Fetal alcohol spectrum disorders

Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse.     

Predictors of Congestive Heart Failure after Treatment with an Endothelin Receptor Antagonist

Background and objectives

The Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death (ASCEND) trial tested the renoprotective effect of the endothelin receptor antagonist avosentan in patients with diabetes and nephropathy, but the study was terminated due to an excess of congestive heart failure (CHF) events in the avosentan arms, likely due to fluid retention. The aim of this study was to identify risk markers of CHF after treatment with avosentan.

Design, setting, participants, & measurements

In a post hoc analysis of the ASCEND trial (N=1392 participants), we assessed which baseline characteristics predicted CHF risk during avosentan treatment. Furthermore, postrandomization changes between baseline and the first available measurement of body weight and hemoglobin were examined as potential clinical indicators of fluid retention for their relationship with CHF development.

Results

Relative to placebo, avosentan increased CHF risk (hazard ratio, 2.76; 95% confidence interval, 1.68 to 4.54). The avosentan-related CHF risk was higher with lower baseline cholesterol levels (P interaction=0.003) and concomitant statin use (P interaction=0.06), whereas it was lower with a lower estimated GFR (P interaction=0.04). Patients allocated to avosentan had a median body weight increase of 0.6 kg (interquartile range, 0.0 to 2.0 kg) and a median hemoglobin decrease of 1.4 g/dl (interquartile range, −2.1 to −0.7 g/dl) at the first postrandomization measurement. The body weight increase induced by avosentan was associated with CHF development (P interaction=0.04), whereas hemoglobin decrease was not (P interaction=0.64). The increase in body weight was particularly pronounced in patients with a cardiovascular disease history and in patients using statins.

Conclusions

In avosentan-treated patients, body weight increase, but not hemoglobin decrease, was associated with CHF development, indicating that close body weight monitoring could provide an early signal of CHF development in future trials with endothelin receptor antagonists.     

Internists’ Attitudes About Assessing and Maintaining Clinical Competence

BACKGROUND

Important changes are occurring in how the medical profession approaches assessing and maintaining competence. Physician support for such changes will be essential for their success.

OBJECTIVE

To describe physician attitudes towards assessing and maintaining competence.

DESIGN

Cross-sectional internet survey.

PARTICIPANTS

Random sample of 1,000 American College of Physicians members who were eligible to participate in the American Board of Internal Medicine Maintenance of Certification program.

MAIN MEASURES

Questions assessed physicians’ attitudes and experiences regarding: 1) self-regulation, 2) feedback on knowledge and clinical care, 3) demonstrating knowledge and clinical competence, 4) frequency of use and effectiveness of methods to assess or improve clinical care, and 5) transparency.

KEY RESULTS

Surveys were completed by 446 of 943 eligible respondents (47 %). Eighty percent reported it was important (somewhat/very) to receive feedback on their knowledge, and 94 % considered it important (somewhat/very) to get feedback on their quality of care. However, only 24 % reported that they receive useful feedback on their knowledge most/all of the time, and 27 % reported receiving useful feedback on their clinical care most/all of the time. Seventy-five percent agreed that participating in programs to assess their knowledge is important to staying up-to-date, yet only 52 % reported participating in such programs within the last 3 years. The majority (58 %) believed physicians should be required to demonstrate their knowledge via a secure examination every 9–10 years. Support was low for Specialty Certification Boards making information about physician competence publically available, with respondents expressing concern about patients misinterpreting information about their Board Certification activities.

CONCLUSIONS

A gap exists between physicians’ interest in feedback on their competence and existing programs’ ability to provide such feedback. Educating physicians about the importance of regularly assessing their knowledge and quality of care, coupled with enhanced systems to provide such feedback, is needed to close this gap.     

