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PubMed2006

Slower disease progression and prolonged survival in contemporary patients with amyotrophic lateral sclerosis: is the natural history of amyotrophic lateral sclerosis changing?

BACKGROUND: In recent years, considerable effort has been made to improve the treatment of patients with amyotrophic lateral sclerosis (ALS). However, despite the increased use of supportive measures, controversy still exists about overall trends in disease progression and survival. OBJECTIVE: To analyze whether survival and disease progression in patients with ALS have changed during the past 20 years. DESIGN: By using the Kaplan-Meier life-table method, we compared disease progression (measured as time to a 20-point increase in the Appel ALS score) and survival in 1041 patients diagnosed as having ALS between January 1, 1984, and January 1, 1999 (historical group, n = 647), and between January 2, 1999, and November 1, 2004 (contemporary group, n = 394). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: The median survival from symptom onset was 4.32 years (95% confidence interval [CI], 3.81-4.84 years) in the contemporary group compared with 3.22 years (95% CI, 3.04-3.41 years) in the historical group (P<.001). The contemporary patients progressed more slowly (10 months to a 20-point increase; 95% CI, 9-13 months) compared with patients in the historical group (9 months to a 20-point increase; 95% CI, 8-9 months) (P<.001). In the multivariate Cox proportional hazards model, the observed outcome improvement over time was independent of confounding factors, such as age, sex, diagnostic delay, site of symptom onset, baseline forced vital capacity, and baseline Appel ALS score, and independent of the use of potentially outcome-modifying therapies (riluzole, noninvasive ventilation, and percutaneous gastrostomy). CONCLUSIONS: Contemporary patients had significantly prolonged survival and slower disease progression compared with patients from the historical group. The improved outcome seemed independent of specific ALS outcome-modifying therapies, but we cannot rule out an effect of comorbid conditions, which could have influenced medical treatment and survival. Nevertheless, our observations suggest the possibility that disease course has changed and that ALS is becoming less aggressive over time. Further studies are needed to determine whether there has been a fundamental change in the natural history of the disease or whether our results are because of other unmeasured aspects of improved multidisciplinary care.

Adult↗

PubMed1989

Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982.

In the period 1950 through 1982, there were 294 episodes of ocular herpes simplex virus infection in 151 residents of Rochester, Minn. Recurrence rates assessed by life-table methods after the first episode were 9.6% at 1 year, 22.9% at 2 years, and 63.2% at 20 years. Recurrence rates appeared to rise following repeated episodes. Ocular herpes simplex affecting both eyes at the same and/or different episodes was seen in 18 patients (11.9%). One fifth of patients had lid involvement alone, while a third had solely superficial corneal involvement. Deep corneal disease or uveitis was relatively uncommon. Therapy during the early period was varied, but significant complications were uncommon. Ninety percent of the eyes maintained visual acuity of 20/40 or better. The economic impact, measured in terms of days of active disease and physician visits, was substantial.

Adult↗

PubMed1990

Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Macular Photocoagulation Study Group.

The persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 247 eyes assigned to krypton red laser photocoagulation in the Age-Related Macular Degeneration Study-Krypton Laser were examined to describe the incidence, timing, visual impact, and potential risk factors for persistence and recurrence. Persistent neovascularization detected within 6 weeks of initial treatment was observed in 32% of treated eyes, and recurrent neovascularization was estimated by life-table methods to develop in an additional 47% over a 5-year period. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. The persistence rate among eyes having 10% or more of the foveal side of the neovascular membrane not covered by treatment was twice as high as in eyes having more extensive coverage. Patients having a fellow eye with a neovascular membrane or scar, a fellow eye with 20 or more drusen in the central macula, or a fellow eye with nongeographic atrophy at initial visit had more recurrences than patients without these characteristics. Ophthalmologists treating similar lesions may be able to reduce persistent neovascularization and the associated visual loss by covering the entire lesion with treatment.

Age Factors↗

PubMed1999

Recurrent gustatory sweating (Frey syndrome) after intracutaneous injection of botulinum toxin type A: incidence, management, and outcome.

