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New Therapeutic Approaches to Peptic Ulcer Disease: The Role of Helicobacter Pylori.

One of the most common bacterial infections of human involves Helicobacter pylori, a spiral, gram-negative bacterium that is now thought to be a dominant factor in the development of peptic ulcer disease and may be significant in causing certain forms of gastric cancer. Almost 100% of patients with duodenal ulcer and 70 to 90% affected with gastric ulcer are infected with H. pylori. In order to achieve cure of H. pylori--induced ulcer disease, it is necesary to eradicate the bacterial infection. Mere suppression or clearance infection without eradication is associated with a >80% recurrence of the ulcer. The epidemiology, microbiology, and pathogenesis of H. pylori infections are reviewed. Diagnostic methods and optimal treatment strategies for H. pylori infections are examined. The most current diagnostic and treatment algorithms for peptic ulcer disease are discussed critically, and future directions for drug development aimed at eradication of H. pylori infection are considered.

Journal Article↗

Diagnosis and management of renovascular hypertension.

Renovascular hypertension caused by renal artery stenosis accounts for a small portion of overall hypertension but remains important as the most common potentially curable form of high blood pressure. Diagnosis depends on developing an index of suspicion for renovascular hypertension based on the history and physical exam, as well as judicious use of noninvasive and invasive testing. Determining which noninvasive diagnostic test to use remains a persistent dilemma. Treatment options include renal artery angioplasty, arterial stenting, surgery, and medical therapy. The goals of therapy are reduction of blood pressure and protection of renal function. This review discusses the pathophysiology and epidemiology of renovascular hypertension, various noninvasive tests used in diagnosis, and results offered by different treatment modalities. A diagnostic and therapeutic algorithm is offered based on a review of the literature and the experience at our institution.

Algorithms↗

Early identification of individuals with prostate cancer in negative biopsies.

PURPOSE: The use of prostate specific antigen (PSA) to screen individuals for prostate cancer has changed the management of the disease, permitting early detection in men. Repeat biopsies for persistently increased PSA are not uncommon with prostate cancer never being detected in many of the men. The novel prostate cancer marker, EPCA, is expressed throughout the prostate of individuals with prostate cancer but not in those without the disease. MATERIALS AND METHODS: The expression of ECPA was studied to identify those men with initially negative biopsies who were ultimately found to have prostate cancer. Negative biopsies, subsequent biopsies and prostatectomy specimens were evaluated by quantitative immunohistochemistry. RESULTS: The EPCA staining intensity in the samples analyzed from the patient cohort with prostate carcinoma were significantly different compared to controls (p <0.001) with almost no overlap in staining results. Sensitivity of the EPCA immunohistochemistry is 84% and specificity is 85%. CONCLUSIONS: An immunohistochemical test for EPCA could serve as an adjunct to the current diagnostic approach to a patient who undergoes prostate needle biopsy, and could identify individuals with prostate cancer as much as 5 or more years earlier than the current diagnostic approach and algorithms. In addition, this test might also help limit the numbers of biopsies performed as part of subsequent routine evaluation for increased PSA.

Adolescent↗

Chronic prostatitis: Charlottesville to Seattle.

