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R I Griffiths

Publications and source records attributed to R I Griffiths.

At least 37 records · Page 2Linked to original sources
PubMed1995

The clinical-economic trial: promise, problems, and challenges.

The clinical-economic trial is a study design that is appearing with greater frequency in medical and public health literature. Some experienced investigators view these trials with skepticism; to policy makers they represent a promising step in the control of rising health care costs. The success of clinical-economic trials in meeting the important goal of more rational and efficient use of health care resources will depend on the strengths and limitations of the research method. As part of a report to the Office of Technology Assessment of the U.S. Congress on new health care assessment techniques, we describe the reasons why economic data collection and analysis are being considered in clinical trials, identify and discuss various designs and methods for gathering economic trial data, and evaluate the strengths and limitations of different methods for providing sound data for decision making on appropriate use of health care interventions. Because of the potential significance and increasing visibility of such research, experts in research methods should give more attention to methodological research for clinical-economic trials. Future efforts should be directed at comparing different techniques for collecting data, examining the incremental value of precision in economic measurements and ensuring appropriate interpretation of data from clinical-economic trials.

Clinical Trials as Topic↗
PubMed1994

Metabolic development of the sheep diaphragm during fetal and newborn life.

Several parameters indicative of whole muscle aerobic and anaerobic metabolism were compared in heart, diaphragm and two locomotory muscles of sheep (Ovis aries) ranging from 90 days gestation to adult animals. Aerobic metabolism was assessed from myoglobin content, anaerobic metabolism from the pH buffering capacity and the balance between the two from the properties of the lactate dehydrogenase isozymes. We expected the diaphragm and heart, as the two vital pumps of the body, to have substantial aerobic capacity at birth. For the left ventricular myocardium this appears to be true, with the myoglobin level at birth averaging 69% of the adult value. However, the diaphragm had only 15% of the adult myoglobin level, a level similar to that in vastus lateralis and medial gastrocnemius muscles. In the first 18 days postnatally, myoglobin levels in the diaphragm did not change. Anaerobic capacity, as indicated by pH buffering capacity, increased in all four muscles during fetal life, reaching from 69-96% of adult values on day 1 after birth. A rapid increase in pH buffering capacity occurred in all four muscles in the first 6 days postnatally suggesting that anaerobic glycolysis is important to the newborn. We conclude that the work done by the fetal heart leads to the development of a high aerobic capacity by birth, but the activity of the fetal diaphragm does not have this effect.

Aerobiosis↗
PubMed1994

The relationship of provider organizational status and erythropoietin dosing in end stage renal disease patients.

Controversy exists as to whether provider organizational characteristics such as profit status and setting are associated with the content of medical care or efficiency with which care is rendered. Following FDA approval of human recombinant erythropoietin (EPO) for use in clinical practice, Medicare approved coverage for beneficiaries in its end stage renal disease program and established a fixed payment per dose. Because cost of EPO administration varied positively with dose, providers could realize larger profit with prescription of smaller doses. We used Medicare claims data to assess EPO use by renal dialysis providers one year after FDA approval (June 1990) as a function of provider ownership (for-profit, not-for-profit, government agency) and setting (hospital-based, free-standing). Mean dose of EPO was 236 units greater (P = 0.0001) for not-for-profit freestanding facilities, 593 units greater (P = 0.0001) for government facilities, and 555 units greater for not-for-profit hospitals (P = 0.0001) than among for-profit freestanding providers. With fixed payment per dose of EPO, for-profit, freestanding providers prescribed EPO more often and administered smaller doses than not-for-profit or government providers, behavior that is consistent with profit maximization.

Ambulatory Care Facilities↗
PubMed1994

Effect of recombinant erythropoietin on hospital admissions, readmissions, length of stay, and costs of dialysis patients.

