Cancer and hereditary haemochromatosis

Sir, In their recent review,¹ Limdi et al. appear to have understatedthe frequency of cancer in patients with hereditary haemochromatosis(HH).     

The prevalence of symptomatic, diabetic neuropathy in an insulin-treated population

The prevalence of symptomatic sensorimotor polyneuropathy has been determined in a population of 382 insulin-treated diabetic subjects aged 15-59 yr. Forty-one subjects (10.7%) were found to have diabetic neuropathy, according to strict diagnostic criteria that required the presence of symptoms and signs of nerve dysfunction in the absence of peripheral vascular disease. There was a significant correlation between glycosylated hemoglobin levels and motor conduction velocity in the median and peroneal nerves in all subjects. This finding further emphasizes the importance of metabolic factors related to hyperglycemia in the impaired nerve function seen in diabetic patients.     

The prevalence of and factors associated with diabetic retinopathy in the Australian population

OBJECTIVE: To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged > or =25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants. RESULTS: Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA(1c), and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis. CONCLUSIONS: This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.     

Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes

BACKGROUND: Hereditary haemochromatosis (HH) is a common autosomal recessive disease. Recently, HH heterozygosity has been identified as an independent risk factor for myocardial infarction and cardiovascular mortality. Iron may play an important role in atherogenesis by catalyzing peroxidation of low-density-lipoprotein (LDL), an essential step in atherogenesis. In iron overload conditions, non-transferrin-bound iron (NTBI) is found in serum, which can catalyze lipid peroxidation. We investigated whether sera of HH heterozygotes contain more NTBI than sera of normal controls. METHODS: In 27 treated HH homozygotes, 22 HH heterozygotes and 17 healthy control subjects, conventional parameters of iron status (serum iron, transferrin saturation, serum ferritin) were measured. NTBI was detected using HPLC after addition of nitrilotriacetic acid and pretreatment with cobalt. RESULTS: The conventional parameters of iron status were similar in the HH heterozygous group and the control group. NTBI was significantly higher in homozygotes compared to heterozygotes (1.79 micromol L-1 vs. 0.51 micromol L-1, 95% CI of the difference = 0.6-1.95, P < 0.001), and controls (1.79 micromol L-1 vs. - 0.3 micromol L-1, 95% CI of the difference = 1.36-2.81, P < 0.001). The difference in NTBI between the heterozygous subjects and control subjects was also significant (0.51 micromol L-1 vs. - 0. 3 micromol L-1, 95% CI of the difference = 0.05-1.57, P < 0.05). CONCLUSION: Phlebotomy treated HH homozygotes maintain a high and potentially harmful serum NTBI. HH heterozygotes have a higher serum NTBI than normal controls. The reported increased risk of cardiovascular events in heterozygous haemochromatosis may be explained by NTBI-catalyzed LDL peroxidation.     

The prevalence of pain complaints in a general population

The authors argue that the study of the complaint of pain falls within the purview of epidemiological study. An analytic survey of 500 randomly selected households on the roster of a group family practice clinic was undertaken. The purpose was to determine the self-reported prevalence rates of any pain complaint and to determine the distribution of pain rates according to selected demographic and socioeconomic variables. Sixteen percent of the individuals sampled from a family practice (H.S.O.) had experienced pain within the 2 weeks preceding the survey. The prevalence rate of those with persistent pain was approximately twice that of those with temporary pain. More women than men reported temporary and persistent pain. The age specific morbidity rate for persistent pain increased with age. The back, lower extremities, and head and face were the most frequently identified sites of pain in both subgroups. Persons with persistent pain used health services, both community physicians and hospital care, more frequently than did those with temporary pain. No significant differences between the two groups were reported for physical, social or emotional function although the persistent pain group characterized their general health status more poorly.     