PURPOSE: Since few men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have culturable bacteria by traditional approaches, we used sensitive molecular methods to determine presence of fastidious microorganisms. MATERIALS AND METHODS: We evaluated 135 men with CP/CPPS by standardized clinical evaluation, and by lower tract localization cultures and chamber counts of expressed prostatic secretions of leukocytes. We excluded from study patients with bacteriuria, bacterial prostatitis, urethritis or positive urethral cultures. Prostate biopsy was obtained using a double-needle technique to limit contamination. We chose molecular approaches because previous studies had used culture antigen detection in urine, urethral swabs and expressed prostatic secretions. However, interpretation of such studies is complicated because urogenital samples often acquire bacteria while passing through the urethra. We used specific and broad-spectrum polymerase chain reaction (PCR) assays. RESULTS: Only 10 (8%) of the 135 subjects had positive specific PCR assays, including Mycoplasmia genitalium, Chlamydia trachomatis and Trichomonas vaginalis. Our findings suggested that C. trachomatis, T. vaginalis and M. genitalium may be identified in some patients with CP/CPPS, even among men with no evidence of urethritis and with negative urethral cultures and other assays. The broad-spectrum PCR assays provided the most provocative findings. DNA encoding tetracycline resistance was identified in 25% of subjects, and 77% of subjects had evidence of 16S rDNAs. The white blood cell concentration in the prostatic secretions correlated with identification of 16S rDNAs in prostate tissue (p <0.01). CONCLUSIONS: Delineating the precise role of these organisms in the etiology of CP/CPPS may help define better diagnostic and treatment algorithms.

Chronic Disease↗

Management of portal hypertension.

Complications of portal hypertension are the leading cause of death in patients with liver cirrhosis. Rational medical and endoscopic therapy is guided by a thorough understanding of the underlying pathophysiology of ascites, variceal formation and bleeding, hepatorenal syndrome, and hepatic encephalopathy. The pathophysiology of each clinical entity is reviewed followed by an evidence-based diagnostic and management algorithm.

Acute Disease↗

Perioperative management of intracranial aneurysms and otologic disease.

OBJECTIVE: Diagnosis and treatment of asymptomatic, unruptured intracranial aneurysms (UIA) are areas of longstanding controversy in the neurologic and neurosurgical literature. Treatment decisions require careful consideration of both the potential for aneurysm rupture as well as the risks associated with repair. Studies examining the natural history of UIA, the morbidity and mortality associated with subarachnoid hemorrhage (SAH), and the various treatment options have led to general guidelines for UIA management. In the literature, the simultaneous presence of otologic disease and UIA has not been introduced or addressed. It is unknown whether surgical treatment of middle ear disease has an effect on the natural history of UIA. STUDY DESIGN: Two illustrative patients with UIA discovered incidentally on radiographic evaluation of middle ear disease are presented. METHODS: Patients were managed according to diagnostic and treatment strategies developed and validated in the neurosurgical literature. RESULTS: Both patients underwent uneventful endovascular embolization of their intracranial aneurysms before middle ear surgery. The intra- and postoperative courses were uncomplicated without symptoms related to either their history of intracranial aneurysms or the prior embolization. CONCLUSIONS: Application of neurosurgical diagnostic and treatment algorithms to otology patients in the perioperative setting is appropriate. Established risk factors such as the size and location of the intracranial aneurysm, prior SAH, and patient age should guide treatment planning in all cases of UIA. Additional research is needed to evaluate the influence of otologic procedures on the natural history of UIA. In addition, studies are needed to evaluate the role of preoperative screening for UIA in otologic surgery candidates.

Adult↗

Inflammatory pathways and immune dysregulation in pediatric postoperative septic shock: A study integrating transcriptomics, machine learning and molecular docking.

This study elucidates the molecular and immune regulatory mechanisms of pediatric postoperative septic shock. Transcriptomic data were obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using the limma package, and gene co-expression modules were constructed using Weighted Gene Co-expression Network Analysis. Functional enrichment was performed via gene set enrichment analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Immune cell infiltration was assessed using ESTIMATE and CIBERSORT. Mendelian randomization was applied to explore causal relationships between gene expression and septic shock. Feature genes were selected using machine learning algorithms, and a diagnostic nomogram model was constructed. Finally, molecular docking analysis was performed to screen and evaluate the binding affinity of traditional Chinese medicine monomers to core target proteins. A total of 1331 differentially expressed genes were identified, and the turquoise module was strongly correlated with septic shock. Enrichment analysis revealed significant activation of IL-6/JAK/STAT3, TNF-&#x3b1;/NF-&#x3ba;B, and PI3K/Akt/mTOR pathways. Immune infiltration analysis indicated suppressed immune scores and imbalances in neutrophils, macrophages, T cells, and B cells. Mendelian randomization confirmed causal associations for 6 genes, including PIM3. The predictive model based on feature genes demonstrated high diagnostic performance. Molecular docking suggested that quercetin and astramembrannin I could stably bind PIM3. This study systematically identified core genes, dysregulated immune pathways, and candidate small-molecule interventions in pediatric septic shock, providing novel insights for early diagnosis and targeted therapy.