OBJECTIVE: To evaluate the duration of effectiveness of intracutaneous injection of botulinum toxin type A for gustatory sweating as well as the incidence, severity, management, and outcome of recurrent gustatory sweating. DESIGN: An inception cohort with a minimum of 18 months of follow-up. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Thirty-three patients with severe gustatory sweating. INTERVENTION: Intracutaneous injection of 25 to 175 IU (mean, 86 IU) of botulinum toxin type A. MAIN OUTCOME MEASURES: Analysis of the effectiveness of the intracutaneous injection of botulinum toxin type A using the Kaplan-Meier actuarial life-table method; completion of the Minor starch-iodine test in patients without symptomatic recurrent gustatory sweating; and the patients' self-assessment of the severity of the recurrent gustatory sweating. RESULTS: The 1-, 2-, and 3-year actuarial estimate for symptomatic recurrent gustatory sweating was 27%, 63%, and 92%, respectively. In the 7 patients without symptomatic recurrent gustatory sweating, the Minor starch-iodine test revealed persistent gustatory sweating in 6, resulting in an overall 97% rate (32 of 33 patients) for recurrent gustatory sweating. No statistical relationship could be demonstrated between the duration of effectiveness, the incidence of recurrent gustatory sweating, the severity of recurrent gustatory sweating, and the following variables: age, sex, cause of gustatory sweating, skin surface involved, and dose of botulinum toxin type A injection. Within the group of 26 patients with symptomatic recurrent gustatory sweating, (1) the severity of the recurrent gustatory sweating was always reduced when compared with the severity of the initial gustatory sweating, and (2) the recurrent gustatory sweating always remained amenable to reinjection of botulinum toxin type A. CONCLUSIONS: The present series demonstrated a linear regression in the effectiveness of the intracutaneous injection of botulinum toxin type A in patients with gustatory sweating, while no factors appeared to be statistically related to the duration of effectiveness and/or the incidence of recurrent gustatory sweating. However, because the severity of recurrent gustatory sweating is reduced when compared with the severity of the initial gustatory sweating and because recurrent gustatory sweating remains amenable to reinjection of botulinum toxin type A, we believe that the intracutaneous injection of botulinum toxin type A should become the first-line treatment option in patients with gustatory sweating.

Adolescent↗

PubMed1983

Carcinoma of the tonsil. A retrospective analysis of prognostic factors.

A study was designed to assess clinical and pathologic variables with prognostic value in carcinoma of the tonsil. Seventy-nine cases, diagnosed and treated at the University Hospital of Montevideo, Uruguay, during a 20-year period (1960 through 1979) were studied. Survival of patients according to sex, age, performance status, tumor size (T), nodal status (N), clinical stage, tongue involvement, histologic type, grade of differentiation, and local control with treatment was analyzed with the life-table method and the statistical significance was estimated with the logrank test. Regression methods showed that the combination of T and N factors explained 25% of the prognosis. When local control was included in the equation, the predictive power increased to 52%. Local spread to the base of the tongue and female sex were of marginal significance regarding prognosis.

Actuarial Analysis↗

PubMed1990

Submandibular gland tumors. Adverse histologic factors and therapeutic implications.

We reviewed our 41-year experience with tumors of the submandibular gland to determine what factors influence outcome and their implications for treatment. The most common benign neoplasm was pleomorphic adenoma (21), while among malignant tumors the adenoid cystic variety (37) predominated. For the 86 patients who had malignant tumors, the 2- and 5-year survivals by the life table method were 82% and 69%, respectively. For patients with malignant tumors, histology, size, perineural invasion, and prior treatment did not affect overall survival. Factors adversely affecting outcome were extraglandular soft-tissue extension and lymph node metastasis. Local-regional control was enhanced in patients with soft-tissue extension if they were treated by surgery followed by radiotherapy rather than by surgery alone.

Adenocarcinoma↗

PubMed1978

Natural history of nonstenotic, asymptomatic ulcerative lesions of the carotid artery.

