Improving medical personnel selection and appointment processes.

PURPOSE: This paper seeks to argue that processes for selecting and appointing medically qualified personnel in some healthcare organizations may be limited, especially those that emphasize qualifications rather than expanding the criteria to include practice scope, person-organization fit and capability to function within a healthcare team. DESIGN/METHODOLOGY/APPROACH: The paper is based on the authors' experiences and a literature review. FINDINGS: Selection based purely on academic merit, advanced clinical training, skills and professional achievements may not address other essential selection criteria. Medical personnel need to possess competencies such as ability to give high quality care and work constructively in a clinical team; communication skills; willingness to actively participate in quality and safety programs; teaching ability; management and leadership skills; and support institutional values and corporate aims. These attributes are often over-looked and cannot be assumed from academic merit and achievements. RESEARCH LIMITATIONS/IMPLICATIONS: The study's conclusions are based on the authors' experiences and literature review. Future studies may wish to examine selection technique efficacy and outcomes empirically. PRACTICAL IMPLICATIONS: Better medical personnel selection and appointment processes are likely to reduce unnecessary costs associated with poorly-made appointments, improve patient outcomes and may have a formative role encouraging medical personnel to take a broader view of their healthcare organization roles. ORIGINALITY/VALUE: The authors challenge selection panel members to consider non-traditional with normal selection criteria for medical appointments. Nine recommendations for enhancing selection processes are provided.

The changing role of liver biopsy in diagnosis and management of haemochromatosis.

Liver biopsy with histological examination of liver tissue was for many years the cornerstone of the diagnosis of haemochromatosis, allowing assessment of the degree of iron overload and examination of liver histology for the acute and chronic effects of iron overload. In the past two decades the role of liver biopsy in haemochromatosis has changed dramatically. Liver biopsy is rarely requested for two main reasons: (1) genetic testing for human haemochromatosis (HFE) mutations has proved to be very reliable in the diagnosis of haemochromatosis in Caucasian populations, and (2) the majority of patients with haemochromatosis are now diagnosed at an early stage well before permanent tissue damage occurs, so the need to assess tissue and organ damage has diminished. Liver biopsy continues to have a very important role in a small number of haemochromatosis patients for whom it has both diagnostic and prognostic implications. Liver biopsy is essential for the accurate assessment of patients with non-HFE haemochromatosis and in patients who have dual pathology. It is also useful where there appears to be a discrepancy between HFE genotypes and iron studies, particularly in HFE heterozygotes. Finally, liver biopsy is currently the 'gold standard' for the diagnosis of fibrosis and cirrhosis, although this is changing as non-invasive methods for assessing fibrosis become more reliable and available. Therefore, it is important that pathologists maintain their knowledge and skills in the use of liver biopsy in haemochromatosis and other iron storage disorders.

The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis.

BACKGROUND & AIMS: Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y substitution have been well characterized, the clinical significance of the C282Y/H63D state remains unclear. This study assessed the phenotypic expression in C282Y/H63D subjects as compared with C282Y homozygotes. METHODS: Data were obtained from 91 C282Y/H63D probands, 158 C282Y/H63D subjects identified through family screening, and 483 C282Y homozygotes. Subjects underwent clinical evaluation, genotyping, biochemical assessment, and liver biopsy examination where clinically indicated. RESULTS: C282Y/H63D probands had significantly less clinical and biochemical expression than C282Y homozygotes. Biochemical expression was higher in C282Y/H63D probands than in C282Y/H63D subjects identified through family screening (P < .001). Of the C282Y/H63D subjects with serum ferritin levels greater than 1000 mug/L, all had known comorbid factors that could have contributed to the increased ferritin level. Of the 51 C282Y/H63D subjects who underwent liver biopsy examination, significantly increased iron stores were present in 9 subjects and hepatic fibrosis was present in 13. Twelve of the 13 had evidence of hepatic steatosis, excess alcohol consumption, or diabetes. The mobilizable iron level was significantly higher in C282Y homozygous males than in compound heterozygous males (P < .001). Genetic screening of C282Y/H63D first-degree relatives detected 5 C282Y homozygotes. CONCLUSIONS: C282Y/H63D subjects referred for assessment had a high prevalence of increased iron indices but did not develop progressive clinical disease without comorbid factors such as steatosis, diabetes, or excess alcohol consumption. When fibrosis was seen, 1 or more comorbid factors almost always were present. Thus, phlebotomy therapy is warranted and cascade screening of relatives should be performed because expressing C282Y homozygotes may be detected.