Humans↗

Review article: exploration of the genetic aetiology of inflammatory bowel disease--implications for diagnosis and therapy.

Genomic technologies offer new approaches to the investigation of the aetiology and pathophysiology of inflammatory bowel disease. An important field relevant to inflammatory bowel disease therapy is the pharmacogenetic investigation of gene variations that may predict responses to certain medications in order to target these therapeutic interventions more precisely. To date, only about 12,000 of the estimated 30,000-50,000 human genes have been characterized. Therefore, the use of techniques for a global analysis of gene expression may allow the identification of new pathways or molecules in the therapeutic mechanisms of drugs. Recently, NOD2 has been identified as the first disease gene in inflammatory bowel disease. DLGS and OCTN-1 have been named as further disease genes. Although the detection of disease-associated variants has greatly advanced our understanding of the primary events that lead to the development of inflammatory bowel disease in a subgroup of patients with Crohn's disease, the implications of the findings for diagnostic and therapeutic algorithms are less clear. However, it appears that there is a clear association between certain subphenotypes of Crohn's disease and the disease-associated variants in the NOD2 gene. It can be anticipated that genomic findings will profoundly influence the future therapy of inflammatory bowel disease.

Gastrointestinal Agents↗

Assessment of blunt abdominal trauma.

Computerized tomography (CT) scanning and diagnostic peritoneal lavage have often been seen as competing modalities in the assessment of blunt abdominal trauma. Each has its own strengths and weakness. A judicious use of both modalities can result in improved diagnostic accuracy. An algorithm for their appropriate use is suggested.

Abdominal Injuries↗

Effective observation unit treatment of decompensated heart failure.

There is little information on the effectiveness of emergency department (ED) observation unit (OU) heart failure (HF) therapy. The authors' objective was to evaluate outcomes after implementation of an ED-OU treatment protocol for HF exacerbation. Unblinded assessment of the effectiveness of an HF protocol was performed, controlled by outcome for 9 months prior to implementation. This included diagnostic and therapeutic algorithms, cardiology consultation, close monitoring, patient education, and discharge planning. Adverse outcomes were defined as the 90-day rates of ED HF revisits, hospital HF readmissions, or death, as determined by chart review, computer database search, and phone follow-up. One hundred fifty-four patients were enrolled; 50 entered before, and 104 after protocol implementation. Only six (12%) in the preprotocol and one (1%) of the postprotocol group were lost to follow-up. After an OU visit, postprotocol 90-day ED HF revisit rates declined 56% (0.90-0.51; p<0.0000) and the 90-day HF rehospitalization rate decreased 64% (0.77-0.50; p=0.007). The 90-day rates of death and OU HF readmission decreased from 4% to 1% (p=0.096) and 18% to 11% (p=0.099), respectively. An intensive outpatient ED OU HF management protocol safely decreases 90-day rates of emergency department visits and inpatient hospitalizations.

Adult↗

Prevalence of supraventricular arrhythmias from the automated analysis of data stored in the DDD pacemakers of 617 patients: the AIDA study. The AIDA Multicenter Study Group. Automatic Interpretation for Diagnosis Assistance.

