Economic evaluation of hemodialysis: implications for technology assessment in Greece

OBJECTIVES: Hemodialysis is a well-established treatment for 74 percent of end-stage renal disease (ESRD) patients in Greece. The purpose of this study is to provide an estimate of the direct cost of dialysis in a public hospital setting and an estimate of the loss of production for ESRD patients. The results will be useful for public health facility planning purposes. METHODS: A socioeconomic prevalence-based analysis was performed using micro-economic evaluation of health-care resources consumed to provide hemodialysis for ESRD patients in 2000. Lost productivity costs due to illness were estimated for the patient and family using the human capital approach and the friction method. Indirect morbidity costs due to absence from work and long-term were estimated, as well as mortality costs. Mean gross income was used for both patient and family. RESULTS: Total health-sector cost for hemodialysis in Greece exceeds 171 million Euros, or 182 Euros per session and 229 Euros per inpatient day. There were 2,046 years lost due to mortality, and the potential productivity cost was estimated at 9.9 million Euros, according to the human capital approach, and 303.000 Euros, according to the friction method. Total morbidity cost due to absence from work and early retirement was estimated at more than 273 million Euros, according to the human capital approach, and 12.5 Euros, according to the friction method. CONCLUSIONS: Providing hemodialysis care for 0.05 percent of the population suffering from ESRD absorbs approximately 2 percent of total health expenditure in Greece. In addition to the cost for the National Health System, production loss due to mortality and morbidity from the disease are also considerable. Promoting alternative technologies such as organ transplantation and home dialysis as well as improving hemodialysis efficiency through satellite units are strategies that may prove more cost-effective and psychologically advantageous for the patients.     

血液透析患者新发房颤的临床分析

目的：房颤是否增加维持性透析患者死亡率尚无定论。我们回顾分析了维持性血液透析患者的房颤发生率，并对其临床相关因素进行了探讨。方法：观察本中心2005年1月到2007年6月维持性血液透析超过3个月的患者，记录他们的年龄，透析方式，房颤发生情况及血红蛋白维持水平。结果：168例患者中，12例新发房颤，发生率为7．14％，年龄大于55岁的患者共90例，房颤发生率为11．45％，显著高于年龄小于55岁的患者。透析龄大于4年的房颤的发生率为11．11％，房颤患者和非房颤患者血红蛋白水平无明显差异。非房颤患者中有25例发生心梗或脑梗，发生率为15．15％，而房颤患者中发生两例脑梗，发生率为16．67％。结论：1．透析患者的房颤发生率高于普通人群；2．随着年龄的增加房颤的发病率增加，55岁以上的房颤发病率明显升高；3．随着透析年限的增加房颤的发病率也增加，血液透析4年以上房颤的发病率明显升高。     

Provision of home dialysis by freestanding renal dialysis facilities

This article explores home dialysis provision among freestanding renal facilities by examining whether they provide continuous ambulatory peritoneal dialysis (CAPD), continuous cycling peritoneal dialysis (CCPD), and home hemodialysis. These modalities require fewer visits to a dialysis center, which may be beneficial for patients living long distances from facilities. A negative association was found between the number of facilities per square mile and the probability of provision of the home modalities. Secondly, facilities with a higher percent of black patients were less likely to provide the home modalities. Thirdly, facilities with larger numbers of patients were more likely to provide the home modalities.     

The effects of megestrol acetate on nutritional parameters in a dialysis population.

OBJECTIVE: To examine the effect of megestrol acetate on nutritional parameters in a hemodialysis population. DESIGN: Prospective case studies of hemodialysis patients. SETTING: A freestanding, nonprofit, hemodialysis unit. SUBJECTS: Seventeen patients were studied. They were included regardless of gender, age, or cause of renal disease. They had to be on dialysis for at least 2 months, had a serum albumin <3.5 g/dL for these 2 months, and had to be at high nutritional risk. There were 8 women and 9 men. Ages were 44 to 87 years. Eight were diabetics, and 9 were nondiabetics. INTERVENTIONS: Megestrol acetate 400 mg orally twice daily was prescribed, and patients were studied for 6 months. OUTCOME MEASURES: Pre-evaluation and postevaluation were performed by patient questionnaire, Subjective Global Assessment (SGA), dry weight, and anthropometric measurements. Monthly laboratory monitoring included albumin, prealbumin, blood urea nitrogen (BUN), cholesterol, triglycerides, carbon dioxide, platelets, hematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase, and glucose. Glycohemoglobin and hemoglobin A1c were monitored in diabetic patients. RESULTS: Three patients were able to take megestrol acetate for 5 to 6 months. They reported improved appetite and showed an increase in dry weight. The annualized mortality rate was about 59%. Side effects included diarrhea, confusion, hyperglycemia, headaches, dizziness, and elevated LDH. CONCLUSION: Megestrol acetate may help stimulate appetite in the hemodialysis patient, but it is risky and must be monitored closely. Eight hundred milligrams per day is probably too large a dose for the end-stage renal disease (ESRD) patient.     

