Median Length Of Life Research Articles

Factors affecting the efficacy of gemcitabine and nab-paclitaxel (paclitaxel + albumin) combination in the Russian patient population: results of a multicenter retrospective study

Introduction . The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods . The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results . 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings . The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

FOLFOXIRI in patients with colon cancer and isolated non-resectable liver metastases: phase II prospective non-randomized single-center study

Objective: to assess the frequency of liver resections in patients with metastatic colon cancer and isolated non-resectable liver metastases receiving FOLFOXIRI. Materials and methods. In this single-center non-randomized prospective study, we assessed the frequency of liver resections. According to the statistical hypothesis, the frequency of R0-resections in patients with metastatic colon cancer receiving FOLFOXIRI is between 11 % and 33 % (mean 20 %); to increase it up to 50 % in patients with isolated metastatic lesions in the liver, we had to recruit 20 patients (with β = 0.9 and a = 0.05). We enrolled 20 patients with potentially resectable metastases and 22 patients with non-resectable metastases. The primary endpoint was the frequency of R0 liver resections; secondary endpoints included objective response rate, progression-free survival, overall survival, and tolerability of therapy. Patients receiving targeted therapy (according to the tumor mutation status) were also included in the study.Results. Objective response was observed in 32 out of 42 patients (76 %) (in 17 out of 20 participants (85 %) with potentially resectable metastases), whereas progressive disease was registered in 2 patients (5 %). Radical resection of organs affected by metastasis was performed in 19 out of 42 patients (45 %): 15 out of 20 (75 %) in the group with potentially resectable metastases and 4 out of 22 (18 %) in the group with non-resectable metastasis (р <0.01). At a median follow-up of 11 months (range: 1–32 months), median progression-free survival was 10 months (95 % confidence interval (CI) 8.9–11.1), while median length of life was 34 months (95 % CI 21.3–46.7). Median overall survival was 34 months in patients that had undergone metastasectomy vs 19 months in patients that had no metastasectomy (hazard ratio 0.7; 95 % CI 0.01–0.70; p = 0.02).Conclusions. FOLFOXIRI increased the frequency of metastasectomy in patients with potentially resectable liver metastases from colon cancer, which was associated with a pronounced increase in the length of life.

Metastasectomy in patients with non-resectable metastatic colorectal cancer receiving chemotherapy and anti-EGFR antibodies: a prospective, non-randomized, multicenter, phase II study

Objective: to analyze the frequency of metastasectomy in general population of patients with RAS wild-type metastatic colorectal cancer who received chemotherapy and anti-EGFR monoclonal antibodies Materials and methods . This prospective, non-randomized, multicenter study was designed to evaluate the frequency of resections of organs affected by metastasis. Our statistical hypothesis was that the addition of anti-EGFR antibodies should increase the frequency of metastasectomy from 5% to 15 %. Sample size calculations showed that to obtain a power of 80 % and an alpha level of 0.05 to detect the difference, we would need to recruit 50 patients. The primary endpoint was the frequency of resections of organs affected by metastasis, whereas the secondary endpoints included objective response rate, progression-free survival, and length of live. Tolerability of the therapy was analyzed separately. Results. Eighteen out of50 (36 %) patients achieved objective response; 32 (64 %) patents achieved stable disease and 18 (36 %) patients had disease progression. Radical resection of organs affected by metastasis was performed in 8 out of 50 patients (16 %): 1 individual had lung resection and 7 individuals had liver resection. Among participants with isolated liver lesions, the frequency of metastasectomy was 24 % (6 out of 25 patients). At a median follow-up of 14 months (between 1 and 34 months), median progression-free survival was 8 months (95 % confidence interval 6.2—9.8) and median length of life was 26 months (95 % confidence interval 19.7—32.2). The estimated 2-year overall survival was 83 % in patients who underwent metastasectomy vs. 51 % in those who had no metastasectomy. Conclusions. The addition of anti-EGFR monoclonal antibodies to standard combination chemotherapy (FOLFOX/FOLFIRI) increases the frequency of metastasectomy in patients with non-resectable metastatic colorectal cancer, which results in an increased length of life.

The population-level impact of public-sector antiretroviral therapy rollout on adult mortality in rural Malawi.

