Midodrine for the weaning of vasopressor infusions.

WHAT IS KNOWN AND OBJECTIVE: Midodrine, an orally available α1-agonist indicated for the treatment of orthostatic hypotension, has been used at our institution as an adjunctive treatment to provide haemodynamic support to facilitate intravenous (IV) vasopressor weaning. Limited published data exist for this off-label use; thus, the objective of this study was to evaluate outcomes in patients who received midodrine for IV vasopressor weaning compared to control patients. METHODS: This retrospective comparison included adult ICU patients admitted to our institution from January 2007 to March 2012. The primary outcome was the time to IV vasopressor discontinuation after midodrine initiation. Secondary outcomes included a comparison between midodrine and control patients of the time from IV vasopressor discontinuation to ICU discharge, hospital and ICU length of stay (LOS), and the number of ICU readmissions. RESULTS AND DISCUSSION: The analysis included 188 patients (94 midodrine and 94 control). Patients discontinued IV vasopressors a median of 1·2 days (IQR 0·5-2·8) after midodrine initiation. ICU discharge occurred sooner after IV vasopressor discontinuation (0·8 vs. 1·5 days, P = 0·01), and 96% of patients remained off IV vasopressors after midodrine treatment. Hospital LOS was longer in midodrine patients (P < 0·01), but there were no differences in ICU LOS or readmissions. Adverse event rates after midodrine use were consistent with those observed in other studies. WHAT IS NEW AND CONCLUSION: Midodrine may serve as a useful adjunct to wean IV vasopressors in difficult-to-wean patients. Further studies are needed to assess the efficacy and safety of midodrine for this indication.

A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR).

INTRODUCTION AND HYPOTHESIS: The objective of this study was to create a valid, reliable, and responsive sexual function measure in women with pelvic floor disorders (PFDs) for both sexually active (SA) and inactive (NSA) women. METHODS: Expert review identified concept gaps and generated items evaluated with cognitive interviews. Women underwent Pelvic Organ Prolapse Quantification (POPQ) exams and completed the Incontinence Severity Index (ISI), a prolapse question from the Epidemiology of Prolapse and Incontinence Questionnaire (ISI scores), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Female Sexual Function Index (FSFI). Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping. Cronbach's alpha measured internal consistency. Factor correlations evaluated criterion validation. Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery. RESULTS: A total of 589 women gave baseline data, 200 returned surveys after treatment, and 147 provided test-retest data. For SA women, 3 subscales each in 2 domains (21 items) and for NSA women 2 subscales in each of 2 domains (12 items) emerged with robust psychometric properties. Cronbach's alpha ranged from .63 to .91. For SA women, correlations were in the anticipated direction with PFDI-20, ISI, and FSFI scores, POPQ, and EPIQ question #35 (all p < .05). PFDI-20, ISI, and FSFI subscale change scores correlated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire International Urogynecological Association-revised (PISQ-IR) factor change scores and with mean change scores in women who underwent surgery (all p < .05). For NSA women, PISQ-IR scores correlated with PFDI-20, ISI scores, and with EPIQ question #35 (all p < .05). No items demonstrated differences between test and retest (all p ≥ .05), indicating stability over time. CONCLUSIONS: The PISQ-IR is a valid, reliable, and responsive measure of sexual function.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Evidence-based Dentistry: Part VI. Critical Appraisal of the Dental Literature: Papers About Diagnosis, Etiology and Prognosis.

Critical appraisal methods assist the reader in assessing the validity (closeness to the truth) and the relevance (usefulness in everyday practice) of research findings. The specific techniques of critical appraisal can vary somewhat, depending on the nature of the research question. In this paper, the final in a 6-part series on evidence-based dentistry, frameworks are presented to enable the judicious reader of the dental literature to apply sensible questions to the evaluation of papers related to diagnosis, etiology and prognosis.

Rod contributions to the electroretinogram of the dark-adapted developing zebrafish.

