Ramon Velez

Risk of Cirrhosis and Primary Liver Cancer in Alpha1-Antitrypsin Deficiency

Previous reports have suggested an association between homozygous alpha 1-antitrypsin deficiency, cirrhosis, and primary liver cancer. To assess the risk of these complications we conducted a retrospective study based on 17 autopsied cases of alpha 1-antitrypsin deficiency identified during the period 1963 to 1982 in the city of Malmö, Sweden. During the study period, autopsies were performed in 38,250, or 68.2 percent, of all patients in the city who died. From the homozygote frequency in the population, 21 of these were expected to have alpha 1-antitrypsin deficiency. The disease had been diagnosed in 20, and autopsies had been performed in 17 (1 child and 16 adults). Each autopsied case was matched with four controls selected from the same autopsy register, and the Mantel-Haenszel odds ratio (ORmh) was calculated. The results indicated a strong relation between alpha 1-antitrypsin deficiency and cirrhosis (ORmh = 7.8; 95 percent confidence limits, 2.4 to 24.7) and primary liver cancer (ORmh = 20; 95 percent confidence limits, 3.5 to 114.3). When data were stratified according to sex, these associations were statistically significant only for male patients. We conclude that men with alpha 1-antitrypsin deficiency may be at higher risk for cirrhosis and primary liver cancer. The apparent male predominance suggests the additive effects of exogenous factors.

Quality-of-Life Changes and Hearing Impairment: A Randomized Trial

OBJECTIVE To assess whether hearing aids improve the quality of life of elderly persons with hearing loss. SETTING Primary care clinics at a Bureau of Veterans Affairs hospital. PATIENTS One hundred and ninety-four elderly veterans who were identified as being hearing impaired from a screening survey involving 771 consecutive clinic patients. Of the original 194, 188 (97%) completed the trial. INTERVENTION Subjects were randomly assigned to either receive a hearing aid (n = 95) or join a waiting list (n = 99). MAIN ENDPOINTS: A comprehensive battery of disease-specific and generic quality-of-life measures were administered at baseline, 6 weeks, and 4 months. MEASUREMENTS AND MAIN RESULTS Persons assigned to the two groups were similar in age, ethnicity, education, marital status, occupation, and comorbid diseases. At baseline, 82% of subjects reported adverse effects on quality of life due to hearing impairment, and 24% were depressed. At follow-up, a significant change in score improvements for social and emotional function (34.0; 95% CI, 27.3 to 40.8; P less than 0.0001), communication function (24.2; CI, 17.2 to 31.2; P less than 0.0001), cognitive function (0.28; CI, 0.08 to 0.48; P = 0.008), and depression (0.80; CI, 0.09 to 1.51; P = 0.03) was seen in subjects who received hearing aids compared with those assigned to the waiting list. Six drop-outs (three per group), no crossovers, and no significant changes in cointerventions were seen. Average, self-reported, daily aid use in the hearing aid group was 8 hours. CONCLUSION Hearing loss is associated with important adverse effects on the quality of life of elderly persons, effects which are reversible with hearing aids.

Association Between Hearing Impairment and the Quality of Life of Elderly Individuals

Hearing impairment is one of the most common chronic health problems of elderly Americans. Although adverse effects on quality of life are thought to be considerable, they have not been rigorously evaluated. This study was designed to identify the types and extent of dysfunction experienced by elderly individuals with hearing loss, and to define the most appropriate measures for assessing this dysfunction. Elderly male veterans attending a primary care clinic were screened for hearing loss and had their quality of life assessed with a comprehensive battery of disease‐specific and generic measures. Of 472 people who had their hearing tested, 106 had hearing loss. Hearing loss was associated with significant emotional (P = .0001), social (P = .0001), and communication (P = .02) dysfunction. Most individuals (66%) perceived these dysfunctions as severe handicaps even though audiologic loss revealed only mild to moderate impairment (pure tone average loss, 27–55 dB). Adverse effects were best detected with disease‐specific rather than generic functional status measures. We conclude that hearing impairment is associated with important adverse effects on the quality of life of elderly individuals, and that these effects are perceived as severe handicaps even by individuals with only mild to moderate degrees of hearing loss.