Hemodialysis for end-stage renal disease: a cost-effectiveness analysis of treatment-options

BACKGROUND: During 2001, over 32,000 patients in the United Kingdom received renal replacement therapy (RRT). Approximately half had a functioning transplant, with the remainder receiving dialysis therapy. The main form of dialysis is hemodialysis (HD), which is provided to 37.1 percent of the RRT population. HD is provided in three main settings: hospital (24.5 percent), satellite (10.9 percent), or home (1.7 percent). The objective of this study is to explore the cost-effectiveness of these different modalities. METHODS: By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the three different modalities. The model included direct health service costs and quality-adjusted life years (QALYs). Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Satellite HD has lower costs 46,000 pounds sterling and 62,050 pounds sterling at 5 and 10 years than home HD 47,660 pounds sterling and 63,540 pounds sterling. The total effectiveness of home HD was slightly greater than for satellite HD, so the incremental cost per QALY of home versus satellite HD was modest at 6,665 pounds sterling at 5 years and 3,943 pounds sterling at 10 years. Both modalities dominated hospital HD. CONCLUSIONS: Results from the study reveal that satellite HD was less costly than home HD, and home HD was less costly than hospital HD. The lack of robust data on the effectiveness and new dialysis equipment, which were not included in this review, throws some caution on these results. Nonetheless, the results are supportive of a shift from hospital HD to satellite and home HD.     

Outbreak of hemodialysis vascular access site infections related to malfunctioning permanent tunneled catheters: making the case for active infection surveillance.

OBJECTIVE: To describe an outbreak of infections with permanent cuffed hemodialysis catheters recognized through ongoing surveillance and related to a specific malfunctioning permanent catheter. DESIGN: The outbreak was suspected from the results of prospective infection surveillance and confirmed by a retrospective cohort study using medical records for patients receiving dialysis between April 1, 1999, and March 31, 2000. SETTING: Integrated network of six outpatient hemodialysis facilities in southern Idaho and eastern Oregon. PATIENTS: Outpatients receiving long-term hemodialysis. RESULTS: During the 18 months prior to the outbreak, the overall infection rate was 4.1 infections per 1,000 dialysis sessions with a catheter rate of 8.9 per 1,000 dialysis sessions. During the 7 months of the outbreak, the overall rate increased to 5.8 per 1,000 dialysis sessions, whereas the catheter rate increased to 18.1 per 1,000 dialysis sessions. Reports of malfunctioning "Brand A" catheters prompted discontinuation of their placement. A manufacturer recall occurred in April 2000. During the 14 months after the outbreak, the overall infection rate decreased to 3.3 per 1,000 dialysis sessions and the catheter rate to 10.8 per 1,000 dialysis sessions. A 12-month retrospective cohort study recognized 96 patients with an identifiable catheter brand and 48 infections. Of these, 27 (56%) occurred in patients with Brand A catheters. The relative risk for infection when compared with other catheter brands was 1.96 (95% confidence interval, 1.32 to 2.92; P < .001). CONCLUSIONS: Ongoing infection surveillance in hemodialysis facilities can identify specific device-related outbreaks of infections and promote interventions to reduce infectious complications and promote patient safety. Surveillance for vascular access site infections is recommended as a routine activity in hemodialysis facilities.     