Screening for hemochromatosis in asymptomatic subjects with or without a family history.

BACKGROUND: Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history. METHODS: We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years. RESULTS: Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively; hepatic fibrosis (stages 2-4) in 18.4% and 5.4%; and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic. CONCLUSIONS: Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.

Autosomal dominant hereditary sensory neuropathy with chronic cough and gastro-oesophageal reflux: clinical features in two families linked to chromosome 3p22-p24.

Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.

Probable ischemic colitis caused by pseudoephedrine with tramadol as a possible contributing factor.

OBJECTIVE: To report a case of acute self-limiting ischemic colitis in a patient who was self-medicating with a proprietary over-the-counter oral decongestant containing pseudoephedrine. CASE SUMMARY: A 46-year-old white man developed clinical, endoscopic, and histologic features of acute ischemic colitis after taking a proprietary oral decongestant containing pseudoephedrine 240 mg/day for one week. The total daily dose was at the upper limit of recommended doses for pseudoephedrine (as a single drug or in combination products). The patient was also taking tramadol 150 mg/day for chronic back pain. He made a complete recovery. There were no other explanations for the episode of ischemic colitis. DISCUSSION: An objective causality assessment based on the Naranjo probability scale revealed pseudoephedrine to be a probable cause of ischemic colitis in our patient. Pseudoephedrine occasionally causes vascular insufficiency due to intense vasoconstriction, even at standard doses. Although our patient was not taking an excessive dose of pseudoephedrine, it is possible that the concurrent use of pseudoephedrine and tramadol may have increased adrenergic vasoconstriction, predisposing to ischemic colitis. CONCLUSIONS: Prolonged or intensive use of medications containing pseudoephedrine should be avoided, and the package information should contain advice that the medication should be ceased if abdominal pain or other ischemic symptoms occur.

Ultrastructural changes in hepatic sinusoidal endothelial cells acutely exposed to colloidal iron.

Hepatic sinusoidal endothelial cells form an important interface between the vascular system, represented by the sinusoids, and the space of Disse that surrounds the hepatocyte microvilli. This study aimed to assess the light microscopic and ultrastructural effects of acute exposure of hepatic sinusoidal endothelial cells to colloidal iron by injection of rats with iron polymaltose. Eight minutes after a single intravenous injection of iron polymaltose sinusoidal endothelial cells showed defenestration, and thickening and layering as assessed by transmission electron microscopy. Kupffer cells and stellate cells appeared activated. These changes were not observed in control animals, experiments using equivalent doses of maltose, or experiments using colloidal carbon except for Kupffer cell activation due to colloidal carbon. No significant light microscopic changes were seen in study or control animals. The findings indicate that acute exposure to colloidal iron causes changes in hepatic sinusoidal endothelial cells, stellate cells and Kupffer cells. This may be the result of a direct toxic effect of iron or increased production of reactive oxygen species. These observations suggest a possible mechanism for defenestration of sinusoidal endothelial cells in ageing and in disease states.

Acute pancreatitis associated with angiotensin II receptor antagonists.

