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PubMed1993

Probing the effects of individual components in multiple component prevention programs.

Assessing the contributions of individual components in multi-component interventions poses complex challenges for prevention researchers. We review the strengths and weaknesses of designs and analyses that may be useful in answering three questions: (1) Is each of the individual components contributing to the outcome? (2) Is the program optimal? and (3), Through what processes are the components of the program achieving their effects? Factorial and fractional factorial designs in which a systematically selected portion of all possible treatment combinations is implemented are used to address question 1. Response surface designs in which each component is quantitatively scaled are explored in relation to question 2. Mediational analysis, a hybrid of experimental and correlational approaches, is considered in relation to question 3. Design enhancements are offered that may further strengthen some of these techniques. These techniques offer promise of enhancing both the basic science and applied science contributions of prevention research.

Combined Modality Therapy↗
PubMed2004

Dependence of positive effects of granulocyte colony-stimulating factor on the antibiotic regimen: evaluation in rats with polymicrobial peritonitis.

We tested the hypothesis that the ability of granulocyte colony-stimulating factor (G-CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose-response curve that was sensitive to antibiotic prophylaxis. G-CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G-CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G-CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro-inflammatory cytokine release (tumor necrosis factor-a, interleukin-6, macrophage inflammatory protein-2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G-CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G-CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here.

Animals↗
PubMed1999

[r-tPA in keratoplasty à chaud. Report of 50 patients].

BACKGROUND: Fibrinolytic treatment using recombinant plasminogen activator (r-tPA) has been reported in cataract surgery; however, reports are lacking with respect to complex surgical interventions including keratoplasty because of anterior segment infections. PATIENTS AND METHODS: This report deals with a prospective study comprising 50 patients (50 eyes) suffering from a serpent ulcer treated by keratoplasty à chaud. r-tPA (25 micrograms) was instilled intracamerally at the end of surgery in 25 eyes. RESULTS: The 25 eyes treated with r-tPA were subsequently less inflamed than the control population (decrease in inflammatory cells 1.5 days vs 7 days, fibrin reaction 1x vs 12x), had highly significantly better visual acuity and there was significantly reduced inpatient hospitalization (median 9.9 vs 19.3 days). No hemorrhages were observed in either population; medically treated infection recurrences (S. aureus, C. tropicalis, acanthameba) were observed in 3 and primary graft failure or rejection in both populations 3x. CONCLUSIONS: This study showed that perioperative application of r-tPA had a beneficial effect. This therapeutic avenue should be further evaluated in a randomized, double-masked multicenter study.

Adolescent↗
PubMed2003

[Evaluating the first German diagnosis-related groups (G-DRG) in cardiological patients: problems in the correct medical and economic grouping].

About three years ago, the German Government initiated a complete change in the reimbursement system for costs of the in-hospital treatment of patients. A commission of representatives from every component of the German health system decided to adapt the Australian refined Diagnosis Related Groups (AR-DRG system). The AR-DRG system was selected as it would fit best to the German system and because of its high flexibility and preciseness reflecting severity of diseases and treatments. In October 2002, the first German Diagnosis Related Groups (G-DRGs) were calculated from the data of about 116 hospitals. These data now allow first analyses in how far a correct and precise grouping of patients in specific hospital settings is indeed performed and corresponds to the actual costs. Thus, we thoroughly calculated all costs for material and personnel during the in-hospital stay for each patient discharged during the first 4 months of 2002 from our cardiological department. After performing the grouping procedure for each patient, we analyzed in how far inhomogeneous patient distribution in the DRGs occurred and which impact this had on costs and potential reimbursements. Several different problems were identified which should be outlined in this work regarding three G-DRGs: costs of patients who received an implantable cardioverter defibrillator (F01Z) were markedly influenced by multimorbidity and additional expensive interventions which were not reflected by this G-DRG. Use of numerous catheters and expensive drugs represented a major factor for costs in patients with coronary angioplasty in acute myocardial infarction (F10Z) but seemed to be not sufficiently included in the cost weight. A specific area of patient management in our department is high frequency ablation of tachyarrhythmias which is included in other percutaneous interventions (F19Z). Complex procedures such as ablation of ventricular tachycardia or new innovative procedures as ablation of atrial fibrillation were associated with high costs leading to inadequate reimbursement. Furthermore, problems in the associated codes for diseases and procedures became apparent. Opportunities for future optimization such as specific new DRGs, splitting of DRGs, or the impact of changes in reimbursement for high-outliers were discussed.

Angioplasty, Balloon↗
PubMed2005

Splenic rupture complicating periinterventional glycoprotein IIb/IIIa antagonist therapy for myocardial infarction in polycythemia vera.

