Pregnancy and phaeochromocytoma/paraganglioma: clinical clues affecting diagnosis and outcome - a systematic review.

BACKGROUND: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. OBJECTIVE: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. SEARCH STRATEGY: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. SELECTION CRITERIA: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis. MAIN RESULTS: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis. CONCLUSION: Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome. TWEETABLE ABSTRACT: Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.

Intravitreal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: an optical coherence tomography study.

AIM: To investigate the use of intravitreal triamcinolone acetonide (IVTA) for the treatment of diabetic macular oedema (DMO) unresponsive to previous laser photocoagulation. METHOD: A retrospective, interventional, non-comparative case series. There were 30 eyes of 22 consecutive patients with refractory DMO. An intravitreal injection of triamcinolone acetonide at the dose of 4 mg in 0.1 ml was administered. Best corrected visual acuity was measured at each examination. In addition the central macular thickness was quantitatively measured by optical coherence tomography (OCT) examination at each visit. The amount of hard exudates deposition in the macula was subjectively evaluated using colour fundus photographs. RESULTS: 30 eyes of 22 patients completed 6 months or more of follow up and were included in the study. Mean (SD) visual acuity improved from 0.17 (0.12) at baseline to 0.34 (0.18), 0.36 (0.16), and 0.31 (0.17) at the 1, 3, and 6 month follow up respectively. Mean (SD) OCT macular thickness decreased from 476 (98.32) microm at baseline to 277.46 (96.77) microm, 255.33 (95.73) microm, and 331.25 (146.76) microm at the 1, 3, and 6 month follow up period respectively. 18 and seven eyes completed 12 months and 18 months of follow up, respectively. Mean (SD) visual acuity was 0.36 (0.15) and 0.35 (0.16) at the 12 and 18 month follow up period respectively. 12 eyes received two, seven eyes received three, and two eyes received four IVTA injections. The mean (SD) interval between the first and second IVTA injection was 5.7 (2.67) months and between the second and third was 5.7 (3.25) months. Hard exudates were present in the macula at baseline in all eyes. Progressive reduction in the number and size of the hard exudates was noted after IVTA in all cases. Intraocular pressure was raised above 21 mm Hg in 12 (40%) of 30 eyes. Two eyes developed posterior subcapsular cataract and two developed vitreous haemorrhage. CONCLUSIONS: IVTA is a promising treatment for patients with DMO refractory to laser treatment. IVTA is effective in improving vision, reducing macular thickness, and inducing reabsorption of hard exudates. Further investigation is warranted to assess the safety of IVTA for the treatment of DMO.

A critical pathway for electronic medical record selection.

Electronic medical records (EMRs) are increasingly becoming a necessary tool in health care. Given their potential to influence every aspect of health care, there has been surprisingly little rigorous research applied to this important piece of emerging health technology. An initial phase of the COMPETE study, which is examining the impact of EMRs on efficiency, quality of care and privacy concerns, involved a rigorous "critical pathway" approach to EMR selection for the study. A multidisciplinary team with clinical, technical and research expertise led an 8-stage evaluation process with direct input from user physicians at each stage. An iterative sequence of review of EMR specifications and features, live product demonstrations, site visits, and negotiations with vendors led to a progressive narrowing of the field of eligible EMR systems. Final scoring was based on 3 main themes of clinical usability, data quality and support/vendor issues. We believe that a rigorous, multidisciplinary process such as this is required to maximize success of any EMR implementation project.

A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby's fundus dystrophy.

Sorsby's fundus dystrophy (SFD) is a dominantly inherited degenerative disease of the retina that leads to loss of vision in middle age. It has been shown to be caused by mutations in the gene for tissue inhibitor of metalloproteinases-3 (TIMP-3). Five different mutations have previously been identified, all introducing an extra cysteine residue into exon 5 (which forms part of the C-terminal domain) of the TIMP-3 molecule; however, the significance of these mutations to the disease phenotype was unknown. In this report, we describe the expression of several of these mutated genes, together with a previously unreported novel TIMP-3 mutation from a family with SFD that results in truncation of most of the C-terminal domain of the molecule. Despite these differences, all of these molecules are expressed and exhibit characteristics of the normal protein, including inhibition of metalloproteinases and binding to the extracellular matrix. However, unlike wild-type TIMP-3, they all form dimers. These observations, together with the recent finding that expression of TIMP-3 is increased, rather than decreased, in eyes from patients with SFD, provides compelling evidence that dimerized TIMP-3 plays an active role in the disease process by accumulating in the eye. Increased expression of TIMP-3 is also observed in other degenerative retinal diseases, including the more severe forms of age-related macular degeneration, the most common cause of blindness in the elderly in developed countries. We hypothesize that overexpression of TIMP-3 may prove to be a critical step in the progression of a variety of degenerative retinopathies.

Localization of the functional domains of human tissue inhibitor of metalloproteinases-3 and the effects of a Sorsby's fundus dystrophy mutation.

A transient COS-7 cell expression system was used to investigate the functional domain arrangement of tissue inhibitor of metalloproteinases-3 (TIMP-3), specifically to assess the contribution of the amino- and carboxyl-terminal domains of the molecule to its matrix metalloproteinase (MMP) inhibitory and extracellular matrix (ECM) binding properties. Wild type TIMP-3 was entirely localized to the ECM in both its glycosylated (27 kDa) and unglycosylated (24 kDa) forms. A COOH-terminally truncated TIMP-3 molecule was found to be a non-ECM bound MMP inhibitor, whereas a chimeric TIMP molecule, consisting of the NH2-terminal domain of TIMP-2 fused to the COOH-terminal domain of TIMP-3, displayed ECM binding, albeit with a lower affinity than the wild type TIMP-3 molecule. Thus the functional domain arrangement of TIMP-3 is analogous to that seen in TIMP-1 and -2, namely that the NH2-terminal domain is responsible for MMP inhibition whereas the COOH-terminal domain is most important in mediating the specific functions of the molecule. A mutant TIMP-3 in which serine 181 was changed to a cysteine, found in Sorsby's fundus dystrophy, a hereditary macular degenerative disease, was also expressed in COS-7 cells. This gave rise to an additional 48-kDa species (possibly a TIMP-3 dimer) that retained its ability to inhibit MMPs and localize to the ECM. These data favor the hypothesis that the TIMP-3 mutations seen in Sorsby's fundus dystrophy contribute to disease progression by accumulation of mutant protein rather than by the loss of functional TIMP-3.