To define the natural history of the asymptomatic, nonstenotic, ulcerative lesion involving the carotid artery bifurcation, the arteriograms and clinical course of 67 patients with 72 asymptomatic ulcerative lesions of the carotid artery were reviewed. The angiographic appearance of ulceration was classified into three groups: minimal (group A), large (group B), and compound (group C). Using life-table methods, the clinical course of these patients was compared between groups and was also compared to a nonrandomized surgically treated group of patients with nonstenotic ulcerative lesions in whom operation was performed for hemispheric or monocular symptoms. There were no significant (P greater than .1) differences in mortality, but the differences in stroke incidence was highly significant (P less than .001). The annual stroke rate, averaged over seven years, was 0.4% per year for group A, 1.47% per year for the surgically treated group, and 12.5% per year for groups B and C. The data indicate that group A ulcers have a benign prognosis, in noticeable contrast to group B and C ulcers which incur a high risk for subsequent stroke.

Adult↗

PubMed1979

Use of umbilical vein graft as an arterial substitute.

Seventy reconstructions, 14 to the popliteal artery above the knee, 40 to the popliteal artery below the knee, and 16 to the tibioperoneal arteries were performed with the Dardik umbilical vein graft tanned in glutaraldehyde. Indications for use included absence of or inadequate saphenous veins, or for expediency during emergency or complex procedures. The cumulative patency rate (calculated by the life table method) for the total group was 77% at 18 months. The failures are further analyzed according to the type of procedure, the grade of disease, and the distal runoff vessel. Early failures were attributed primarily to poor runoff and not to intrinsic properties of the graft. Our overall experience with the umbilical vein graft has been good. Further long-term follow-up is necessary.

Aged↗

PubMed1980

Below-knee bypass for limb salvage. Comparison of autogenous saphenous vein, polytetrafluoroethylene, and composite dacron-autogenous vein grafts.

Autogenous saphenous vein was used preferentially for 92 below-knee bypass procedures (44 femoral-distal popliteal and 48 femoral-distal tibial or peroneal) performed for limb salvage in 87 adult male patients during a 30-month period of study. When a saphenous vein was unavailable or of unsuitable length or diameter, we randomly used expanded polytetrafluoroethylene (PTFE) and composite Dacron-autogenous vein (DV) grafts. With good run-off, all grafts have remained patent. However, with poor run-off, cumulative patency by the life table method decreased to 54% for autogenous saphenous vein and 45% for PTFE, which was not significantly different. All composite DV grafts used with poor run-off became occluded within the first ten months of the study. We continue to recommend use of autogenous saphenous vein for revascularization of the ischemic lower extremity. When a suitable saphenous vein is unavailable, PTFE is a satisfactory alternative graft that is superior to composite DV grafts.

Aged↗

PubMed1981

Femorotibial bypass grafts with sequential technique. Clinical results.

Twenty-three patients (mean age, 71 years) have undergone femorotibial bypass grafting with a sequential side-to-side popliteal anastomosis since 1975, 96% because of threatened limb loss. Twenty-one grafts were of autogenous saphenous vein and two were composites of prosthesis and vein. Ankle-brachial indices increased from 0.40 +/- 0.27 to 0.84 +/- 0.36. Intraoperative flow measurements showed a 40% to 75% augmentation in flow with the sequential anastomosis. Patients who required amputation in the early postoperative period because of graft failure failed to show improvement in ankle indices and did not manifest healing of their ischemic ulcerations. Nineteen of 23 limbs (83%) were salvaged by operation. Follow-up ranged from two to 50 months (mean, 23 months). Graft patency calculated by the life-table method was 74% at one year, 68% at two years, and 62% at four years.

Actuarial Analysis↗

PubMed1982

Transluminal dilation. An alternative?