OBJECTIVE: To report a case of acute pancreatitis in a patient receiving a combination formulation of irbesartan and hydrochlorothiazide (HCTZ). CASE SUMMARY: A 33-year-old white woman developed acute pancreatitis 10 days after starting irbesartan 300 mg and hydrochlorothiazide 12.5 mg for treatment of hypertension. Her symptoms disappeared and serum concentrations of lipase and amylase returned to normal 2 days after irbesartan/HCTZ was discontinued. A search of MEDLINE (1990-September 2002) and the Australian Adverse Drug Reaction Advisory Committee database revealed 1 additional case of pancreatitis associated with irbesartan/HCTZ and 3 cases of pancreatitis associated with losartan. DISCUSSION: An objective causality assessment indicates that it is probable that pancreatitis was caused by the angiotensin II receptor antagonist irbesartan (and the same is probably true for losartan). It is less likely that the hydrochlorothiazide in irbesartan/HCTZ caused pancreatitis in our patient since the dose was lower than that usually associated with thiazide-induced pancreatitis. Angiotensin II receptors are thought to be important in regulation of pancreatic secretion and microcirculation, but the mechanism of pancreatitis induced by angiotensin II receptor antagonists remains unclear. CONCLUSIONS: Clinicians should be aware that irbesartan/HCTZ or losartan may cause acute pancreatitis. If abdominal pain develops, the medication should be discontinued and the patient investigated for acute pancreatitis.

Unsaturated iron binding capacity and transferrin saturation are equally reliable in detection of HFE hemochromatosis.

OBJECTIVE: Unsaturated iron binding capacity (UIBC) has been proposed as an inexpensive alternative to transferrin saturation for detection of hereditary hemochromatosis. The aim of this study was to compare, in a hospital referral clinic, the reliability of transferrin saturation and UIBC for detection of subjects who have inherited HFE (HLA-asociated iron overload) genotypes predisposing to iron overload. METHODS: Serum transferrin saturation, UIBC, and ferritin were tested in 110 consecutive subjects. Optimum thresholds were determined from receiver operating characteristic curves. RESULTS: Of 110 subjects, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). In genetically predisposed subjects with biochemical expression, the optimum threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and specificity 0.95. For UIBC, the optimum threshold was 143 microg/dL (25.6 micromol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients referred with a family history or clinical suspicion of hemochromatosis, transferrin saturation and UIBC were highly reliable predictors of genotype. In patients referred for investigation of abnormal liver enzymes without a known family history of hemochromatosis, a normal transferrin saturation or normal UIBC was highly reliable in excluding hemochromatosis. CONCLUSIONS: Transferrin saturation and UIBC have equal reliability in ability to predict hemochromatosis. UIBC should be considered as an alternative to transferrin saturation in detection of hemochromatosis.

Genetic testing for HFE hemochromatosis in Australia: the value of testing relatives of simple heterozygotes.

BACKGROUND: It is unclear whether screening of relatives of C282Y and H63D heterozygotes (other than compound heterozygotes) for hemochromatosis will detect sufficient numbers of cases to justify introduction of this screening strategy. METHODS: Conditional probabilities were determined using published Australian allele frequencies and penetrance data to determine the detection rate of hemochromatosis by testing the siblings and offspring of heterozygotes (subjects with only one HFE mutation). RESULTS: The number of individuals who are at risk of developing increased body iron stores because of HFE mutations is substantially higher (1 in 80) than previously estimated. In addition, 33% of the Australian population are heterozygous for either C282Y or H63D. Based on population estimates, the relative risk to the offspring of C282Y and H63D heterozygotes of developing increased iron stores is 4.1 and 1.5, respectively, while the relative risk to each sibling is 2.3 and 1, respectively. The risk of developing clinical features of hemochromatosis or hepatic fibrosis is likely to be substantially lower. CONCLUSIONS: Although the detection rate from testing the families of unaffected heterozygotes is low, this can be justified as a clinically useful screening strategy. At the present time this strategy should be restricted to first-degree relatives of heterozygotes. Further studies are recommended to determine if cascade genetic screening is a cost-effective alternative to general population screening.