To examine the effects of recombinant human erythropoietin (rHuEPO) on hospital utilization, hospital costs, and Medicare reimbursements for hospital care, a longitudinal, matched cohort study was conducted using Medicare claims data of 23,806 Medicare-eligible, dialysis patients who received rHuEPO, did not have a transplant, and were alive for 18 mo or longer and 22,720 controls matched on age, sex, race, cause of ESRD, and dialysis modality. The relative odds (rHuEPO versus control) of admission for all causes and for specific causes over 9 mo, adjusted for admission in the prior 9 mo and the per patient change in total admissions, inpatient days, hospital costs, and Medicare hospital payments between the prior 9-mo period and the subsequent 9-mo period was examined. The adjusted relative odds (95% confidence interval) of admission (rHuEPO versus control) was: higher and statistically significant for all causes, 1.08 (1.03 to 1.14); seizure, 1.52 (1.28 to 1.75); vascular access revision, 1.11 (1.06 to 1.17), and heart failure, 1.17 (1.09 to 1.26); higher but not statistically significant for angina, 1.09 (0.99 to 1.20) and stroke, 1.08 (0.86 to 1.31); and lower but not statistically significant for myocardial infarction, 0.91 (0.72 to 1.10); peripheral vascular disease, 0.81 (0.60 to 1.02); anemia, 0.86 (0.56 to 1.17); and depression, 0.89 (0.37 to 1.40). The mean change per 1,000 patients in admissions was less by 38 (P = 0.03) because of fewer readmissions, and in days was 1,309 less (P < 0.001), for patients treated with rHuEPO versus controls. The mean change per patient in hospital costs was $371 less and was statistically significant (P = 0.03) and in Medicare hospital payments was $132 less but was not statistically significant (P = 0.43) for patients treated with rHuEPO versus controls. rHuEPO was associated with an increase in the probability of hospital admission (particularly admissions potentially related to adverse effects) but a decrease in readmissions, overall admissions, hospital days, and cost to hospitals in this cohort of patients surviving for 18 mo. Although not realized short term, Medicare savings from potential rHuEPO-related reductions in hospital care may be long term through future adjustments in diagnosis-related group-based hospital payment.

Adult↗
PubMed1994

A review of the first year of Medicare coverage of erythropoietin.

Recombinant human erythropoietin (rHuEPO) is a new drug for treating anemia associated with end stage renal disease (ESRD). In a study of rHuEPO diffusion, costs, and effectiveness, we analyze ESRD program data and all claims submitted to Medicare for reimbursement of rHuEPO administered to ESRD dialysis patients. Access to rHuEPO was rapid and extensive during the first year of Medicare coverage. Dosing of rHuEPO and achieved hematocrit were lower than expected based on the results of clinical trials. rHuEPO cost Medicare $144 million in its first year. The analysis of insurance claims data allowed effective monitoring of access, costs, and effectiveness of this new biotechnology.

Black or African American↗
PubMed1994

The production of dialysis by for-profit versus not-for-profit freestanding renal dialysis facilities.

OBJECTIVE: A study was conducted to determine whether for-profit and not-for-profit freestanding renal dialysis facilities differ with respect to efficiency in the production of dialysis treatments. DATA SOURCES/STUDY SETTING: National data on 1,224 Medicare-certified freestanding dialysis facilities were obtained from the Health Care Financing Administration's (HCFA) 1990 Independent Renal Dialysis Facility Cost Report. Data on Medicare patients receiving care at these facilities during 1990 were obtained from HCFA's End Stage Renal Disease (ESRD) Program Management and Medical Information System (PMMIS). STUDY DESIGN: Ordinary least squares regression (OLS) was used to estimate the association between monthly output of dialysis treatments in 1990 and (a) facility capital and labor inputs, (b) facility ownership characteristics, and (c) case-mix characteristics. DATA COLLECTION/EXTRACTION METHODS: Facility and patient level data were extracted from the Facility Cost Report and the PMMIS databases, respectively. Patient level data were aggregated by facility and merged with facility level data. PRINCIPAL FINDINGS: For-profit sole proprietorships, for-profit partnerships and for-profit corporations each produced significantly more dialysis treatments per month than not-for-profits, adjusting for quantities of resource inputs and case-mix characteristics. CONCLUSION: For-profit facilities appear to be more efficient producers of dialysis treatments than not-for-profits. Further study should address whether other factors such as differences in severity of disease or in quality of care are responsible for these observations.

Ambulatory Care Facilities↗
PubMed1993

Medicare payment policy and recombinant erythropoietin prescribing for dialysis patients.