Polycythemia vera is a myeloproliferative disorder predisposing to thromboembolic and bleeding complications. We report the case of a patient with polyglobuly, leukocytosis, and thrombocytosis, who suffered from acute ST-segment elevation myocardial infarction due to thrombotic high-grade pre-stent stenosis two months after percutaneous coronary intervention for complex coronary one vessel disease. Following re-PTCA and stent implantation in conjunction with periinterventional GP IIb/IIIa antagonist treatment, the patient was initially symptom free for about two hours before rapidly developing signs of a hemorrhagic shock. An abdominal CT scan showed splenic rupture with massive intraabdominal hemorrhage as a consequence of secondary bleeding into multiple pre-existing splenic infarctions. The patient's condition stabilized after emergency splenectomy. Subsequent bone marrow biopsy revealed the presence of polycythemia vera. Post-operatively, the patient was treated with the anti-platelet agents aspirin and clopidogrel to prevent subacute stent thrombosis. Additionally, cyto-reductive therapy with hydroxyurea was initiated because of a further increase in the platelet count. In patients with polycythemia vera, the indication for treatment with GP IIb/IIIa antagonists should be carefully weighed against the potentially serious bleeding complications. Should treatment be established, a risk stratification using abdominal sonography and bleeding time testing is recommended, while during treatment red blood count, platelet count, coagulation tests, and hemodynamic parameters should be closely monitored.

Abciximab↗
PubMed1998

Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus.

Cells of Catharanthus roseus (L.) G. Don were genetically engineered to over-express the enzymes strictosidine synthase (STR; EC 4.3.3.2) and tryptophan decarboxylase (TDC; EC 4.1.1.28), which catalyze key steps in the biosynthesis of terpenoid indole alkaloids (TIAs). The cultures established after Agrobacterium-mediated transformation showed wide phenotypic diversity, reflecting the complexity of the biosynthetic pathway. Cultures transgenic for Str consistently showed tenfold higher STR activity than wild-type cultures, which favored biosynthetic activity through the pathway. Two such lines accumulated over 200 mg.L-1 of the glucoalkaloid strictosidine and/or strictosidine-derived TIAs, including ajmalicine, catharanthine, serpentine, and tabersonine, while maintaining wild-type levels of TDC activity. Alkaloid accumulation by highly productive transgenic lines showed considerable instability and was strongly influenced by culture conditions, such as the hormonal composition of the medium and the availability of precursors. High transgene-encoded TDC activity was not only unnecessary for increased productivity, but also detrimental to the normal growth of the cultures. In contrast, high STR activity was tolerated by the cultures and appeared to be necessary, albeit not sufficient, to sustain high rates of alkaloid biosynthesis. We conclude that constitutive over-expression of Str is highly desirable for increased TIA production. However, given its complexity, limited intervention in the TIA pathway will yield positive results only in the presence of a favorable epigenetic environment.

Alkaloids↗
PubMed2005

Systemic aspergillosis with predominant genitourinary manifestations in an immunocompetent man: what we can learn from a disastrous follow-up.

Prostatic aspergillosis is a rare finding with only ten cases reported previously. We report the first case of systemic aspergillosis predominantly presenting with prostatic involvement and, clinically, with urinary retention in an immunocompetent host. Routine transurethral resection was performed due to benign prostatic hyperplasia with subvesical obstruction. Concomitant prostatic aspergillosis was diagnosed without signs of systemic infection. In the clinical follow-up systemic aspergillosis became rapidly progressive requiring complex surgical interventions and long-term antifungal therapy. The current literature is reviewed, and diagnostic and management options are discussed.

Abscess↗
PubMed1992

A novel treatment of global cerebral ischaemia with a glycine partial agonist.

Chronic treatment of gerbils with 1-aminocyclopropanecarboxylic acid (a high affinity, partial agonist at strychnine-insensitive glycine receptors) resulted in a 3-fold increase in survival, a significant improvement in neurological status, and an extensive protection of vulnerable brain regions following severe forebrain ischaemia. A bolus of 1-aminocyclopropanecarboxylic acid 30 min prior to ischaemia did not further improve outcome compared to gerbils receiving their last injection 24 h prior to ischaemia. These findings are consistent with the hypothesis that chronic treatment with a glycine partial agonist desensitizes the N-methyl-D-aspartate receptor complex. Pharmacological intervention at the strychnine-insensitive glycine receptor may be an effective means of ameliorating the consequences of neuronal degeneration caused by excitotoxic phenomena.

Amino Acids↗
PubMed2006

Primer on the practice doctorate for neonatal nurse practitioners.