Epidemiology of end stage renal disease and implications for public policy

In 1972 the Congress extended Medicare coverage to all persons under age 65 suffering from end stage renal disease (ESRD). The intent of this law (PL 92-603, the Social Security Amendments of 1972) was to allow all Americans access to an emerging and very expensive technology, regardless of their ability to pay. The legislation had an immediate and dramatic impact on the population receiving dialysis. Prior to the passage of the legislation the dialysis population was white, educated, young, married, employed, and male. Within 4 years after implementation of the law, the dialysis population was more than one-third nonwhite, less well educated, significantly older, and about half female--making it more representative of the population as a whole. During consideration of this legislation the dialysis population was expected to increase from 5,000 to 7,000 patients and cost $135 million in the first year. Actually, in the first year of the program, there were 10,300 patients and the cost was $241 million. Today, while patients with ESRD represent only 0.25 percent of Medicare beneficiaries, they consume approximately 10 percent of the Medicare Part B budget. The humanitarian goals of the legislation have been met, but the costs of this program continue to rise as enrollment continues to grow. It is hoped that, through research and reimbursement policies, the per capita costs can be controlled and total costs can be reduced by shifts in treatment patterns and improvement in successful transplantation rates. There will, however, continue to be demands on our health care financing system to include reimbursement for new therapeutic modalities such as artificial hearts and heart and liver transplants.The lesson from the ESRD Program is that sound decisions require accurate epidemiologic data and cost projections.It is a challenge not easily met.     

糖尿病肾病患者使用血液透析机透析的时机观察

目的:探究糖尿病肾病患者使用血液透析机透析的时机。方法:回顾性分析本院2012年1月~2017年12月收治的42例行血液透析的糖尿病肾病患者的临床资料。其中,有24例患者在血肌酐达到707μmol/L时开始行长期血液透析(正常组),剩余18例患者透析前患者血肌酐在224~675uomL/L间,均因不同病情提前开始进行血液透析治疗(提前组)。结果:正常组中有13例患者死亡,剩余11例患者均已出现程度不一的血管病变情况,且均须通过血液透析机行长期透析。提前组中有2例死亡,4例须每周行2次长期透析,2例须每7~10d内行1次透析,有1例患者在出院1年后每周行1次血液透析,1例患者行肾移植,8例患者未再行透析治疗。结论:提前进行血液透析能够减缓糖尿病肾病进展至终末期肾功能衰竭的速度,并有效延长透析间隔时间,降低并发症发生率。     

Survey of home nutritional support patients

Patients receiving home parenteral nutritional services from a major corporate provider were surveyed using a written questionnaire. The survey questioned the patients about use of home parenteral nutritional services and the quality of life while receiving home parenteral therapy. Patient satisfaction with home nutritional support services, and the impact home therapy has on patient medical, financial and psychosocial status were examined. Life satisfaction measures were compared with that of end stage renal disease patients and the overall United States population. Of the 1140 patients sent the written questionnaire, 347 (30.4%) returned the survey. Half the patients had been placed on home parenteral nutrition services because of short bowel syndrome. The mean length of time respondents had been receiving home parenteral nutrition services was 35 months, reporting approximately one hospitalization per year due to complications of their home parenteral nutrition. Blood infection with catheter as focus was most frequently reported as being responsible for hospitalization. The number of hospitalizations due to complications of home parenteral nutrition therapy was positively correlated with length of time on the program. Overall, respondents were satisfied with their home nutrition services, but were less satisfied with life as a whole when compared to the overall United States population and to end stage renal disease patients.     

Value of an Integrated Home Dialysis Model in the United Kingdom: A Cost-Effectiveness Analysis

ObjectivesThis study aimed to determine the lifetime cost-effectiveness of increasing home hemodialysis as a treatment option for patients experiencing peritoneal dialysis technique failure compared with the current standard of care.MethodsA Markov model was developed to assess the lifetime costs, quality-adjusted life-years, and cost-effectiveness of increasing the usage an integrated home dialysis model compared with the current patient pathways in the United Kingdom. A secondary analysis was conducted including only the cost difference in treatments, minimizing the impact of the high cost of dialysis during life-years gained. Sensitivity and scenario analyses were performed, including analyses from a societal rather than a National Health Service perspective.ResultsThe base-case probabilistic analysis was associated with incremental costs of £3413 and a quality-adjusted life-year of 0.09, resulting in an incremental cost-effectiveness ratio of £36 341. The secondary analysis found the integrated home dialysis model to be dominant. Conclusions on cost-effectiveness did not change under the societal perspective in either analysis.ConclusionsThe base-case analysis found that an integrated home dialysis model compared with current patient pathways is likely not cost-effective. These results were primarily driven by the high baseline costs of dialysis during life-years gained by patients receiving home hemodialysis. When excluding baseline dialysis-related treatment costs, the integrated home dialysis model was dominant. New strategies in kidney care patient pathway management should be explored because, under the assumption that dialysis should be funded, the results provide cost-effectiveness evidence for an integrated home dialysis model.     