The Medicare payment policy for recombinant human erythropoietin (rHuEPO) treatment for dialysis patients changed in January 1991 from a relatively fixed payment per treatment (allowed charge of $40 per < or = 10,000 units injected) to a more variable payment based on the amount of rHuEPO administered with each treatment (allowed charge of $11 per 1,000 units injected). This change provided an opportunity to examine how payment policy can effect the use, cost, and health outcome of a biotechnology product used in the dialysis population. In cross-sectional (n = 71,880 Medicare-entitled dialysis patients) and longitudinal (n = 29,088 Medicare-entitled dialysis patients) study designs, we used Medicare end-stage renal disease program and claims data in bivariate and multivariate analyses to examine the effect of the change in payment policy for rHuEPO on access to the biotechnology, dosing, costs, and hematocrit, including the prescribing patterns at for-profit versus not-for-profit providers. The observation period included several months before (July 1989 to December 1990) and 6 months after (January to June 1991) the change in Medicare payment policy. The mean dose per treatment during the initial and fourth month of therapy was low (2,742 [95% confidence interval, 2,703 to 2,781] units and 2,632 [95% confidence interval, 2,598 to 2,667] units, respectively, in June 1990) and increased 3.4% and 5.0%, respectively, in the next 6 months prior to the change in Medicare payment policy compared with 14.6% and 14.8%, respectively, in the 6 months following the change in payment policy. The average monthly allowed charge for rHuEPO per dialysis patient receiving rHuEPO decreased from $455 before the policy change to $349 immediately following the policy change, because the allowed charge per unit of rHuEPO was lower when payment became more dependent on the amount of rHuEPO administered with each treatment than when the payment was fixed at $40 per treatment. The average monthly allowed charge for rHuEPO increased to $375 in the sixth month following the change in payment policy as a result of the increase in dose and the new variable payment. The unadjusted and adjusted changes in mean hematocrit 6 months after the payment change were positive but clinically very small (0.3 and 0.2 percentage points, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Early dosing practices and effectiveness of recombinant human erythropoietin.

In a national longitudinal-cohort study of 59,462 end-stage renal disease (ESRD) patients, we examined dosing and effectiveness of erythropoietin (EPO) during the first year of its use in clinical practice (July 1989 through June 1990). In unadjusted and multivariate analyses of Medicare claims data, the mean dose of EPO prescribed was: relatively small and similar for initial and maintenance therapy, 2752 (95% confidence interval 2740 to 2764) and 2668 (95% confidence interval 2654 to 2682) units, respectively; lower when initial therapy was started later (591 units lower in September 1989 and 760 units lower in November 1989 vs. July 1989, P < 0.0001); lower by 135 units during initial therapy and by 116 units during maintenance therapy for females (who weigh less) compared to males (P < 0.001); and lower by 400 units for patients treated in for-profit versus not-for-profit centers. In multivariate analysis: hematocrit response was less and mean maintenance dose was 298 units and 621 units greater for patients whose ESRD was due to multiple myeloma and sickle cell disease, respectively, compared to those with hypertension-related ESRD (P < 0.01); and hematocrit response was logarithmically related to dose [hematocrit = 0.97 ln (dose), P < 0.0001]. Forty-four percent of patients had a hematocrit > or = 30 after four months of therapy. The percent of patients transfused during three month periods before and after therapy decreased from 20% to 5%, respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Cost implications to Medicare of recombinant erythropoietin therapy for the anemia of end-stage renal disease.