In a prospective study, 384 peripheral arterial transluminal dilations were evaluated, using clinical and vascular laboratory criteria, and analyzed by the life-table method. The overall cumulative success rate was 58.9 +/- 3.3% (mean +/- SEM) after two years but was higher if the iliac segment was dilated, only one site was dilated, the clinical indication was claudication, the distal vessels were normal, the ankle-brachial BP ratio was more than 0.35, or if the patient was younger than 55 years. The complication rate was 3.9%. If the dilation failed, the symptoms were worse in 8% and the ankle-brachial BP ratio fell in 23%. After successful dilation in patients with normal distal vessels, residual claudication persisted in 34%, and the ankle-brachial BP ratio remained abnormal in 40%. Although the overall success rate of transluminal dilation was lower than for a comparable surgical procedure, dilation does have a role in the management of localized peripheral vascular disease.

Actuarial Analysis↗

PubMed1983

Femoropopliteal and tibioperoneal artery reconstruction using human umbilical vein.

We used 99 human umbilical vein (HUV) grafts for femoropopliteal or tibioperoneal artery reconstruction in 94 patients. Results were calculated according to the life-table method for several categories possibly influencing graft patency. For above-knee v below-knee distal anastomosis, there was no difference in patency or limb-salvage rates at 30 months. Comparison of good and poor runoff situations disclosed similar 30-month graft patency rates, but significantly better limb-salvage rates among patients with good runoff. Primary revascularization fared significantly better than secondary procedures in terms of patency and limb salvage. We found no significant differences between HUV and polytef (polytetrafluoroethylene) for above-knee anastomoses or good runoff situations. However, patency and limb salvage were better for HUV use in below-knee anastomosis and poor runoff situations. The HUV may offer advantages in long-term patency and limb salvage in selected patients.

Aged↗

PubMed1987

Subclavian artery insufficiency. Treatment with axilloaxillary bypass.

Twenty patients underwent axilloaxillary bypass at Tufts-New England Medical Center, Boston, between 1973 and 1983, all for tight stenosis or occlusion of the subclavian artery. Review of records was possible for 19 cases. Symptoms included intermittent claudication and numbness of the upper extremity, as well as dizziness, vertigo, and ataxia due to episodes of vertebrobasilar insufficiency. Dacron, reversed saphenous vein, and polytetrafluoroethylene grafts were inserted, with all but one occupying a subcutaneous tunnel across the sternum. There were no operative deaths, and morbidity was minimal. The median follow-up was 83 months. The early patency rate was 94%, with a cumulative patency rate of 89% at ten years of follow-up, as determined by the life-table method. Our experience supports axilloaxillary bypass as a safe and effective treatment for symptomatic subclavian artery insufficiency.

Adult↗

PubMed1991

Long-term results following surgical management of aortic graft infection.

Between January 1970 and June 1988, a total of 45 patients with aortic prosthetic graft infection underwent removal of the infected aortic prosthesis. In addition, 36 of these patients also underwent revascularization via an extra-anatomic bypass. We analyzed the early and long-term results with respect to survival, limb salvage, freedom from infection, and extra-anatomic graft patency. The 30-day mortality was 24% (11/45), and the amputation rate was 11% (8/73). During a mean follow-up of 36 months (range, 2 to 144 months), 80% (24/30) of the patients remained free of infection and are considered cured. Infection in the extra-anatomic bypass graft was the most common cause of recurrent sepsis and the leading cause of late amputations (four of seven). By life-table methods, 1-year survival was 63% and 5-year survival was 49%. Limb salvage rates at 1 and 5 years were 79% and 66%, respectively. The primary patency rate of extra-anatomic bypass was 43% at 3 years, with the secondary patency rate improved to 65%. These early and late results are in marked contrast to the natural history of untreated aortic graft infection. Nonetheless, a perioperative mortality rate of 24%, a 5-year limb loss rate of 33%, and 3-year graft thrombosis rate of 35% are testimony to the serious nature of aortic graft infection and the need to develop better methods to prevent this complication.

Actuarial Analysis↗

PubMed1993

Popliteal-tibial bypass grafts in the management of limb-threatening ischemia.