The confirmation of the occurrence of supraventricular arrhythmias (SVAs) is possible only if a surface electrocardiogram (ECG) is recorded during an episode, or if SVAs occur during 24 h ambulatory monitoring (Holter). The automatic interpretation of memory functions in DDD pacemakers may be useful in this diagnostic task over longer periods of follow up. This hypothesis was tested in 384 men and 233 women (mean age = 70 +/- 11 years) who had received Chorus 6034/6035, 6234 or 7034 pacemakers (ELA Medical, Montrouge, France) with fall-back function in case of sustained SVAs. The Automatic Interpretation for Diagnostic Assistance (AIDA) algorithm included in these pacemakers was compared with 24 h Holters recorded simultaneously (D1) and with the clinical history of symptoms consistent with SVAs up to 28 days of follow up (D28). Indications for pacing were atrioventricular block (AVB) in 269 patients, sinus node dysfunction (SND) in 248, and AVB + SND in 100. SVAs were documented before implant in 199 patients (32%). Among the 617 patients included at D1, 76 (12.4%) developed at least one SVA episode, lasting between 1 min and 24 hours, simultaneously recorded on Holter and by AIDA with a 93.8% sensitivity and 94.2% specificity. Data from 354 patients were available for analysis at D28. AIDA diagnosed SVAs in 179 patients (50.6%), 104 of whom (65%) had remained asymptomatic and 117 of whom (65%) had had no SVA documented before implant. Among the 354 patients, AIDA diagnosed SVAs in 76 (21%) asymptomatic patients who had no known SVA before implant. The prevalence of SVA in our AVB population was higher than reported in previous studies: 89 patients (56.3%) with AVB had SVAs versus 90 patients (45.9%) with other diagnoses (p = 0.55). Furthermore atrial pacing was associated with fewer SVAs. These first clinical results of the AIDA study demonstrate that the memory functions of Chorus pacemakers and the AIDA software are reliable to analyze the prevalence of SVA at 1 month of follow-up. From a clinical point of view, AIDA is a valuable tool to evaluate the efficacy of antiarrhythmic therapy, particularly as it pertains to the prevention of stroke due to atrial fibrillation.

Aged↗

Reengineering the emergency evaluation of chest pain.

This article presents strategies for enhancing the emergency department care delivered to patients with chest pain and suspected acute myocardial infarction. It also describes the planning and implementation of an emergency department reengineering project at a university medical center. The establishment of chest pain evaluation centers within emergency departments has been associated with improved clinical outcomes and cost control. Creating such a center requires careful revamping of diagnostic and treatment algorithms, a process that must be based on information from all departments affected by the changes.

Baltimore↗

Spondylolysis: a critical review.

AIM: To provide an understanding of the current concepts in the natural history, pathophysiology, diagnosis, and treatment of spondylolysis based on the available medical literature. METHODS: Articles were selected for review by the following methods: (a) MEDLINE searches with review of abstracts to select relevant articles; (b) review of multiple textbooks considered likely to contain information on spondylolysis; (c) review of references in articles identified by (a) and (b). Over 125 articles were ultimately reviewed fully. Publications were selected for inclusion in this article on the basis of perceived scientific and historical merit, particularly as thought to be relevant to achieving the stated purpose of this review. As no controlled clinical trials were identified, this could not be used as an inclusion criterion. CONCLUSIONS: Isthmic spondylolysis is considered to represent a fatigue fracture of the pars interarticularis of the neural arch. There is a relatively high incidence of radiographically identified spondylolysis in the general population, but the vast majority of these lesions probably occur without associated symptoms. Symptomatic pars lesions appear to be particularly a clinical problem in adolescents, especially adolescent athletes. The optimal diagnostic and treatment algorithms are not well identified in the current literature. Multiple imaging studies may have a role in the diagnosis of a pars lesion, and treatment seems likely to require at least relative rest and physical rehabilitation with consideration of bracing or, rarely, surgical intervention depending on the clinical context.

Humans↗

A survey of decision aids for clinicians.

Inconsistency in applying medical knowledge is a major reason for varying standards of medical care. Five types of aid have been introduced into medicine to help decision-making: questionnaires, algorithms, database systems, diagnostic systems, and, finally, computer-based decision-support systems. Of these, the most effective act as reminder or prompt systems to assist doctors without threatening their clinical freedom.