A Clinical Informatics Network (CLINT) to support the practice of evidence-based health care.

CLINT, which stands for Clinical Informatics NeTwork, is one of the clinical informatics initiatives in development at McMaster University's Health Information Research Unit. CLINT is a microcomputer-based system of over 60 workstations providing 24 hour availability of a set of clinical information resources to clinicians throughout our teaching hospital. CLINT encompasses three domains: (1) a user adaptable clinician-computer interface, (2) unique evidence-based health care content, and (3) automated data collection and viewing tools. An objective of the CLINT project is to determine CLINT's impact on the practice of health care. Early analysis of our data has revealed that over the past year, there has been widespread use of CLINT by clinicians from all clinical domains. Our next task is to evaluate CLINT's usefulness.

CLINT: a clinical informatics system for an internal medicine ward.

This paper describes a clinical informatics system that provides access to electronic information management tools for clinicians. The Clinical Informatics Network (CLINT) provides a variety of tools for accessing information on an internal medicine ward. Evaluations based on the use of the tools will provide insight to clinicians' information needs, and how these needs can be addressed using electronic information management tools. Better access to information could enhance the quality of patient care.

GAP: a computer-assisted design tool for the development and analysis of evidence-based automated questionnaires.

This paper describes the design and use of a computer-assisted design tool for developing evidence-based automated questionnaires that may assist health practitioners to implement clinical practice guidelines. The Guideline Application Program (GAP) facilitates the design, development, testing, customization, and implementation of interactive patient-computer questionnaires, the analysis of patient-derived information, and the clinical application of practice guidelines that require knowledge of multiple patient-specific characteristics. GAP is being used to create a variety of software applications for HealthQuiz and Microsoft Windows-compatible computers. GAP-generated applications are presently used to support preventive care guideline implementation in primary care settings, preoperative screening in anesthesia clinics, student health screening in Universities, hormone replacement counseling for peri-menopausal women, and patient-reported data collection in various clinical research projects.

Effects of computer-based clinical decision support systems on clinician performance and patient outcome. A critical appraisal of research.

OBJECTIVE: To review the evidence from controlled trials of the effects of computer-based clinical decision support systems (CDSSs) on clinician performance and patient outcomes. DATA SOURCES: The literature in the MEDLARS, EMBASE, SCISEARCH, and INSPEC databases was searched from 1974 to the present. Conference proceedings and reference lists of relevant articles were reviewed. Evaluators of CDSSs were asked to identify additional studies. STUDY SELECTION: 793 citations were examined, and 28 controlled trials that met predefined criteria were reviewed in detail. DATA EXTRACTION: Study quality was assessed, and data on setting, clinicians and patients, method of allocation, computer system, and outcomes were abstracted and verified using a structured form. Separate summaries were prepared for physician and patient outcomes. Within each of these categories, studies were classified further according to the primary purpose of the CDSS: drug dose determination, diagnosis, or quality assurance. RESULTS: Three of 4 studies of computer-assisted dosing, 1 of 5 studies of computer-aided diagnosis, 4 of 6 studies of preventive care reminder systems, and 7 of 9 studies of computer-aided quality assurance for active medical care that assessed clinician performance showed improvements in clinician performance using a CDSS. Three of 10 studies that assessed patient outcomes reported significant improvements. CONCLUSIONS: Strong evidence suggests that some CDSSs can improve physician performance. Additional well-designed studies are needed to assess their effects and cost-effectiveness, especially on patient outcomes.

A critical appraisal of the literature on the effects of computer-based clinical decision support systems on clinician performance and patient outcomes.

OBJECTIVE: To review the evaluations of computer-based clinical decision support systems (CDSS's). DATA SOURCES: The literature collected in the MEDLARS, EMBASE, SCISEARCH and INSPEC databases was searched from 1974 to the present. The reference lists of relevant articles were reviewed as were conference proceedings. STUDY SELECTION: Prospective, controlled studies were included. Studies were rated for methodological quality. DATA EXTRACTION: Study quality was assessed and data on study setting, subjects, method of allocation, and computer system were collected and verified using a structured form. CONCLUSIONS: There is considerable heterogeneity in both systems evaluated and design features of those systems. Future evaluations of CDSS's should focus on methodological issues in order to enhance overall quality of evaluations.

PREOP: development of an evidence-based expert system to assist with preoperative assessments.

PREOP is a prototype expert system that is designed to provide physicians with evidence-based recommendations concerning the assessment and care of patients with comorbid medical problems who are about to undergo surgery. The knowledgebase for this system is currently undergoing transition from the conventional advice of medical experts, which is variably related to evidence published in the medical literature, to a more formal approach in which the best available evidence is used for each recommendation and the quality of the evidence made apparent to the user. This work seeks to address important questions concerning improvement of the information contained in expert knowledgebases, namely, how to find and recognize new evidence when it is published, how to assess the quality of evidence in a uniform and efficient fashion, how to replace evidence in the knowledgebase efficiently when it has been superseded by higher quality evidence, and how to represent evidence in a manner that is most valuable for the user.