Informed Consent for Medical Research: Common Discrepancies and Readability

Objective: To identify common discrepancies and average reading grade levels for informed consent forms (ICFs) us submitted to institutional review boards (IRBs) by medical researchers.
Methods: A retrospective evaluation of ICFs as submitted to IRBs of 3 university-affiliated hospitals during a I-year period. ICF content was evaluated using a checklist of 23 requirements specified in the federal regulations governing human research. Documents then were computer-analyzed to determine the readability scores using 2 common indexes of comprehension. A discrepancy was defined as any instance in which an ICF did not address an applicable requirement in the Code of Federal Regulations.
Results: Eighty-two ICFs representing 16 medical specialties were evaluated; 8 (10%) were from emergency medicine. Eighteen ICFs (22%) were conspicuously incomplete, lacking 29 federal requirements. The mean number of discrepancies was 4.7 (95% CI, 3.9–5.5) Common omissions included: a statement about who is doing the research, number of subjects in the study, circumstances when a subject's participation may be terminated, disclosure of alternative procedures, and notice to subjects regarding new findings. The mean Flesch grade level required to read all ICFs was 13.8 (95% CI, 13.5–14.2), implying that the majority of the U.S. adult population would be unable to comprehend these forms.
Conclusion: Designing a consent form to meet all of the federal requirements while maintaining a level of reading comprehension suitable for the general population is a difficult task for investigators.     

Effect of Al-chlorophenoxyisobutyrate (Alufibrate) on pyruvate metabolism and on the fate of very low density lipoprotein lipids in hyperlipidemic patients

he exhalation of total CO₂ and ¹⁴ CQ₂ after an intravenous injection of either [1-¹⁴C]- or [2-¹⁴C]pyruvate was measured in six male patients with type IV hyperlipidemia who had previously been receiving treatment with alufibrate or placebo. Considerably more ¹⁴ CO₂ was exhaled after the injection of [1-¹⁴C]pyruvate than after the injection of [2-¹⁴C] pyruvate. Treatment with alufibrate only slightly diminished the oxidation of [1-¹⁴C]-pyruvate, but increased the oxidation of [2-¹⁴C] pyruvate to ¹⁴CO₂ by 25%. The total concentrations of [2-¹⁴C] pyruvate and its incorporation into the lipids of lipoprotein fractions were measured over 24 h. Alufibrate treatment decreased the serum concentration of VLDL by 53%, by reducing the turnover rate by 25% and increasing the net removal rate by about 30%. No effects on LDL and HDL lipid fractions were detected.     

A comparison of two microcomputer-based programs for bibliographic retrieval and formatting

We evaluated two representative microcomputer-based programs for organizing a biomedical literature filing system. With a bibliography of 100 anesthetic references, a series of benchmark tests was developed to measure the speed and accuracy of typical searching, sorting, and formatting tasks. Each program performed the searching tasks accurately and at about the same speed. One program performed sorting without errors, provided the field order of the template used to enter references was unchanged. Both programs used punctuation files, that is, templates for controlling author presentation; punctuation to suit style requirements of individual journals; and order of particular fields, such as publisher and year of publication. Each program was able to format journal, book, and chapter references correctly, but the resulting output required some refining in a word processor. Both require a major time commitment to learn and to create custom punctuation files for journals not included in the predesigned punctuation files. Once mastered, both programs are quite competent at organizing reprints and formatting journal references.     

Lack of efficacy of high-dose verapamil in preventing brain damage in baboons and pigs after prolonged partial cerebral ischemia

There has been mounting speculation that calcium antagonists may be useful in reducing or preventing brain damage after cardiopulmonary resuscitation. To test the clinical usefulness of these agents in averting such damage, high-dose verapamil was administered to baboons and pigs after partial cerebral ischemia for varying periods of time. In Group A baboons and pigs, the major aortic branches supplying the carotid and vertebral circulations were clamped for periods ranging from 15 to 150 minutes, and neurological recovery was observed. In Group B, verapamil hydrochloride 0.7 mg/kg was given by intravenous infusion after similar periods of arterial occlusion. The administration of verapamil did not lead to any clinically improved neurological outcome. The use of verapamil after prolonged periods of partial cerebral ischemia did not improve neurological recovery in baboons and pigs.     

Percutaneous biliary drainage in acute suppurative cholangitis

One hundred and sixteen percutaneous drainage procedures of the biliary system were performed in a 2-year period. Eight of 9 acutely ill patients with the diagnosis of acute suppurative cholangitis were successfully treated nonoperatively. They represented 26% of all patients with benign or postsurgical obstruction referred for biliary decompression. Conversely, acute suppurative cholangitis only occurred in 2.3% of patients with underlying malignant disease. These observations are considered most relevant in predicting the purulent nature of the disease, with further implications for patient management. Early recognition and prompt decompression of the biliary system are mandatory, along with the appropriate antibiotic coverage. Our experience compares favorably with surgical results and the procedure is proposed as the method of choice for the initial treatment of acute suppurative cholangitis.