The effect of dialysis chains on mortality among patients receiving hemodialysis

Objective. To examine the association between dialysis facility chain affiliation and patient mortality. Study Setting. Medicare dialysis population. Study Design. Data from the United States Renal Data System (USRDS) were used to identify 3,601 free‐standing dialysis facilities and 34,914 Medicare patients' incidence to end‐stage renal disease (ESRD) in 2004. Mixed‐effect regression models were used to estimate patient mortality by dialysis facility chain and profit status during the 2‐year follow‐up. Data Collection. USRDS data were matched with facility, cost, and census data. Principle Findings. Of the five largest dialysis chains, the lowest mortality risk was observed among patients dialyzed at nonprofit (NP) Chain 5 facilities. Compared with Chain 5, hazard ratios were 19 percent higher (95 percent CI 1.06–1.34) and 24 percent higher (95 percent CI 1.10–1.40) for patients dialyzed at for‐profit (FP) Chain 1 and Chain 2 facilities, respectively. In addition, patients at FP facilities had a 13 percent higher risk of mortality than those in NP facilities (95 percent CI 1.06–1.22). Conclusions. Large chain affiliation is an independent risk factor for ESRD mortality in the United States. Given the movement toward further consolidation of large FP chains, reasons behind the increase in mortality require scrutiny.     

维持性血液透析患者庚型肝炎病毒感染的研究

目的 了解血液透析患者庚型肝炎病毒(HGV)感染情况，探讨其危险因素。方法 采用酶联免疫法(ELISA)和逆转录—套式PCR法分别检测44例血透患者的抗—HGV抗体和HGVRNA。结果 血透患者HGV感染率为13．6％，HGV阳性组与阴性组相比输血次数较多、透析时间较长，但差异无显著性；而单独HGV阳性组与全阴性组相比透析时间明显延长，HGV感染与年龄、HBV感染、HCV感染及肝功能损害无显著相关。结论 血透患者HGV感染率明显高于普通人群，严格消毒措施、预防交叉感染、减少输血、血源中HGV筛查，对减少透析中庚型肝炎病毒感染至关重要。     

优化健康教育对老年病人血液透析充分性的影响

目的 通过研究优化健康教育对老年血液透析病人的透析效果,评估优化健康教育对透析效果的影响,为改进优质护理提供依据.方法 以实验室数据中的尿素清除指数、白蛋白、血红蛋白、钙磷乘积为指标,对我科52例老年病人透析充分性进行调查,并在实施优化健康教育6个月后再进行调查,对两者数据进行比较.结果 优化老年患者健康教育6个月后,老年透析患者的四项透析充分性指标与实施前相比均有显著差异（P＜0.05）.结论 优化老年患者健康教育有助于提高血液透析充分性,为提高老年透析患者的生活质量提供保证.     

International Study of Health Care Organization and Financing for end-stage renal disease in France

The major features of ESRD management in France include the predominance of hemodialysis and the resulting competition for dialysis stations. In 2003, the prevalence of ESRD in France was 0.087%. Of the 52,000 ESRD patients, 30,882 were receiving dialysis and 21,233 had functioning renal transplants. The annual expenditure per ESRD patient in 2003 was estimated at €40,975. Autodialysis, at €49,133 per patient per year, was much less expensive than dialyzing in-center at either a public or private facility (€111,006 and €75,125, respectively). Transplant activity in France has rapidly increased in recent years, reaching 22 donors per million population in 2005.      