The prevalence of bowel problems reported in a palliative care population

ContextConstipation and other disturbances of bowel function are distressing problems for people with specialist palliative care needs. Recent observations suggest that such problems may worsen as people become more unwell, but the changes in intensity over time are not well documented.ObjectivesThe objectives of this work were to understand the prevalence, intensity, and progression of self-reported bowel disturbances across a community palliative care population, which included people with cancer and noncancer diagnoses.MethodsAll people referred to a community-based palliative care service over a period of 6.3 years had their bowel problem scores reported, using a numerical rating score at every clinical encounter until their death, at four discrete time points, namely, 90, 60, 30, and seven days before death. This allowed change over three time periods to be considered. At the same time, other symptom scores were collected including nausea, fatigue, pain, appetite problems, and breathing problems. Patients were categorized according to the underlying disease that accounted for their referral to palliative care, namely, cancer diagnoses (upper gastrointestinal cancers, lower gastrointestinal cancers, cancers of the associated digestive organs, and other cancers) and nonmalignant diagnoses. Group differences over the time periods were assessed using analysis of variance. Bivariate analysis was used to explore the relationship between bowel disturbances and other symptoms using Spearman's Rho correlation.ResultsFor 7772 patients, data were collected an average of 22.5 times, generating 174,783 data collection points over an average of 98.6 days on the service. At the time of referral to the service, 3248 (42.4%) people had disturbed bowel scores, 548 (7.2%) of whom described these as severe. Only 1020 (13.1%) people never described disturbed bowel function over their time in palliative care. At each time point, approximately one-third were experiencing disturbed bowel function, with proportionally greater numbers of people experiencing more significant problems as death approached (Χ² (9) = 119.3; P < 0.001). Most referrals to the service were because of cancer diagnoses, with no significant differences noted between the bowel disturbance scores of those with cancer diagnoses compared with those with nonmalignant disease. Associations between bowel problem score and appetite problems, nausea, breathing problems, fatigue, and pain were explored. Although weak, there were statistically significant associations between all symptoms and bowel problem scores except for breathing problems.ConclusionIn conclusion, disturbed bowel function consistently remains a problem for people under the care of palliative care services, with the proportion of people with severe problems increasing as death approaches. This is despite the time and number of interventions currently used to palliate these problems.     

High prevalence of non-HFE gene-associated haemochromatosis in patients from southern Italy.

Hereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the HFE gene (C282Y and H63D) have been described in haemochromatosis patients. Epidemiological studies have revealed a strict association between hereditary haemochromatosis and C282Y homozygosis or C282Y/H63D compound heterozygosis, suggesting that these mutations may provide a useful tool for diagnosis. However, recent investigations from southern Europe have reported lower allelic frequencies of the C282Y mutation among haemochromatosis patients, apparently depending on the geographical area of the population analysed. To assess the predictive value of the detection of the C282Y and H63D HFE mutations in our geographical area, we have evaluated their occurrence in 46 haemochromatosis patients from southern Italy. We found that only 19.6% of our patients were homozygous for the C282Y mutation and 21.7% were compound C282Y/H63D heterozygotes. Among the remaining 59%, approximately 40% did not display any of the known HFE mutations. We conclude that, in southern Italy, another genetic determinant/s must be responsible for many haemochromatosis cases and that a genetic screening for the C282Y and H63D HFE mutations is not sufficient for hereditary haemochromatosis diagnosis.     

The relationship between diabetic autonomic neuropathy and diabetic risk factors in a Taiwanese population

This study looked at spectral analysis of heart rate variability (HRV) between patients with type 2 diabetes mellitus (DM) and healthy controls. The association between diabetic autonomic neuropathy (DAN) with HRV parameter changes and DM risk factors (including nephropathy) was investigated. HRV parameters were compared between 271 patients with DM and 160 controls. A statistically significant difference was found between the two groups for each parameter. Patients with DM were then divided into three groups by the levels of individual risk factors: body mass index, total cholesterol, 2-h postprandial plasma glucose concentration, glycosylated haemoglobin, duration of DM and the albumin-creatinine ratio. HRV parameters decreased significantly in patients with DM as the risk factor level progressed. This study identified previously known and new potential risk factors for the development of DAN, which may be important for the development of risk reduction strategies.     

The prevalence of pain in a pediatric and young adult cancer population

The prevalence and nature of pain in the population of children and young adults with malignancy treated by the Pediatric Branch of the National Cancer Institute were assessed over a 6 month period. One hundred and thirty-nine patients were evaluated during 161 in-patient days and 195 out-patient clinic visits. Approximately 50% of the patients assessed in the hospital and 25% of the patients assessed in the out-patient clinic were found to be experiencing some degree of pain at the time of assessment. Therapy-related pain predominated in both in-patients and out-patients; only one-third of the pain experienced by in-patients and less than 20% of the pain experienced by out-patients was due to tumor. Tumor pain was due primarily to bony invasion. In order to control pain in those individuals experiencing pain, narcotic analgesics were being used by one-half of the in-patients and one-third of the out-patients. Overall pain control was good, with the medium visual analogue scale score being 26 mm on a 0-100 mm scale. During the study period 7 patients were identified to have chronic pain for greater than 1 year following eradication of all known tumor from the site of pain. One was receiving massive doses of narcotics (120 mg/day of methadone) apparently out of proportion to his underlying pain.     