Recent advances in technology, research, and knowledge have amplified the need for longer and more in-depth education for neonatal nurse practitioners (NNPs). In this article we will briefly review the history of NNP's role and education, define the Doctor of Nursing Practice (DNP), and propose that the practice doctorate is the primary mechanism to meet that need and thus is the future of our profession. Doctor of Nursing Practice programs are designed to prepare the practitioner as an expert clinical NNP. Graduates obtain the highest level of practice expertise integrated with the ability to translate scientific knowledge into complex clinical interventions tailored to meet individual, family, and community health and illness needs. Doctor of Nursing Practice education also expands the scientific basis for practice and clinical practice education, and provides organization and system management and leadership, quality improvement, analytic methods to evaluate practice and apply evidence to practice, enhanced skills in information technology, health policy development, and interdisciplinary collaboration for enhanced patient outcomes.

Directories as Topic↗
PubMed2006

Computerized adaptive testing for follow-up after discharge from inpatient rehabilitation: I. Activity outcomes.

OBJECTIVE: To examine score agreement, precision, validity, efficiency, and responsiveness of a computerized adaptive testing (CAT) version of the Activity Measure for Post-Acute Care (AM-PAC-CAT) in a prospective, 3-month follow-up sample of inpatient rehabilitation patients recently discharged home. DESIGN: Longitudinal, prospective 1-group cohort study of patients followed approximately 2 weeks after hospital discharge and then 3 months after the initial home visit. SETTING: Follow-up visits conducted in patients' home setting. PARTICIPANTS: Ninety-four adults who were recently discharged from inpatient rehabilitation, with diagnoses of neurologic, orthopedic, and medically complex conditions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Summary scores from AM-PAC-CAT, including 3 activity domains of movement and physical, personal care and instrumental, and applied cognition were compared with scores from a traditional fixed-length version of the AM-PAC with 66 items (AM-PAC-66). RESULTS: AM-PAC-CAT scores were in good agreement (intraclass correlation coefficient model 3,1 range, .77-.86) with scores from the AM-PAC-66. On average, the CAT programs required 43% of the time and 33% of the items compared with the AM-PAC-66. Both formats discriminated across functional severity groups. The standardized response mean (SRM) was greater for the movement and physical fixed form than the CAT; the effect size and SRM of the 2 other AM-PAC domains showed similar sensitivity between CAT and fixed formats. Using patients' own report as an anchor-based measure of change, the CAT and fixed length formats were comparable in responsiveness to patient-reported change over a 3-month interval. CONCLUSIONS: Accurate estimates for functional activity group-level changes can be obtained from CAT administrations, with a considerable reduction in administration time.

Activities of Daily Living↗
PubMed2004

Chronic left ventricular failure in the community: Prevalence, prognosis, and predictors of the complete clinical recovery with return of cardiac size and function to normal in patients undergoing optimal therapy.

BACKGROUND: Chronic heart failure (CHF) is a progressive process requiring complex therapeutic interventions. Recently, several trials documented the clinical improvement and regression of left ventricular (LV) remodeling and function in patients on optimized CHF treatment. Furthermore, some authors reported isolated cases of patients who apparently "healed" from CHF. The aim of the present study was to characterize the phenomenon of the normalization in clinical status and LV size and function in CHF patients. METHODS AND RESULTS: We monitored the clinical and echocardiographic parameters of a large cohort of patients with CHF and LV ejection fraction <40% every 6 months for a mean period of 17 +/- 9 months. Twenty of 110 study patients (18%) normalized clinical status and LV size and ejection fraction at any time (mean time 13 +/- 6 months) during the follow up. Such condition, however, was subsequently lost in 11 patients. The normalization was predicted by the nonischemic etiology of CHF, arterial hypertension, absence of diabetes mellitus, carvedilol therapy, and the dose of carvedilol. CONCLUSIONS: The normalization in clinical status and LV size and function is not infrequently observed in patients on optimal CHF therapy. It is predicted by a set of clinical variables and favored by beta-blocker therapy. At medium term, this condition fades in a significant portion of patients.

Adrenergic beta-Antagonists↗
PubMed2004

Fractional flow reserve and complex coronary pathologic conditions.

Fractional flow reserve (FFR) is a well-validated index for assessing the physiologic significance of a coronary stenosis in most clinical conditions encountered in today's catheterisation laboratory. The aim of this paper is to provide a short overview of the theoretical background of the coronary pressure-derived FFR index and its clinical applicability in guiding complex coronary intervention procedures.

Angina, Unstable↗
PubMed2005

The complex business of adapting effective interventions to new populations: an urban to rural transfer.