Reexploring Differences among For-Profit and Nonprofit Dialysis Providers

Objective. To determine whether profit status is associated with differences in hospital days per patient, an outcome that may also be influenced by provider financial goals. Data Sources. United States Renal Data System Standard Analysis Files and Centers for Medicare and Medicaid Services cost reports. Design. We compared the number of hospital days per patient per year across for‐profit and nonprofit dialysis facilities during 2003. To address possible referral bias in the assignment of patients to dialysis facilities, we used an instrumental variable regression method and adjusted for selected patient‐specific factors, facility characteristics such as size and chain affiliation, as well as metrics of market competition. Data Extraction Methods. All patients who received in‐center hemodialysis at any time in 2003 and for whom Medicare was the primary payer were included (N=170,130; roughly two‐thirds of the U.S. hemodialysis population). Patients dialyzed at hospital‐based facilities and patients with no dialysis facilities within 30 miles of their residence were excluded. Results. Overall, adjusted hospital days per patient were 17±5 percent lower in nonprofit facilities. The difference between nonprofit and for‐profit facilities persisted with the correction for referral bias. There was no association between hospital days per patient per year and chain affiliation, but larger facilities had inferior outcomes (facilities with 73 or more patients had a 14±1.7 percent increase in hospital days relative to facilities with 35 or fewer patients). Differences in outcomes among for‐profit and nonprofit facilities translated to 1,600 patient‐years in hospital that could be averted each year if the hospital utilization rates in for‐profit facilities were to decrease to the level of their nonprofit counterparts. Conclusions. Hospital days per patient‐year were statistically and clinically significantly lower among nonprofit dialysis providers. These findings suggest that the indirect incentives in Medicare's current payment system may provide insufficient incentive for for‐profit providers to achieve optimal patient outcomes.     

Dialysis modality selection among patients attending freestanding dialysis facilities

Persons with end stage renal disease (ESRD) are eligible to receive dialysis services under the Medicare program. An individual-level analysis was performed to determine the factors associated with the modality selected by patients; namely in-center hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), continuous cycling peritoneal dialysis (CCPD), and home hemodialysis. Logistic regression equations were estimated using program data for 73,448 ESRD Medicare patients attending freestanding dialysis facilities. The results showed that CAPD, CCPD, and home hemodialysis were more likely to be selected by patients who were younger, had non-systemic precipitating causes of ESRD, had a shorter duration of ESRD, attended larger facilities, and were not ethnic minorities. There is no consistent evidence demonstrating the superiority of particular modalities. The policy goal should be to enable beneficiaries to use the modality for which they are best suited, which requires that the range of modalities be available to all ESRD beneficiaries.     

Active Management of Patients with Chronic Renal Insufficiency

Introduction

Suboptimal management of patients with chronic renal insufficiency (CRI) is thought to contribute to the high morbidity and early mortality seen after the onset of end-stage renal disease (ESRD), and may therefore impact on healthcare costs associated with patients with ESRD. The objective of this study was to investigate the effects of pre-dialysis patient care on hospital days during the 6 months after hemodialysis initiation.

Study Design

Data were obtained from Group Health Cooperative in Seattle, Washington, USA, a staff model health management organization with an established, active, CRI management program, and were analyzed retrospectively. Patients who started long-term hemodialysis between 1 January 1997 and 31 January 2000, and who were referred to the Group Health Cooperative CRI management program, were included in the study.

Methods

Demographic and baseline clinical characteristics, details of interventions received by patients prior to dialysis, and hemoglobin (Hb) levels during the 6 months prior to the onset of ESRD were recorded. The numbers of days that each patient spent in hospital during the baseline (1 year to 6 months pre-dialysis), pre-dialysis (180 days pre-dialysis), and post-dialysis initiation (180 days following dialysis initiation) periods were recorded. Hospital days during the post-dialysis initiation period were associated with patient characteristics and pre-dialysis interventions received, and were compared with national data from the US Renal Data System (USRDS).

Results

When calculated similarly to data from the USRDS, the mean number of hospital days for patients in this study was lower than that for the national hemodialysis population (9.4 vs 13.9 days). Temporary vascular access and inadequate nephrology visits prior to dialysis were the key factors increasing the risk of a greater number of hospital days. The use of a catheter for initial dialysis significantly increased patients’ risk of hospital days compared with the use of a fistula or graft (median 4 vs 2 days; odds ratio [OR] 2.5); lack of pre-dialysis nephrology visits had a similar effect. Patients’ Hb levels prior to dialysis were also important: a clinically significant decrease in Hb levels (≥1 g/dL), or a decrease resulting in Hb levels <10 g/dL at dialysis initiation, increased hospital days (median 2 vs 3 days; OR 2.0).