BACKGROUNDRecent evidence from health and demographic surveillance sites (HDSS) has shown that increasing access to antiretroviral therapy (ART) is reducing mortality rates in sub-Saharan Africa (SSA). However, due to limited vital statistics registration in many of the countries most affected by the HIV/AIDS epidemic, there is limited evidence of the magnitude of ART’s effect outside of specific HDSS sites. This paper leverages longitudinal household/family roster data from the Malawi Longitudinal Survey of Families and Health (MLSFH) to estimate the effect of ART availability in public clinics on population-level mortality based on a geographically dispersed sample of individuals in rural Malawi.OBJECTIVEWe seek to provide evidence on the population-level magnitude of the ART-associated mortality decline in rural Malawi and confirm that this population is experiencing similar declines in mortality as those seen in HDSS sites.METHODSWe analyze longitudinal household/family-roster data from four waves of the MLSFH to estimate mortality change after the introduction of ART to study areas. We analyze life expectancy using the Kaplan–Meier estimator and examine how the mortality hazard changed over time by individual characteristics with Cox regression.RESULTSIn the four years following rollout of ART, life expectancy at age 15 increased by 3.1 years (95% CI 1.1, 5.1), and median length of life rose by over ten years.CONTRIBUTIONOur observations show that the increased availability of ART resulted in a substantial and sustained reversal of mortality trends in SSA and assuage concerns that the post-ART reversals in mortality are not occurring at the same magnitude outside of specific HDSSs.

Impact of health disorders and culling reasons on functional and biological longevity in Warmblood breeding stallions

The objective of this study was to compare the impact of health disorders and reasons for culling on the functional and biological longevity of warmblood breeding stallions using semi-parametric survival analysis accounting for competing risks. Complete breeding records were collected from 455 warmblood stallions serving between 1975 and 2010 at Marbach State Stud in Germany. The median length of life (18.0years) was twice as long as the median length of service (9.0years). However, both figures increased significantly over the time period examined (e.g., functional longevity increased from 5years in the 1970s to 8years in the 1980s to 12years in the 1990s).Compared to disorders of the musculoskeletal system, hazards for termination of functional life were higher for infectious diseases with a hazard ratio (HR) of 3.5, and for dissatisfaction with performance (HR, 2.0). Hazards were lower for disorders of the respiratory system (HR, 0.78), followed by accidents (HR, 0.58), disorders of the reproductive system (HR, 0.51), sale for non-breeding purposes (HR, 0.40), disorders of the gastrointestinal system (HR, 0.36), unknown reasons (HR, 0.32) and disorders of the cardiovascular system (HR, 0.25). For biological life, the relative importance of these disorders was similar.Factors linked to demand for stallions such as coat colour and several parameters of the stallions’ genetic merit (negative influence) and own performance (positive influence) in dressage and particularly in show-jumping influenced (P<0.05) or tended to influence (P<0.1) functional, but not biological longevity. Furthermore, hazards for both functional and biological life declined with rising stud fees (both HR, 0.99; P<0.0001). A more direct consideration of both functional and biological longevity in breeding programmes might help to further enhance both figures, and therefore welfare of the horses.

Serological prevalence of hepatitis B virus and hepatitis C virus infection in the elderly population

The hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may seriously affect survival rate. The median length of life in developed countries is increasing and the elderly may be considered as an epidemiologically distinct group due to higher whole-life risk of blood-borne viral infections. To determine the seroprevalence of HBV and HCV infections in elderly individuals participating in a Polish nationwide survey - PolSenior. A total of 4979 individuals aged 65 years and older were asked about past or present viral hepatitis, and a blood test was carried out for HBsAg and anti-HCV antibodies in 3826 individuals. The respondents were divided into six age groups of equal size: 65-69, 70-74, 75-79, 80-84, 85-89, and 90+ years. Past or present diagnosis of viral hepatitis was reported by 176 individuals (3.58%) and its prevalence was significantly most common in urban than in rural residents (4.02 vs. 2.92%; P=0.04). In multivariate analysis, only the job category was a significant variable (P=0.01) for the occurrence of viral hepatitis [most frequently in white-collar workers (3.56%) and least frequently in agricultural workers (1.47%)]. The overall prevalence of a positive HBsAg test was 1.12% (n=43) and that of an anti-HCV test was 2.93% (n=112). Only 12 anti-HCV-positive patients (10.7%) were aware of infection. Multivariate analyses did not indicate significant effects of age, sex, alcohol consumption, nutrition, marital or economic status, educational level, and site of residence on the incidence of HBV and HCV infections. HBsAg was associated with higher serum levels of aspartate aminotransferase, and anti-HCV with higher levels of aspartate aminotransferase and alanine aminotransferase. In elderly individuals, the seroprevalence of HBsAg is lower and the seroprevalence of anti-HCV is considerably higher than that in the general Polish population. The former may have been because of increased mortality from HBV-related complications and the latter of increased whole-life risk of infection. Programs for screening of elderly individuals for occult HCV infection should be considered.