Anatomical studies of the developing zebrafish retina have shown that rods approach maturity at about 15 days postfertilization (dpf). Past work has examined the photopic spectral sensitivity function of the developing zebrafish, but not spectral sensitivity under dark-adapted conditions. This study examined rod contributions to the dark-adapted spectral sensitivity function of the ERG b-wave component in developing zebrafish. ERG responses to stimuli of various wavelengths and irradiances were obtained from dark-adapted fish at 6-8, 13-15, 21-24, and 27-29 dpf. The results show that dark-adapted spectral sensitivity varied with age. Spectral sensitivity functions of the 6-8 and 13-15 dpf groups appeared to be cone dominated and contained little or no rod contributions. Spectral sensitivity functions of the 21-24 and 27-29 dpf groups appeared to have both rod and cone contributions. Even at the oldest age group tested, the dark-adapted spectral sensitivity function did not match the adult function. Thus, consistent with anatomical findings, the rod contributions to the ERG spectral sensitivity function appear to develop with age; however, these contributions are still not adult-like by 29 dpf, which is contrary to anatomical work. These results illustrate that the zebrafish is an excellent model for visual development.

Evidence-based dentistry: Part V. Critical appraisal of the dental literature: papers about therapy.

Evidence-based dentistry involves defining a question focused on a patient-related problem and searching for reliable evidence to provide an answer. Once potential evidence has been found, it is necessary to determine whether the information is credible and whether it is useful in your practice by using the techniques of critical appraisal. In this paper, the fifth in a 6-part series on evidence-based dentistry, a framework is described which provides a series of questions to help the reader assess both the validity and applicability of an article related to questions of therapy or prevention.

Clinical practice guidelines in dentistry: Part II. By dentists, for dentists.

There is a growing interest in clinical practice guidelines (CPGs) for all health care providers. As discussed in the first paper of this 2-part series, there are many misperceptions about guidelines and their potential risks and benefits. The dental profession in Canada, cognizant of both the importance and the challenges of developing sound, credible and relevant guidelines for dentists, has created a unique, autonomous collaboration of multiple stakeholders, the Canadian Collaboration on CPGs in Dentistry (CCCD). This paper discusses the history, structure and processes of the CCCD and introduces the first guideline under development by and for Canadian dentists.

Evidence-based dentistry: Part III. Searching for answers to clinical questions: finding evidence on the Internet.

The Internet is rapidly becoming a valuable source of information for all health care professionals, as well as for the consumers of health care--patients and their families and friends. Information on the Internet is uncontrolled and generally unevaluated. The quality filter of peer review, present in published dental journals, is usually lacking in Internet-based health sources. There are, however, a number of well-developed, highly-credible and useful resources available online that provide evidence-based information. In this paper, the third in a 6-part series on evidence-based practice, we discuss some of the sites that we have found to be most helpful for learning, teaching and practising evidence-based care.

Evidence-based dentistry: Part IV. Research design and levels of evidence.

Previous papers in this series on evidence-based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically searching for evidence. The next step, critical appraisal of the evidence, is made easier if one understands the basic concepts of clinical research design. The strongest design, especially for questions related to therapeutic or preventive interventions, is the randomized, controlled trial. Questions relating to diagnosis, prognosis and causation are often studied with observational, rather than experimental, research designs. The strongest study design should be used whenever possible. Rules have been established to grade research evidence. This paper, the fourth in the series, presents an overview of research methodology most commonly used in the dental literature.

Clinical practice guidelines in dentistry: Part I. Navigating new waters.

Clinical Practice Guidelines (CPGs) are tools, developed by and for practitioners, to assist in clinical decision making. They are designed to enhance, not replace, clinical judgement and expertise. Well-developed guidelines use the evidence-based approach. The research evidence related to a topic is assembled in a systematic, comprehensive and unbiased manner. Recommendations are made based on the evidence and practitioner feedback is sought prior to formulating the final practice guideline. There are many misperceptions about CPGs and some dentists are wary about their development and use. In this paper, we explore some of the reasons for these misperceptions, review the benefits of sound guidelines, and discuss some of the challenges for guideline development in dentistry in Canada

Evidence-based dentistry: Part II. Searching for answers to clinical questions: how to use MEDLINE.