Conclusion

Early, active management of patients with CRI can reduce hospital days and associated costs in the early months after hemodialysis initiation.

     

Delayed nephrologist referral and inadequate vascular access in patients with advanced chronic kidney failure

We sought to determine whether late referral to a nephrologist in patients with chronic renal failure influences the adequacy of vascular access for hemodialysis. We analyzed data describing all health care encounters for all Medicare and Medicaid patients with end-stage renal failure in New Jersey between January 1991 and June 1996. Patients were required to have been diagnosed with renal disease at least 1 year prior to onset of hemodialysis. In the resulting cohort of 2,398 incident hemodialysis patients, 35% had their first nephrologist consultation < or =90 days prior to initiation of dialysis. After controlling for demographic characteristics, socio-economic status and underlying renal disease, we found that patients who were referred to a nephrologist >90 days prior to onset of hemodialysis were 38% more likely to have undergone predialysis vascular access surgery than those who were referred to a nephrologist < or =90 days before dialysis [OR: 1.38; 95% CI (1.15; 1.64)]. Similarly, patients referred late were 42% more likely to require central venous access for hemodialysis compared to those seen by a nephrologist early [OR: 1.42; 95% CI (1.17; 1.71)]. Inadequate development of vascular access for renal replacement therapy in patients with late nephrologist referral unnecessarily contributes to the burden of disease experienced by this vulnerable patient population.     

25 years of kidney replacement treatment at a general hospital

Between February 1963 and January 1988, 174 patients were treated for acute and 307 for chronic renal failure by dialysis in the St. Joseph Hospital Eindhoven, a general hospital. Sixty-two per cent of the patients treated for acute renal failure had tubular necrosis as a cause. In the patients treated for end-stage renal disease the median age of the dialysis population increased from 37 to 62 years. Vascular renal disease and diabetes mellitus were more frequent during the last ten years. Because of the inflow of older people, the outflow by death increased strongly, while the outflow by transplantation remained stable during the last 15 years. Due to an active transplantation policy together with haemodialysis at home and CAPD, 66% of the total now living patient population could be discharged from the dialysis department. Infection and cardiovascular accidents were the major causes of morbidity and mortality among the dialysis and transplant patients. Overall survival curves of all treated patients showed a 5-year survival of 60% and a 10-year survival of 42%.     

Systematic review of the effectiveness of home versus hospital or satellite unit hemodialysis for people with end-stage renal failure

BACKGROUND: Home hemodialysis offers potential advantages over hospital hemodialysis, including the opportunity for more frequent and/or longer dialysis sessions. Expanding home hemodialysis services may help cope with the increasing numbers of people requiring hemodialysis. METHODS: We sought comparative studies or systematic reviews of home versus hospital/satellite unit hemodialysis for people with end-stage renal failure (ESRF). Outcomes included quality of life and survival. We searched MEDLINE, EMBASE, HealthSTAR, CINAHL, PREMEDLINE, and BIOSIS. Two reviewers independently extracted data and assessed the quality of the studies included. RESULTS: Twenty-seven studies of variable quality were included. People on home hemodialysis generally experienced a better quality of life and lived longer than those on hospital hemodialysis. Their partners, however, found home hemodialysis more stressful. Four studies using a Cox proportional hazards model to compare home with hospital hemodialysis reported a lower mortality risk for home hemodialysis. Of two studies using a Cox model to compare home with satellite unit hemodialysis, one reported a similar mortality risk, whereas the other reported a lower mortality risk for home hemodialysis. CONCLUSIONS: Home hemodialysis was generally associated with better outcomes than hospital hemodialysis and (more modestly so) satellite unit hemodialysis, in terms of quality of life, survival, and other measures of effectiveness. People on home hemodialysis, however, are a highly selected group. Home hemodialysis also provides the opportunity for more frequent and/or longer dialysis sessions than would otherwise be possible. It is difficult to disentangle the true effects of home hemodialysis from such influencing factors.