Life expectancy

We give simple upper and lower bounds on life expectancy. In a life-table population, if e(0) is the life expectancy at birth, M is the median length of life, and e(M) is the expected remaining life at age M, then (M+e(M))/2≤e(0)≤M+e(M)/2.

Cystic fibrosis mortality trends in France

Background In 1992 France set up a national cystic fibrosis observatory ( Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. Methods The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. Results In 2001–2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994–1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. Conclusions These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.

Estimates of longevity and causes of culling and death in Swedish warmblood and coldblood horses

Data on several different horse populations were analysed and compared regarding length of life and diseases or injuries leading to death or culling. In order to include information for horses still alive, a failure time (survival) analysis was used. The first material included 1847 warmblood horses born between 1968 and 1982, that had participated in the Swedish Riding Horse Quality Test (RHQT) as 4-year-olds. The next two materials included 344 warmblood and 204 coldblood horses owned by the Swedish Cavalry Horse Foundation (CHF), born between 1970 and 1975. The last population consisted of 481 warmblood brood-mares born between 1965 and 1967. According to this study it was important to estimate the median length of life separately for each sex. For warmblood brood-mares and mares that had participated in the RHQT, comparable figures of 18.6 and 18.3 years were found. Close agreement was also found between geldings of the CHF and males that had participated in the RHQT; the estimates were 14.7 and 13.9 years, respectively. There was a positive trend in the median length of life over time for horses that had participated in the RHQT, and the median length-of-life curve increased more steeply for mares than for males. This study showed a longer median length of life for coldblood geldings, 17.6 years, than for the mares, 16.4 years. The most common causes of death of warmblood horses were diseases of the musculoskeletal system (56–57%), respiratory diseases (8–9%), diseases of the digestive system (5–6%) and accidents (3–9%). The primary causes of death of coldblood horses were temperamental disorders (23%), diseases of the musculoskeletal system (14%) and hoof diseases (8%).

Lodewijk and Christiaan Huygens: mean length of life versus probable length of life

In their correspondence of 1669, Huygens brothers introduce the distinction between esperance and apparence, that is to say between mean length of life (or life expectancy) and probable length of life (or median length of life). Unlike Lodewijk, Christiaan adopts a probabilistic approach; he considers more meaningful the probabilities to reach specific ages and the probable length of life than the reste de vie, computed by his brother, which is only a mean.

Long-term prognosis of haemangioblastoma of the CNS: impact of von Hippel-Lindau disease.

The aim was to assess the frequency of von Hippel-Lindau disease (VHL) and the long-term prognosis of VHL and non-VHL patients among 110 consecutive patients with haemangioblastoma (HB) of the CNS treated between 1953 and 1993 at one neurosurgical unit. To reveal VHL manifestations we performed a detailed clinical and radiological examination (neuraxis and abdomen) (61/110), VHL-gene mutation analysis (40/110), and collection of all available clinical, imaging, operative and autopsy data from the hospitals involved. All patients were followed-up with a median of 14 years (excluding 14 operative deaths), and no patient was lost to follow-up. Altogether 49 patients died during the follow-up. In the 14 VHL patients (13%), HB(s) of the CNS were detected at a median age of 33 years, retinal HB(s) at 39 years, and renal cell carcinoma (RCC) at 43 years. The frequency of VHL in patients operated on for HB(s) was 29% before the age of 25 years, 19% between 25 and 45 years, and only 2% after 45 years. HB patients not meeting the VHL criteria had internal organ cysts in 14%. One non-VHL patient (4%) had two adjacent HBs in the same cyst wall. The growth rates of non-VHL and VHL-related HBs were similar as indicated by the median time to recurrence and the proliferation indices (MIB-1). Recurrence of the HB in patients whose primary operation was considered radical developed in four of the 10 VHL patients at a median of 19 years, and in nine of the 74 non-VHL patients at a median of 11 years. The median length of life of all VHL and non-VHL patients was 46 and 63 years, respectively. In VHL, RCC and HBs were equal causes of death.