OBJECTIVES: To ascertain the cumulative rates of primary graft patency and limb salvage and the frequency of proximal arterial disease progression in patients with autologous saphenous vein bypass grafts that originate from the popliteal artery and whose operative indication was limb-threatening ischemia. DESIGN: Five-year retrospective study with follow-up that ranged from less than 1 month to 60 months. SETTING: Tertiary care center. PATIENTS: Twenty-four threatened limbs in 23 patients were reviewed. Surgical indications included gangrene in 15 limbs (63%), rest pain in seven limbs (29%), and a nonhealing ulcer in two limbs (8%). Patients with previous ipsilateral infrainguinal arterial reconstructive procedures were excluded. Mean patient age was 66 years, and 18 patients 78% had insulin-dependent diabetes mellitus. MAIN OUTCOME MEASURES: Percentages of primary graft patency and limb salvage were determined by the life-table method. Proximal arterial disease progression was assessed via follow-up arteriography or segmental limb pressures. RESULTS: The cumulative rates of primary graft patency and limb salvage at 1, 3, and 5 years were 73%, 59% and 59%, and 87%, 57%, and 57%, respectively. No patient developed proximal arterial disease progression that required intervention during the study period. CONCLUSIONS: The cumulative rates of primary graft patency and limb salvage were essentially the same, which indicated poorly collateralized limbs that are solely dependent on the graft. There did not appear to be a critical progression of proximal arterial disease that would warrant a more proximal graft origin. A short autologous saphenous vein graft that originates from the above-knee or below-knee popliteal artery is a durable bypass.

Aged↗

PubMed1997

Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome.

During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

Adolescent↗

PubMed2001

Comparison of histological grading and large-scale genomic status (DNA ploidy) as prognostic tools in oral dysplasia.

Approximately one in ten oral white patches (leukoplakia) are histologically classified as dysplasia, with a well-documented potential for developing into oral squamous cell carcinoma (OSCC). Histological grading in oral dysplasia has limited prognostic value, whereas large-scale genomic status (DNA ploidy, nuclear DNA content) is an early marker of malignant transformation in several tissues. Biopsies from 196 patients with oral leukoplakia histologically typed as dysplasia were investigated. Inter-observer agreement among four experienced pathologists performing a simplified grading was assessed by Cohen's kappa values. For 150 of the 196 cases, it was also possible to assess large-scale genomic status and compare its prognostic impact with that of histological grading. Disease-free survival was estimated by life-table methods, with a mean follow-up time of 103 months (range 4-165 months). The primary considered end-point was the subsequent occurrence of OSCC. For grading of the total of 196 cases, kappa values ranged from 0.17 to 0.33 when three grading groups (mild, moderate, and severe dysplasia) were considered, and from 0.21 to 0.32 when two groups (low grade and high grade) were considered (p=0.41). For the 150 cases in which large-scale genomic status was also assessed, kappa values for the histological grading ranged from 0.21 to 0.33 for three grading groups and from 0.27 to 0.34 for two grading groups (p=0.47). In survival analysis, histological grading was without significant prognostic value for any of the four observers (p 0.14-0.44), in contrast to DNA ploidy (p=0.001). It is concluded that DNA ploidy in oral dysplasia has a practical prognostic value, unlike histological grading of the same lesions.

Adult↗

PubMed1977

Multiple primary cancers: review of clinical studies from two Missouri hospitals.

A composite review of a series of hospital-based, clinical studies on the prevalence of simultaneous and nonsimultaneous multiple primary cancers, including those in which data were recorded by the life table method for six different series of cancer patients and one "control" series of patients who did not have cancer at first contact is provided. The studies came from Barnes Hospital and the Ellis Fischel State Cancer Hospital (EFSCH) and span the period from 1914 through 1964. The conclusions of the studies support the concept that the presence of one primary cancer neither increases nor decreases the chances for developing additional cancers with the possible exception of a few "target organ" areas. One study of this period showed a nonrandom distribution of patients with multiple primary cancers referred to EFSCH and this observation merits further epidemiologic research.

Adolescent↗