The purpose of this study was to estimate the net cost effect to Medicare of the increasing use of recombinant human erythropoietin (EPO) instead of red blood cell transfusions or androgens in the management of anemia for the approximately 100,000 hemodialysis patients in the U.S. End-Stage Renal Disease (ESRD) program. A computerized decision model that takes into account the effectiveness and possible side effects of transfusions, androgens, and EPO and predicts 1- and 5-yr direct medical costs to Medicare associated with each therapy was constructed. Probability estimates for clinical events were derived from the literature. Costs were assigned by use of the amounts Medicare pays providers of ESRD care for: (1) use of EPO, transfusions, and androgens; and (2) health care services related to the treatment of anemia (including complications of treatment and possible reductions in morbidity). For every 10,000 hemodialysis patients treated with EPO, net Medicare expenditures will be much greater than if only transfusions are used by $42,530,000 at 1 yr (6% of ESRD program costs) and by $118,050,000 at 5 yr and also much greater than if androgens are used (by $42,700,000 at 1 yr and $118,370,000 at 5 yr). The increase in cost was highly sensitive to the dose of EPO; moderately sensitive to changes in estimated anemia response rates for EPO, frequency of EPO-induced vascular access clotting, and reduction in cardiovascular or overall morbidity; and slightly sensitive to transfusion rates, estimated anemia response rates for androgens, frequency of EPO-induced seizure or hypertensive complications (stroke, myocardial infarction), frequency of transfusion-related viral infection, and frequency of androgen-induced virilization. Considering both effectiveness and side effects of alternative treatments for the anemia of ESRD, it was projected that the increasing use of EPO will markedly increase the cost to Medicare of ESRD medical care.

Androgens↗
PubMed1993

Efficacy of immune globulin in preventing complications of bone marrow transplantation: a meta-analysis.

To assess the efficacy of immune globulin in preventing CMV infection, interstitial pneumonia, GVHD and death after BMT, we reviewed and synthesized data from 12 published studies (with 1282 patients) in which immune globulin was used prophylactically in BMT patients, controls were included and clinical outcomes were assessed. Data synthesis indicates that immune globulin significantly reduces fatal CMV infection (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.23-0.99), CMV pneumonia (OR 0.61, CI 0.42-0.89), non-CMV interstitial pneumonia (OR 0.57, CI 0.35-0.95) and total mortality (OR 0.74, CI 0.55-0.99). The reduction in acute GVHD was not quite significant (OR CI 0.45-1.02). Complications decrease with both hyperimmune and conventional immune globulin. For CMV-negative transplant recipients, immune globulin decreases symptomatic CMV infection (OR 0.55, CI 0.31-0.94) and interstitial pneumonia (OR 0.34, CI 0.15-0.77). For CMV-positive recipients, immune globulin prevents interstitial pneumonia (OR 0.45, CI 0.26-0.80) but not symptomatic CMV infection (CI 0.41-2.80). We conclude that immune globulin is efficacious in preventing major complications of BMT in both CMV-negative and CMV-positive recipients.

Adult↗
PubMed1993

Factors influencing third party payer costs for allogeneic BMT.

To assess how payer costs for allogeneic BMT relate to patient characteristics and clinical complications, a retrospective cohort study of 402 persons undergoing allogeneic BMT between 1980 and 1987 at a university-based BMT center was designed to determine total inpatient payer costs, including hospital and physician costs, and number of days hospitalized during the first 180 days following BMT. The average total inpatient payer cost (in 1990 dollars) during the first 180 days following BMT was $208,410. Inflation-adjusted inpatient payer costs increased from $227,806 in 1980 to $308,545 in 1983, and then decreased to $156,163 by 1987. In multivariate analysis, inpatient payer costs were strongly associated with occurrence of CMV infection (increase of $53,517; p = 0.0001) or acute GVHD (increase of $46,500; p = 0.001), and significantly associated with malignant (versus non-malignant) disease (decrease of $36,633; p = 0.05), even after adjusting for length of survival and year of BMT. Inpatient payer costs were not related to patient age, sex or race. Despite recent reductions in inpatient payer costs for BMT, CMV infection and acute GVHD continue to be associated with tremendous costs to third party payers. Further reductions in the costs of BMT may require improved prevention of CMV infection and GVHD.

Adolescent↗
PubMed1992

Access to recombinant erythropoietin by Medicare-entitled dialysis patients in the first year after FDA approval.