The ability to conduct efficient literature searches is fundamental to the practice of evidence-based dentistry. In the second part of this series on evidence-based dentistry, strategic literature search techniques are discussed. MEDLINE, because of its breadth, depth and continuous maintenance by the U.S. National Library of Medicine (NLM), is the best source of evidence for health care. Although there are many gateways to MEDLINE, this paper highlights the user-friendly versions of MEDLINE offered free on the Internet by the NLM. The use of well-established search tactics and the unique features of the NLM sites facilitate rapid, effective literature searches.

Evidence-based dentistry: Part I. Getting started.

This article is the first in a 6-part series on the methods of evidence-based dentistry. To practise in an evidence-based manner, practitioners must be able to formulate a clear question, find the best available evidence efficiently, evaluate the evidence systematically and, if it is relevant and credible, apply the results of the appraisal to their practice. In this paper, we will look at the process of building a clinical question using key elements. Examples of questions most commonly encountered in everyday dental practice are provided.

Adverse outcomes in a controlled trial of pergolide for cocaine dependence.

We conducted a double-blind, multiple dose comparison study of pergolide versus placebo for the treatment of cocaine dependence. In the present study, we examined patients who met criteria for cocaine dependence without comorbid alcohol dependence (N = 255). Study completion rates favored placebo (48.9%) over the low dose (33.3%) and high dose (21.5%) pergolide subjects (chi2(2) = 14.17, p < or = 0.001). Treatment effectiveness scores (TES) were significantly higher for the placebo group (31.7) than the low dose (25.2) and high dose (14.2) pergolide groups (F2,252 = 6.21, p = 0.002). There were no significant differences in side effect profiles after first dose of pergolide or placebo, or at study termination. Results of this study suggest that pergolide was not efficacious in the treatment of cocaine dependence due to reduced study participation. Caution regarding the outpatient use of pergolide in similar populations is warranted.

Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and meta-analysis of randomized controlled trials.

PURPOSE: To identify, classify, and evaluate agents used in the prophylaxis of oral mucositis in irradiated head and neck cancer patients. METHODS: Data sources included multiple databases and manual citation review of relevant literature. Based on the eligibility criteria, 59 studies were independently reviewed by two reviewers. Forty-two studies were included in the classification scheme, of which 15 met the criteria for inclusion in the meta-analysis. Data were extracted by duplicate independent review, with disagreement resolved by consensus. RESULTS: Overall, the interventions reduced the odds of developing severe oral mucositis, when assessed by clinicians, by 36% (OR: 0.64; 95% CI: 0.46, 0.88). Subgroup analysis suggested that only the narrow-spectrum antibacterial lozenges were effective (OR: 0.45; 95% CI: 0.23, 0.86); however, the power of the aggregated data in the other classes may have been insufficient to detect differences. When the outcome was assessed by patients, no significant difference was seen in the outcome between the treatment and the control groups (OR: 0.79; 95% CI: 0.56-1.12). CONCLUSIONS: Overall, interventions chosen on a sound biologic basis to prevent severe oral mucositis are effective. In particular, when oral mucositis is assessed by clinicians, narrow-spectrum antibiotic lozenges appear to be beneficial. Methodologic limitations were evident in many of the studies. Further research using validated measurement tools in larger, methodologically sound trials is warranted.

The building blocks of evidence-based dentistry.

The practice of dentistry is becoming more complex and challenging. Changing socio-demographic patterns, patients as knowledgeable health care consumers, rapid technical advances and the information "explosion" all place greater demands on clinical decision making. The need for reliable information and the electronic revolution have come together to allow the "paradigm shift" towards evidence-based health care to progress swiftly. Evidence-based dentistry closes the gap between clinical research and real world dental practice and provides dentists with powerful tools to interpret and apply research findings. Central to evidence-based practice is the systematic literature review, which synthesizes the best evidence and provides the basis for clinical practice guidelines.

Solvent oriented hobbies and the risk of systemic sclerosis.

OBJECTIVE: To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody. METHODS: Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70. RESULTS: Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). CONCLUSION: While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

Port-access coronary artery bypass grafting: technique and comparative results.