Bayes Theorem↗

Use of symptoms and signs to diagnose maxillary sinusitis in general practice: comparison with ultrasonography.

OBJECTIVE: To establish the incidence of maxillary sinusitis in general practice and the predictive value of symptoms and signs. DESIGN: Population based study. SETTING: 9 general practices with 15,220 patients aged 15 years and older on the list. PATIENTS: 400 patients with 441 episodes in whom practitioners intended to confirm or to exclude sinusitis. MAIN OUTCOME MEASURES: Results of ultrasonography and signs and symptoms associated with positive results. RESULTS: 212 of the 441 episodes were confirmed by ultrasonography. 15.7 episodes occurred per 1000 adults per year. The five symptoms beginning with common cold (beta coefficient = 1.035), purulent rhinorrhoea (0.996), pain at bending (0.950), unilateral maxillary pain (0.640), and pain in teeth (0.606) were associated with positive results on ultrasonography. General practitioners' clinical diagnoses were correct in 177 episodes, false positive in 88, false negative in 22, and uncertain in 154. With an algorithm using the five weighted symptoms 243 of the diagnoses would have been correct, but 110 would remain uncertain and 44 cases would have been missed. CONCLUSION: The five symptoms algorithm would improve diagnostic accuracy of general practitioners, but incorrect and uncertain diagnoses cannot be avoided.

Adolescent↗

Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative.

OBJECTIVE: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study's generalisability. METHODS: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. RESULTS: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both. CONCLUSIONS: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.

Algorithms↗

Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes: cluster randomised controlled trial.

OBJECTIVE: To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes. DESIGN: Cluster randomised controlled trial. SETTING: 24 nursing homes in Ontario, Canada, and Idaho, United States. PARTICIPANTS: 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care. Outcomes were measured in 4217 residents. INTERVENTIONS: Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach--small group interactive sessions for nurses, videotapes, written material, outreach visits, and one on one interviews with physicians. MAIN OUTCOME MEASURES: Number of antimicrobials prescribed for suspected urinary tract infections, total use of antimicrobials, admissions to hospital, and deaths. RESULTS: Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference -0.49, 95% confidence intervals -0.93 to -0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference -9.6%, -16.9% to -2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighted mean difference -0.37, -1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms. CONCLUSION: A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes.

Aged↗

Evaluation of real time polymerase chain reaction assays for confirmation of Neisseria gonorrhoeae in clinical samples tested positive in the Roche Cobas Amplicor assay.

OBJECTIVE: Development of a rapid, sensitive, and accurate assay for confirmation of Neisseria gonorrhoeae in clinical samples. METHOD: Two real time polymerase chain reaction (PCR) assays, developed on the LightCycler for amplification of the N gonorrhoeae cppB gene, were utilised for confirmation of this bacterial pathogen in samples positive by the Roche Cobas Amplicor assay. Performance characteristics of the two assays were compared with other commercial nucleic acid amplification assays, including the Abbott LCx and Roche 16S rRNA tests. RESULTS: All related Neisseria as well as other bacterial species tested negative by both cppB gene based assays, whereas 120 N gonorrhoeae clinical isolates from various geographical regions gave in positive results. Both assays had a sensitivity of one copy per reaction. 122 clinical samples positive and another 50 samples negative for N gonorrhoeae by Roche Cobas Amplicor were selected from a specimen pool of more than 3000 women tested previously. Overall, 73 of 122 (59.8%) samples were confirmed as positive. The two real time assays had sensitivities of 99% and 100% and specificities of 98% and 100%, respectively. The 16S and LCx assays produced similar results to the real time assays, indicating a similar sensitivity to and specificity of both real time assays. CONCLUSION: The data from this study highlight the need to confirm N gonorrhoeae positive Cobas Amplicor PCR results as an important part of the testing algorithm of all diagnostic laboratories utilising this assay.

DNA, Bacterial↗