Temporal Pattern of Food Intake Not a Factor in the Retardation of Aging Processes by Dietary Restriction

Long-term dietary restriction programs which retard aging processes in rodents usually involve meal eating rather than the nibbling pattern of food intake of ad libitum fed rodents. Thus, the possibility arises that the antiaging action may at least in part result from an altered temporal pattern of food intake. This possibility was investigated using male F344 rats maintained on the following dietary regimens: Group A rats fed ad libitum; Group B rats fed 60% the ad libitum intake in a single meal at 1500 h; Group B-2 rats fed 60% of the ad libitum intake in two meals (0700 h and 1500 h). The diurnal pattern of plasma corticosterone concentration differed among the groups as did that of the plasma glucose concentration. The median length of life and age of tenth percentile survivors were similar for Group B and B-2 rats and much greater than those for Group A rats. Both modes of dietary restriction influenced age-associated disease processes in a similar fashion. Thus, although the temporal pattern of food intake influenced circadian rhythms of food-restricted rats, it did not significantly affect the antiaging action.

Life Span, Morphology, and Pathology of Diet-Restricted Germ-Free and Conventional Lobund-Wistar Rats

The effect of germ-free life and dietary restriction (DR) on life span and pathology was investigated in isolator housed germ-free (GF) and conventional (CV) Lobund-Wistar rats fed either ad libitum or restricted to 12 grams per day (70% of adult ad libitum intake) of a natural ingredient diet from weaning. The median length of life of ad libitum CV and GF rats was 31.0 and 33.6 months respectively, while DR increased the median length of life of CV and GF rats to 38.6 and 37.8 months respectively. DR reduced the frequency or postponed the occurrence of diseases which eventually lead to death in the Lobund-Wistar rat. This was especially true of prostate adenocarcinoma, prostatitis, and mammary fibroma. The reduced early food intake and smaller body weight of adult GF rats may be the reason ad libitum fed GF rats live slightly longer than their CV counterparts, but GF life was without additional effect on life span when food intake was restricted.

QUANTITATIVE DESCRIPTION OF THE INFLUENCE OF FLUCTUATING TEMPERATURES ON THE REPRODUCTIVE BIOLOGY AND SURVIVAL OF THE WESTERN CORN ROOTWORM, DIABROTICA VIRGIFERA VIRGIFERA LECONTE (COLEOPTERA: CHRYSOMELIDAE)

AbstractAdult corn rootworm beetles, Diabrotica virgifera virgifera LeConte, were maintained at five fluctuating temperature regimens with daily average temperatures of 16.0, 19.5, 23.0, 26.5, and 30.0°C. The mean number of eggs laid per female was greatest (602) at 26.5°C and least (295) at 16.0°C. The median length of life decreased with increasing temperature from 13.8 weeks at 19.5°C to 7.9 weeks at 30.0°C. Parameters were estimated for nonlinear functions relating age-specific fecundity and age-specific survival to physiological age.

Assessment of Nutritional Components in Prolongation of Life and Health by Diet

Restricting the food intake of rodents extends the median length of life and the maximum life-span. It also retards most age-associated physiologic change and age-associated diseases. Our research indicates that the ability to retard disease processes is not the major reason for the extension of life-span or for the retardation of age change in most physiologic systems. Rather, it appears that most of the actions of food restriction are due to its ability to slow the primary aging processes. We found this action to relate to the restriction of calories rather than specific nutrients (e.g., protein or fat or minerals). Our findings point to the reduction in caloric intake per rat rather than per gram lean body mass as the basis of the retardation of aging processes by food restriction. The challenge is to learn how caloric intake per rat is coupled to the aging processes. We are currently focusing on the possibility that neural and endocrine mechanisms are involved. Our preliminary findings point to the likelihood of an involvement of the insulin-glucose system.

Influence of the restriction of individual dietary components on longevity and age-related disease of Fischer rats: the fat component and the mineral component.

The influence of restricting either the fat or the mineral component of the diet to the same extent as they are restricted in the life-prolonging, food-restriction paradigm but without restricting calories was studied in regard to longevity and age-related pathologic lesions of barrier-maintained male Fischer 344 rats. Neither the restriction of fat nor the restriction of mineral influenced the median length of life or maximum life span as indicated by the age of the 10th percentile survivors. Restricting the dietary fat did retard the development of chronic nephropathy and associated lesions, but it also increased the prevalence of lymphoma and leukemia. The development of chronic nephropathy was not significantly affected by restricting the mineral component of the diet.

