subset of high-risk patients owing to anatomic risk factors or medical comorbidities. These results suggest CAS should be considered a reasonable treatment option in the high-risk but asymptomatic patient. Enthusiasm for CAS should be tempered by the recognition that long-term outcomes in CAS-treated asymptomatic patients remain unknown.

Aged↗

Laryngotracheal separation for intractable aspiration pneumonia in neurologically impaired children: experience with 11 cases.

PURPOSE: Laryngotracheal separation (LTS) with or without end-to-side laryngoesophagostomy was performed as an antiaspiration procedure for intractable aspiration pneumonia in 11 children. The effectiveness of LTS for preventing aspiration was investigated. METHODS: Eleven children aged from 9 months to 16 years with intractable aspiration pneumonia underwent LTS with (n = 8) or without (n = 3) laryngoesophagostomy at our institution over the last 2 years. Of these 11 patients, 7 underwent fundoplication with or without gastrostomy for gastroesophageal reflux (GER) before LTS (n = 5) or concurrently with LTS (n = 2). The effectiveness of LTS was evaluated by chart review and follow-up phone questionnaires. RESULTS: LTS decreased the frequency of performing suction from an average of once every 30 minutes to once every 4.5 hours in all patients. In 5 patients who underwent fundoplication with gastrostomy before LTS, aspiration pneumonia remained unless they underwent LTS. Two patients who underwent LTS with or without laryngoesophagostomy tolerated oral feeding postoperatively. All parents rated LTS as excellent or good in terms of improving the quality of life. CONCLUSIONS: LTS can be recommended for neurologically impaired children with intractable aspiration as a primary surgical intervention. If patients show impaired swallowing and GER, LTS could be performed simultaneously with fundoplication and gastrostomy.

Adolescent↗

Survival in bilateral metachronous (asynchronous) Wilms tumors.

The survival of patients with Wilms tumors has improved dramatically during the last few decades. In contrast, the bilateral form of the disease, especially when the tumors are not concurrent, is still considered by many to hold a much worse prognosis. A review of 50 cases reported during the last 20 years reveals that the survival of patients with metachronous Wilms tumors has improved in parallel with survival of patients with unilateral disease and, when matched for extent of tumor spread, survivals for the last decade are almost identical to those of bilateral synchronous disease and unilateral Wilms tumors.

Child, Preschool↗

Chronic pain and posttraumatic stress disorder: mutual maintenance?

Common sequelae following a traumatic event include chronic pain and posttraumatic stress disorder (PTSD). Over the last decade, the literature relating to PTSD has become progressively more sophisticated, resulting in well-supported theories and treatments for sufferers. Equivalent research relating to chronic pain has more recently gathered momentum. However, to date there has been minimal attention devoted to the concurrence of the two disorders, even though high comorbidity has been noted. This review begins by briefly summarizing the literature relating to the two disorders in terms of symptoms, prevalence and comorbidity. It explicates the major psychological theories of chronic pain and PTSD and reviews the evidence relating what factors maintain the disorders. A number of pathways by which chronic pain and PTSD may be mutually maintaining are highlighted. We conclude that chronic pain and PTSD are mutually maintaining conditions and that there are several pathways by which both disorders may be involved in the escalation of symptoms and distress following trauma. Treatment implications are considered, as are issues for future research.

Adaptation, Psychological↗