Screening for Diabetic Retinopathy: The wide-angle retinal camera

OBJECTIVE— To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS— Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physicians assistant through dilated pupils using direct ophthalmoscopy, a single 45° retinal photograph without pharmacological dilation, and a set of three dilated 45° retinal photographs) were compared with a reference standard of stereoscopic 30° retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS— The subjects (352) had complete exams excluding the exam by the physicians assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physicians assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS— Fundus photographs taken by the 45° camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45° camera.

Patterns of Improved Survival in Patients With Multiple Myeloma in the Twenty-First Century: A Population-Based Study

PURPOSE Randomized multiple myeloma (MM) studies show improved response rates and better progression-free survival for newer therapies. However, a less pronounced effect has been found for overall survival (OS). Using population-based data including detailed treatment information for individual patients, we assessed survival patterns for all patients diagnosed with MM in Malmö, Sweden from 1950 to 2005. PATIENTS AND METHODS We identified 773 patients with MM (48% males). On the basis of the age limit used for treatment with high-dose melphalan with autologous stem-cell support (HDM-ASCT; < or = 65 years old) in Sweden, we constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years old or younger and patients older than 65 years. Results Including all age groups, patients diagnosed from 1960 to 1969 had a better survival than patients diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS increased from 24.3 to 56.3 months (P = .036) in patients < or = 65 years old. In contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7 months, P = .7). CONCLUSION With the establishment of HDM-ASCT as the standard therapy for younger patients with MM, OS has improved significantly for this age group in the general MM population. With novel therapies being commonly used at disease progression, presumably it becomes increasingly difficult to confirm survival differences between defined induction, consolidation, and maintenance therapies in the future. Consequently, in the era of novel MM therapies, population-based studies will serve as a necessary complement to randomized trials.

Patterns of Multiple Myeloma During the Past 5 Decades: Stable Incidence Rates for All Age Groups in the Population but Rapidly Changing Age Distribution in the Clinic

OBJECTIVE To define age-adjusted incidence trends in multiple myeloma (MM) in a well-characterized population during a long period, given that some, but not all, studies have reported increasing MM incidence over time and that clinical experience from some centers suggests an increased incidence mainly in younger age groups. PATIENTS AND METHODS We identified all patients (N=773) with MM diagnosed in Malmö, Sweden, from January 1, 1950, through December 31, 2005. Using census data for the population of Malmö, we calculated age- and sex-specific incidence rates. Incidence rates were also calculated for 10-year birth cohorts. Analyses for trends were performed using the Poisson regression. RESULTS From 1950 through 2005, the average annual age-adjusted (European standard population) incidence rate remained stable (Poisson regression, P=.07 for men and P=.67 for women). Also, comparisons between 10-year birth cohorts (from 1870-1879 to 1970-1979) failed to detect any increase. Between 1950-1959 and 2000-2005, the median age at diagnosis of MM increased from 70 to 74 years, and the proportion of newly diagnosed patients aged 80 years or older increased from 16% to 31%. CONCLUSION Our finding of stable MM incidence rates for all age groups during the past 5 decades suggests that recent clinical observations of an increase of MM in the young may reflect an increased referral stream of younger patients with MM, which in turn might be a consequence of improved access to better MM therapies. Importantly, because of the aging population, the proportion of patients with MM aged 80 years or older doubled between 1950-1959 and 2000-2005.

Cost-effectiveness of alternative methods for diabetic retinopathy screening

OBJECTIVE To assess from the perspectives of a government delivery system and patients, the cost-effectiveness of the 45-degrees retinal camera compared to the standard ophthalmologists exam and an ophthalmic exam by a physicians assistant or nurse practitioner technician, for detecting nonproliferative and proliferative diabetic retinopathy. RESEARCH DESIGN AND METHODS Comparison of 45-degrees fundus photographs with and without pharmacological pupil dilation taken by technicians and interpreted by experts, direct and indirect ophthalmoscopy by ophthalmologists, and direct ophthalmoscopy by technicians with seven-field stereoscopic fundus photography (reference standard). Costs were estimated from market prices and actual resource use. The study included 352 patients attending outpatient diabetes and general-medicine clinics at VA and DOD facilities. RESULTS Medical system costs per true positive were: 45-degrees photos with dilation,

Comparison of trends in the incidence of multiple myeloma in Malmö, Sweden, and other countries, 1950-1979

295; 45-degrees photos without dilation,

Increasing influenza immunization among high-risk patients: Education or financial incentive?

378; ophthalmologist,

Emergency medical transport of the elderly: A population-based study☆

390; and technician,