The influence of dietary protein source on longevity and age-related disease processes of Fischer rats.

The influence of replacing dietary casein with soy protein on longevity and age-related pathologic lesions of male Fischer 344 rats was investigated. Caloric intake and body weights were similar for rats on the two diets. Rats on the soy protein-containing diet had a median length of life of 844 days compared to 730 days for those on the casein-containing diet (p less than .002), and the ages of the 10th percentile survivors were 937 and 857 days, respectively (p less than .02). The progression of chronic nephropathy was markedly retarded by replacing casein with soy protein. Only 7% of the rats dying spontaneously on the soy protein-containing diet exhibited end-stage chronic nephropathy compared to 41% of the rats on the casein-containing diet. Clearly, the soy protein-containing diet enables ad libitum fed male Fischer 344 rats to be used as a model for aging research without the occurrence of renal failure as a major confounding problem.

Maintenance of glucagon-promoted lipolysis in adipocytes by food restriction.

Life-prolonging food restriction is known to delay physiological changes that occur during senescence. The aim of the present study was to learn if this nutritional manipulation also can influence changes that occur during the developmental phase of life. Male, specific pathogen-free Fischer 344 rats were fed ad libitum (group A) or 60% of the ad libitum intake (group R) beginning at 6 weeks of age. The group R rats had a markedly increased median length of life. Starting at 6 months of age, rats were periodically killed, and free adipocytes were prepared from epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the promotion of lipolysis by glucagon. At 6 months of age and all older ages, adipocytes from group A rats were not responsive to the lipolytic action of glucagon; this agrees with earlier studies showing a marked loss in responsiveness to glucagon between 4-15 weeks of age. However, adipocytes from group R rats were quite responsive to glucagon at 6 and 12 months of age. Although after 12 months of age there was a loss in responsiveness to glucagon, this response remained significant through 36 months of age in the group R rats. Thus, life-prolonging food restriction delays not only functional changes that take place late in life (senescent changes) but also those occurring during the developmental period of life. The value of these findings as a model for experimental gerontology is discussed.

Nutrition-aging influence of catecholamine-promoted lipolysis

Male SPF Fischer 344 rats were fed ad lib. (group A) or 60% ad lib. intake (group R) from 6 wk of age. The group R rats had a markedly increased median length of life. Starting at 6 mo of age, rats were periodically killed and free adipocytes prepared from the epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the effects of age on the promotion of lipolysis by catecholamines. At 6 mo of age, the response of the adipocytes from group A and group R rats was similar when the data are expressed as μmole glycerol released/10 6 adipocytes. With increasing age, however, this lipolytic response to catecholamines of group A rats markedly declined. The catecholamine-stimulated lipolysis/10 6 adipocytes from group R rats changed little between 6 and 18 mo of age, and the decline noted after 18 mo of age was less marked than that occurring in adipocytes from group A rats. The data based on rates of lipolysis/10 6 adipocytes indicate that it is the lifelong nutritional history of a rat population that determines the age-related changes in responsiveness of adipocytes to catecholamines. However, if the data are expressed per sq mm of adipocyte surface, a somewhat different picture emerges. These data are presented and their relevance is discussed.

Food restriction as a modulator of age-related changes in serum lipids.

Fischer 344 male rats were either fed ad libitum or 60% of the ad libitum intake. The restriction of food intake markedly increased the median length of life. Postabsorptive serum cholesterol and phospholipid concentrations increase in the ad libitum-fed rats with increasing age. Life-prolonging food restriction does not influence the serum levels of these lipids in young rats but delays the age-related increase in concentrations. Postabsorptive serum free fatty acid (FFA) concentrations decrease with advancing age in ad libitum-fed rats. Life-prolonging food restriction, while not affecting the serum FFA levels in young rats, delays and possibly partially prevents the age-related decrease in concentration. Food restriction lowers postabsorptive serum triglyceride levels at all ages studied. The data on serum cholesterol, phospholipids, and FFA provide further evidence that food restriction delays age-related changes in the physiological systems of rats. This delay of physiological decline may well retard the occurrence of age-related disease processes, thus prolonging life.