BACKGROUND: Interest in minimally invasive coronary artery bypass grafting (CABG) continues to grow, and the techniques evolve. Our study examines the technical strategies of port-access (PA) CABG and compares results between PA CABG and conventional CABG. METHODS: Two hundred and twenty-nine consecutive patients underwent PA CABG from December 1996 through July 1998. Postoperative complications were compared with a matched cohort of conventional access patients. Operative technique and times were reviewed in the PA group. RESULTS: The average Society of Thoracic Surgeons (STS) risk assessment was 1.3 in both groups. Observed mortality was 0.9%. Complications of stroke, perioperative myocardial infarction, and atrial fibrillation were not significantly different between the two groups. Reoperation for bleeding was more likely in the PA group, while infections were more likely in the sternotomy group (p < 0.05). Transfusion requirements and postoperative length of stay were lower in the PA group (p < 0.05). CONCLUSIONS: Early results were similar between these two low-risk cohort groups. These findings support continued careful use of port-access revascularization in low-risk patients. Close follow-up of outcomes is essential to define the appropriateness of port-access techniques in patients requiring surgical revascularization.

Is occupational organic solvent exposure a risk factor for scleroderma?

OBJECTIVE: The primary objective was to determine whether occupational exposure to organic solvents is related to an increased risk of systemic sclerosis (SSc; scleroderma). METHODS: Occupational histories were obtained from 178 SSc patients and 200 controls. Exposure scores were computed for each individual using job exposure matrices, which were validated by an industrial expert. RESULTS: Among men, those with SSc were more likely than controls to have a high cumulative intensity score (odds ratio [OR] 2.9, 95% confidence interval [95% CI] 1.1-7.6) and a high maximum intensity score (OR 2.9, 95% CI 1.2-7.1) for any solvent exposure. They were also more likely than controls to have a high maximum intensity score for trichloroethylene exposure (OR 3.3, 95% CI 1.0-10.3). Among men and women, significant solvent-disease associations were observed among SSc patients who tested positive for the anti-Scl-70 autoantibody; these trends were not observed among the men and women who tested negative for anti-Scl-70. CONCLUSION: These results provide evidence that occupational solvent exposure may be associated with an increased risk of SSc.

Comparison of methods to assess coronary heart disease prevalence in South Asians.

BACKGROUND: Migrants from the Indian subcontinent (South Asian migrants) in the United Kingdom have high mortality from coronary heart disease (CHD) in comparison to the indigenous population. Few studies have assessed the prevalence of CHD in South Asians, and the applicability of conventional survey methods in this population is not known. In this pilot random population survey of South Asian men and women living in West London, the prevalence of CHD as judged by the Rose questionnaire, past cardiac history, cardiologist and resting electrocardiogram were compared. METHODS: Subjects aged 30-64 years from randomly selected households were invited for a cardiological assessment. A lay person administered the Rose questionnaire and recorded the past cardiac history. A cardiologist also made an independent assessment and a 12-lead electrocardiogram was recorded and analysed according to the Minnesota code. RESULTS: Three hundred and seventy-six individuals (192 men and 184 women) were assessed. The prevalence of angina in men and women, respectively, was 3.1% and 4.9% by the Rose questionnaire; 2.6% and 2.2% by past cardiac history; and 4.2% and 0.5% according to the cardiologist. The prevalence of myocardial infarction in men and women, respectively, was 5.2% and 2.2% by the Rose questionnaire, 3.6% and zero by past cardiac history and 3.6% and 0.5% by the cardiologist. Q/QS codes were present in 1.6% men and 0.5% women and ischaemic codes in 13% men and 14% women. Ischaemic changes were not associated with any cardiac history in 72% of men and 92% of women. For a diagnosis of CHD in men, there was poor agreement between the Rose questionnaire and either the past cardiac history or the cardiologist's assessment, but moderate agreement between the past cardiac history and the cardiologist. Agreement was poor between all three methods for a positive diagnosis of CHD in women. CONCLUSION: Current accepted epidemiological methods for assessing CHD prevalence may be inaccurate in South Asians, especially women. Electrocardiogram abnormalities suggestive of ischaemia are common in South Asians and are usually not associated with evidence of CHD. Thus, their value as indicators of CHD is questionable.