PURPOSE: To assess the effectiveness of a relatively unaltered version of a sexual risk reduction intervention previously shown to be effective among urban youth, "Original Focus on Kids" (OFOK), compared with a version modified for West Virginia (WVFOK) and a control condition (training in environmental conservation), in altering protective sexual behaviors and perceptions among rural, Appalachian youth. SUBJECTS: Nine hundred ninety-nine youth aged 12 to 16 years from 12 rural counties in West Virginia. METHOD: Randomized, controlled, longitudinal trial of a theory-based prevention intervention. Outcomes were self-reported sexual behaviors and perceptions assessed at baseline, 3, 6, and 9 months postintervention. RESULTS: Both WVFOK and OFOK positively affected perceptions of abstinence but not behaviors. OFOK significantly enhanced some perceptions of condom use compared with both control youth and WVFOK youth, but again, not behaviors. CONCLUSIONS: Overall, neither version was as effective as FOK had been in the original urban setting. The less altered version (OFOK) was more effective, especially with regard to condom-use perceptions, in this new population and cultural setting than the more culturally altered version (WVFOK). In several of the implementation settings, neither version was delivered as intended by the researchers because of logistic issues. Although many of these changes were seemingly minor, such deviations may have significant impact on intervention effect.

Adolescent↗
PubMed1997

The perils of permanent punctal plugs.

PURPOSE: To describe previously unreported complications associated with permanent lacrimal punctal plugs. METHOD: Five oculoplastic practices reviewed patients referred to them over the preceding 2 years for permanent lacrimal punctal plug complications. RESULTS: In 12 patients, 14 lacrimal punctal plugs migrated distally within the lacrimal drainage system, causing symptoms and necessitating surgical removal. CONCLUSION: Luxation of permanent punctal plugs into the distal lacrimal drainage system can occur, sometimes requiring complex surgical intervention.

Foreign-Body Migration↗
PubMed1999

Cardiac reoperations in octogenarians: analysis of outcomes.

BACKGROUND: With the rapid growth of the elderly segment of the population, more octogenarians are referred for complex cardiac interventions, including reoperations. Data regarding the outcomes, quality of life, and long-term results after reoperative open-heart surgical procedures in octogenarians are scarce. METHODS: We retrospectively studied 113 consecutive octogenarians (mean age, 83+/-2.6 years) who underwent reoperative cardiac procedures within a 13-year period. Coronary artery bypass grafting (CABG) was performed in 49 patients (CABG group), valvular procedures (aortic, mitral, or tricuspid valve, alone or in combination) in 35 (valve group), and combined CABG and valve intervention in 29 (combined CABG and valve group). RESULTS: The 30-day mortality rate was 8% (4 of 49) for the CABG group, 9% (3 of 35) for the valve group, and 17% (5 of 29) for the combined CABG and valve group. One- and 5-year actuarial survival rates were, respectively, 85%+/-5% and 58%+/-10% for the CABG group, 78%+/-7% and 53%+/-12% for the valve group, and 69%+/-9% and 63%+/-10% for the combined CABG and valve group. Sixty-one percent of patients in the CABG group, 40% in the valve group, and 38% in the combined CABG and valve group were in New York Heart Association class I or II postoperatively at a mean follow-up time of 2.1+/-2.4 years. Similarly, 91%, 85%, and 80%, respectively, thought that they had an improved quality of life and were satisfied with their functional status. CONCLUSIONS: Cardiac reoperations can be performed successfully in most octogenarians, although with an increased risk, particularly in the combined CABG and valve group. Long-term survival is acceptable with improved quality of life and functional status. However, it is possible that these results could be improved in this high-risk group of patients with earlier referral and surgical intervention, for the effective use of health care resources.

Aged↗
PubMed1999

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation.

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation.

Adaptation, Physiological↗
PubMed1986

Digital subtraction angiography.

Digital subtraction angiography is a new imaging technique that uses a computer to subtract background distractions and to enhance contrast and density. The intravenous administration of contrast material permits safe outpatient screening for arterial disease. The exact role of intravenous digital subtraction angiography in cerebrovascular disease is still in evolution and remains the subject of debate. The value of intravenous digital subtraction angiography in screening for renovascular hypertension is less controversial, but selection of patients remains a subject for further study. Intra-arterial digital subtraction angiography has become a standard imaging technique that offers both the inherent safety produced by reduction of the volume of contrast material and the added safety afforded by reduction of both the size of the catheter and the time required to perform complex arterial interventional procedures. With the evolution of more sophisticated computed technology and radiographic equipment, the impact of both intravenous and arterial digital subtraction angiography will become even more dramatic.

Angiography↗