OBJECTIVE: Examine access to recombinant human erythropoietin (rHuEPO) by dialysis-dependent end-stage renal disease (ESRD) patients during the first year after FDA approval for use in clinical practice and Medicare coverage. DESIGN: Longitudinal and cross-sectional claims data analyses. SETTING: All US providers of outpatient dialysis treatment. PATIENTS: 126,201 Medicare-entitled dialysis patients (approximately 93% of all US dialysis patients). OUTCOME MEASURES: Percentage of patients who received rHuEPO, odds of receiving rHuEPO according to patient characteristics, and cost of rHuEPO to Medicare. RESULTS: One year after FDA approval, 52% of all dialysis and 60% of in-center hemodialysis patients who regularly had Medicare-paid dialysis services received rHuEPO at a monthly cost to Medicare of $19 million (18% of Medicare ESRD outpatient expenditures and 6% of all ESRD program expenditures). Blacks were less likely than whites to receive rHuEPO (odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91). Home peritoneal and hemodialysis patients were less likely than in-center hemodialysis patients to receive rHuEPO (odds ratios, 0.17 and 0.22, respectively; 95% confidence intervals, 0.16 to 0.17 and 0.20 to 0.24, respectively). Use of rHuEPO varied across geographic regions. The odds of receiving rHuEPO were lower for patients of male vs female sex, of ages 35 through 64 years vs less than 35 years and greater than 65 years, with a longer history of ESRD, with polycystic kidney disease vs other causes of ESRD, and receiving care in nonprofit vs for-profit facilities. First-month hematocrits were slightly higher (1.2 percentage points) for patients starting rHuEPO in the 12th month than in the first month after FDA approval. CONCLUSIONS: With prompt insurance coverage, the majority of Medicare-entitled dialysis patients received rHuEPO following widespread availability. Factors that may not be related to clinical need (race, setting of care, and geography) possibly influenced early patient access. More attention should be paid to monitoring the appropriate use of high-cost biotechnologic therapy.

Adolescent↗
PubMed1992

Functional importance of a highly elastic ligament on the mammalian diaphragm.

The diaphragm of mammals is a musculotendinous dome separating the thoracic and abdominal cavities. With no skeletal elements to stretch it, the diaphragm has the problem of positioning its muscle fibres at a length appropriate for the onset of an inspiratory contraction. This is achieved through a negative intrapleural pressure, resulting from the opposing elastic recoil of the ribcage and lungs, which sucks the diaphragm into the thorax and extends the muscle fibres. A consequence of this negative pressure is that the diaphragm muscle is under tension when inactive during expiration. This is an unusual condition for skeletal muscles, which can suffer irreversible changes when stretched to long length, or they may respond by growing longer. We now describe a highly elastic and resilient diaphragmatic ligament which sets a sarcomere length enabling the muscle to use its full operating range, reduces stress on the diaphragm muscle fibres, and assists shortening of the diaphragm muscle at the onset of inspiration by means of elastic recoil.

Animals↗
PubMed1991

Shortening of muscle fibres during stretch of the active cat medial gastrocnemius muscle: the role of tendon compliance.

1. The length of muscle fibres in the medial gastrocnemius (MG) muscle of the anaesthetized cat was measured using ultrasound techniques. During the course of 'isometric' contractions, the muscle fibres shortened by stretching the compliant tendons, until the muscle fibres could no longer produce enough force to stretch the tendons further. At optimal muscle length (Lo) the maximal shortening of muscle fibres was 28%. 2. At muscle lengths much longer than Lo, 'isometric' contractions produced a slow shortening of the muscle fibres as the tendons were stretched and this resulted in a slow rise in tension. This phenomenon, usually referred to as 'creep', is due to low power at long muscle fibre length. This study shows that the series compliance present in the tendons is the major contributor to 'creep' in the cat MG muscle. As the tendons stretched during the course of the contraction, the average sarcomere length became shorter providing greater filament overlap and increasing power. 3. Slow to medium speed stretches applied shortly after the onset of contraction, as occurs in cat MG during walking and trotting, were entirely taken up in the tendons and the muscle fibres actually shortened throughout the imposed muscle stretch. 4. When early stretches were applied at muscle lengths longer than Lo, stretch of the muscle resulted in a peak force that was less than if the stretch had not been applied. This was the reverse of the situation for stretches at lengths less than Lo. When stretch was applied after attaining peak force, the force was greatly enhanced and the muscle fibres were also stretched. 5. Using the same techniques in a freely walking cat, the muscle fibres shortened by 1.0 +/- 0.3 mm during the stance phase of the step-cycle when the muscle was being stretched, in 198 consecutive step-cycles. 6. The tendons act as a mechanical buffer to protect muscle fibres from damage during eccentric contractions. 7. Since stretches of the MG muscle are not faithfully imposed on the muscle fibres, studies of muscle spindle function during locomotion need to take into consideration these effects of tendon compliance. The dominant view, when the foot lands on the ground during normal locomotion, is that muscle spindles are stretched along with the muscle resulting in reflex enhancement of contractile force. This study shows that the muscle fibres do not stretch under these circumstances, except at high speeds of locomotion when the stretch rate is also high.