The spectrum of meningitis in a population with high prevalence of HIV disease

We studied the spectrum of meningitis and impact of HIV infection retrospectively (8 months) and prospectively (5 months) in 284 adult patients with meningitis hospitalized in Soweto, South Africa. Tuberculous meningitis (TBM) was the most common cause of meningitis (25.4%) followed by acute bacterial meningitis (ABM; 22.5%), acute viral meningitis (14.1%) and cryptococcal meningitis (13%). The in-hospital mortality was &gt;40% in TBM, ABM, cryptococcal meningitis, the neurosurgery and the parameningeal/parenchymal groups. At least 37.3% of all patients were HIV-seropositive (only 67% of patients were tested). In at least 27% of the study group the meningitis was an AIDS-defining illness (TBM, cryptococcal meningitis). Only 56.2% of patients with ABM has positive cultures (CSF or blood), of which <it>Streptococcus pneumoniae</it> was by far the most frequently found organism (35.8%). The spectrum of meningitis in HIV-affected communities in Africa can be expected to change towards a predominance of TBM and cryptococcal meningitis.      

The prevalence of immunization to Duffy antigens in a population of known racial distribution

A retrospective study at our hospital determined the race or ethnicity of patients seen in an 8-year period who had formed antibodies to Duffy antigens. During that time, 9876 serologic investigations had been performed as a result of a positive direct or indirect antiglobulin test. Among these samples, sera from 45 previously transfused or pregnant patients contained anti-Fya and two contained anti-Fy3. Twenty-nine of the sera that contained anti-Fya (62%) were from blacks, 12 (25%) were from whites, and 6 (13%) were from Hispanics. Both examples of anti-Fy3 were made by black patients. Red cells (RBCs) from 21 of the black patients were Fy(a-b-), those from 7 were Fy(a-b+), and those from 1 could not be phenotyped. RBCs from 17 of the non-black patients were Fy(a-b+) and those from 1 could not be phenotyped. The population of transfused patients evaluated in this study was 47 percent black, 29 percent white, and 24 percent Hispanic. Calculations based on an expected Fy(a-) frequency of 88 percent in blacks, 33 percent in whites, and 20 percent in Hispanics predict that the racial makeup of the Fy(a-) population at our hospital would be 73 percent black, 18 percent white, and 9 percent Hispanic, which is not significantly different (p = 0.25) from the racial makeup of the patients forming anti-Fya and -Fy3. These data indicate that blacks make antibodies to Duffy antigens as frequently as non-blacks.     

Diabetic retinopathy: contemporary prevalence in a well-controlled population

OBJECTIVE: To measure the extent to which modern intensified risk factor control has lessened the duration-specific prevalence of diabetic retinopathy and, therefore, has decreased the risk of blindness in Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS: Intensified control of blood glucose and blood pressure has prevented diabetic retinopathy in randomized controlled trials. There is as yet no confirmation that subsequent treatment intensification in the community has had the same result. We identified all 6993 members of a health maintenance organization, Kaiser Permanente Northwest (KPNW), who, in 1997-1998, had dilated retinal examinations and verifiable data of diagnosis of type 2 diabetes. We plotted prevalence by time since diagnosis for background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR) and compared these results to identically derived 1980-1982 results from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We estimated multivariate predictive models. RESULTS: Mean (+/- SD) HbA(1c) in KPNW was 7.84 +/- 1.26% versus 10.37% (standardized) in the WESDR. KPNW blood pressure averaged 138.6 +/- 13.8/79.5 +/- 7.4 mmHg compared with 147.0/79.0 in the WESDR. BDR was much less prevalent in KPNW, but PDR prevalence appeared unchanged. BDR preceded diagnosis in 20.8% of the WESDR subjects but only 2.0% of KPNW subjects. However, in both populations, the first cases of PDR appeared similarly, soon after diagnosis. CONCLUSIONS: Earlier diagnosis and more aggressive control of blood glucose and blood pressure decreased the duration-adjusted prevalence of background, but not of sight-threatening proliferative retinopathy. More population-based research is needed to replicate and explain this unexpected finding. Detecting and treating PDR should not be neglected on the assumption that risk-factor control has minimized its prevalence.     

The prevalence of pain in a general population. The results of a postal survey in a county of Sweden

In a postal survey, we asked 1009 randomly chosen individuals, age 18-84, about their pain problems. The pain prevalence depended on what types of questions were asked. Any pain or discomfort, including even a problem of short duration, was reported by 66% of those questioned. Forty percent reported 'obvious pain' (pain which affected them 'to quite a high degree' or more and was 'like being stiff after exercise' or worse) lasting more than 6 months. Pain problems of more than 6 months duration were reported far more often than short-lasting problems. Continuous or nearly continuous pain problems were reported as frequently as problems recurring regularly or irregularly. Pains in the neck, shoulders, arms, lower back and legs were most frequent. The prevalence of 'obvious pain' in these localizations was 15-20%. Pain was reported most frequently in the age group 45-64, where the prevalence of 'obvious pain' was 50% among males as well as females. Over 65 years of age the prevalence was less.