Animals↗
PubMed1989

Roles of muscle activity and load on the relationship between muscle spindle length and whole muscle length in the freely walking cat.

The objective of this research was to compare the length of muscle spindles to the length of the whole muscle, during normal movements. Pairs of piezoelectric crystals were implanted near the origin and insertion of muscle fibres in the medial gastrocnemius (MG) muscle of cats. The distance between crystals was measured with pulsed ultrasound, the origin-to-insertion length of the MG muscle was measured with a transducer made of saline-filled silicone tubing, MG force was measured with a tendon force transducer and EMG activity was selectively recorded in the vicinity of implanted crystals. These signals were simultaneously recorded during posture or locomotion on a motorized treadmill. Three periods were identified in the step cycle, during which the relation between muscle length and spindle length changed dramatically. In period I (roughly corresponding to the late F and E1 phases of swing), the MG muscle and spindles followed similar length changes: both were stretched and then shortened by about 6 mm. In period II (corresponding to the stance phase, E2-E3) the MG muscle yielded under the weight of the body and was stretched by 1-3 mm, whereas the MG spindles typically continued shortening. In period III, the MG muscle shortened rapidly by 6-8 mm after the foot left the ground and then stretched again by about the same amount, whereas the spindles could remain nearly isometric. We attribute these large discrepancies in muscle and spindle length to the architecture of the MG muscle and the compliance of long tendinous elements in series with the spindles. We conclude that the length changes imposed on muscle spindles during voluntary movements are not simply related to the parent muscle length changes and cannot be estimated without taking into account the muscle architecture, the location of the spindle within the muscle, the level of muscle activation and the external load.

Animals↗
PubMed1987

Ultrasound transit time gives direct measurement of muscle fibre length in vivo.

The movement occurring in whole muscle during contraction is divided between the muscle fibres, the tendon and the longitudinal change in length due to a change in pennation angle. The relative importance of each of these components varies between muscles and with how they are being used. To date it has not been possible to measure each of these movements. By suturing piezoelectric crystals to each end of a small group of muscle fibres in cat medial gastrocnemius muscle, the transit time of ultrasound between the crystals was measured. Assuming a constant velocity of sound in muscle of 1580 m/s, the transit time was used to calculate the muscle fibre length. In "isometric" tetanic contractions the muscle fibres shortened by up to 25% at the expense of the tendons. Lengthening the muscle by 4 mm between each two tetanii, produced less than 4 mm stretch of the muscle fibres as some of the movement was taken up by a change in pennation angle. Except at long lengths, when passive tensions were present, none of this movement between tetanii could be accounted for by stretch of the tendon.

Animals↗
PubMed1978

Local cerebral blood flow and the electrocorticogram during sodium nitroprusside hypotension.

Changes in local cerebral blood flow during sodium nitroprusside hypotension were measured using the hydrogen electrode technique. At mean arterial pressures from 90% to 50% of control values, local cerebral blood flow showed a significant decrease by 20%. When blood pressure was reduced below 50%, the local cerebral blood flow increased significantly and approached control levels. It is suggested that the flow increase may be due to local hypoxia. Associated with this increase were electrocorticogram changes indicative of hypoxia. The significant decrease in mean local cerebral blood flow and the large range of flows seen during mild hypotension indicate that autoregulation is impaired. During hypotension, intracranial pressure increased by, at most, 3 mm Hg. Cardiac output was usually unaffected and was never decreased by more than 20%.

Animals↗