Real-world treatment patterns in resectable (stages I-III) non-small-cell lung cancer: a systematic literature review.

Aim: The aim of this systematic literature review was to describe treatment patterns in nonmetastatic non-small-cell lung cancer. Methods: A search was conducted in MEDLINE and EMBASE. Eligible studies were multicentered (>50 patients) and conducted after 2000 in North America, Europe and Asia. Results: Twenty studies met the eligibility criteria. Based on US and Canadian studies in the resectable population, the proportion of patients who received neoadjuvant chemotherapy/chemoradiotherapy and adjuvant chemotherapy/chemoradiotherapy increased with increasing stage (i.e., from <3% in stage I to about 40% in stage III and from 15% in stage I to 30% in stage III, respectively). Within the resectable population, the breakdown between bimodal and trimodal therapy was variable, suggesting that clinical practice is not uniform. Conclusion: Overall, studies were heterogeneous, precluding data extrapolation across regions. Despite heterogeneity and limited evidence, this review suggested an increase in neoadjuvant and adjuvant chemotherapy with increasing stage, generally in line with treatment guidelines.

This literature review aimed to describe the treatment patterns in nonmetastatic non-small-cell lung cancer. This review was performed according to the highest methodological standards and searched published and unpublished records of stages I­III non-small-cell lung cancer treatment in North America, Europe and Asia. A limited number of studies were identified showing that in North America treatment with neoadjuvant and adjuvant chemotherapy (with or without radiotherapy) increased with stage. Identified studies in all regions showed that the treatment received, such as bimodal with surgery and chemotherapy compared with trimodal with surgery, chemotherapy and radiotherapy, was quite variable and that practice was not uniform. Overall, the studies were heterogeneous and data could not be extrapolated to practice across all regions. However, the studies suggested an increase in neoadjuvant and adjuvant usage with increasing stage, which is generally in line with treatment guidelines.

Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up.

OBJECTIVES: Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non-small-cell lung cancer (NSCLC). METHODS: Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs-landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)-were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. RESULTS: For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). CONCLUSIONS: We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. HIGHLIGHTS: Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up.Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes.Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data.Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting.Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup.

Role of IncP-1ß plasmids pWDL7::rfp and pNB8c in chloroaniline catabolism as determined by genomic and functional analyses.

Broad-host-range catabolic plasmids play an important role in bacterial degradation of man-made compounds. To gain insight into the role of these plasmids in chloroaniline degradation, we determined the first complete nucleotide sequences of an IncP-1 chloroaniline degradation plasmid, pWDL7::rfp and its close relative pNB8c, as well as the expression pattern, function, and bioaugmentation potential of the putative 3-chloroaniline (3-CA) oxidation genes. Based on phylogenetic analysis of backbone proteins, both plasmids are members of a distinct clade within the IncP-1ß subgroup. The plasmids are almost identical, but whereas pWDL7::rfp carries a duplicate inverted catabolic transposon, Tn6063, containing a putative 3-CA oxidation gene cluster, dcaQTA1A2BR, pNB8c contains only a single copy of the transposon. No genes for an aromatic ring cleavage pathway were detected on either plasmid, suggesting that only the upper 3-CA degradation pathway was present. The dcaA1A2B gene products expressed from a high-copy-number vector were shown to convert 3-CA to 4-chlorocatechol in Escherichia coli. Slight differences in the dca promoter region between the plasmids and lack of induction of transcription of the pNB8c dca genes by 3-CA may explain previous findings that pNB8C does not confer 3-CA transformation. Bioaugmentation of activated sludge with pWDL7::rfp accelerated removal of 3-CA, but only in the presence of an additional carbon source. Successful bioaugmentation requires complementation of the upper pathway genes with chlorocatechol cleavage genes in indigenous bacteria. The genome sequences of these plasmids thus help explain the molecular basis of their catabolic activities.

Payment, compensation and replacement--the ethics and motivation of blood and plasma donation.

The supply of blood and plasma to produce haemotherapies varies around the world, but all environments need donors to furnish the raw material. Many countries still lack adequate supply, and the question of what amounts of blood and plasma are required for optimal treatment is still unresolved. The issue of compensating donors has been a controversial and emotive one in blood transfusion for many decades. Donors are conventionally classified as paid, voluntary or replacement, and a level of stigma, based on safety and ethical considerations, has been attached to paid donation. This review points to evidence which renders many of these concerns redundant. Purist arguments against compensated donation have little basis in evidence and would lead to many of today's voluntary donors being designated as paid, because of the large range of incentives used to recruit and retain them. Misplaced application of 'Titmussian' volunteerism has precipitated its own safety and supply problems. Current systems of compensation and replacement are needed to maintain supplies of essential products and lead to safe products in controlled environments. We propose that a plurality of routes towards donation is an appropriate paradigm in the heterogeneous landscape of blood and plasma product supply.

Gestational diabetes mellitus screening and diagnosis: a prospective randomised controlled trial comparing costs of one-step and two-step methods.

OBJECTIVE: To conduct a cost minimisation analysis of three methods of gestational diabetes mellitus (GDM) screening and diagnosis. DESIGN: Prospective randomised controlled trial. SETTING: University teaching hospital. POPULATION: Pregnant women (n = 1594) presenting for GDM screening. METHODS: Women presenting for GDM screening, who consented to participate, were randomised to GR1 [1-hour, 50-g glucose screen (GS) +/- 3-hour, 100-g oral glucose tolerance test (OGTT)], GR2 (50-g GS +/- 2-hour, 75-g OGTT) or GR3 (2-hour, 75-g OGTT). Demographics, health and time/travel cost information were assessed for each glucose testing visit. MAIN OUTCOME MEASURES: Costs (direct and indirect) and prevalence of GDM diagnosis. RESULTS: The direct sampling costs of the glucose tests per woman were as follows: GS, CAN$12.57; 75-g OGTT, $36.10; 100-g OGTT, CAN$48.13. Among women in the two-step method groups diagnosed with GDM, 39% of the GR1 and 61% of the GR2 groups were diagnosed at the first step by GS > or = 10.3 mmol/l, according to the Canadian Diabetes Association recommendations, contributing to a lower total cost in these groups. The total costs per woman screened were as follows: GR1, CAN$91.61; GR2, CAN$89.03; GR3, CAN$108.38. The GDM prevalence was similar (3.7%, 3.7% and 3.6%, respectively). The higher costs of GR3 were related to more blood draws and the time required for all women to undergo the 2-hour OGTT. CONCLUSIONS: Careful consideration should be given to an internationally recommended method of universal screening for GDM which minimises the burden and cost for individual women and the healthcare system, yet provides diagnostic efficacy. The two-step method (GS +/- OGTT) accomplished this better than the one-step method (75-g OGTT).

Cost-effectiveness of mandibular two-implant overdentures and conventional dentures in the edentulous elderly.

Implementation of new therapies is usually governed by financial considerations, so efficacy studies should also include cost comparisons. The cost and effectiveness of mandibular conventional dentures (CD, n = 30) and two-implant overdentures (IOD, n = 30) were compared in elderly subjects. Effectiveness (Oral Health Impact Profile, OHIP-20) and cost were measured up to one year post-treatment. Data for subsequent years were estimated by the Delphi method. Using an average life expectancy of 17.9 years, the equalized annual costs (in Canadian dollars) were dollar 399 for CD and dollar 625 for IOD (p < 0.001), and the equalized annual values for the outcome (OHIP-20) were 47.0 for CD and 31.3 for IOD treatment (p < 0.05). These values translate into a yearly additional cost for IOD treatment of dollar 14.41 per OHIP-20 point. These results are key to the implementation of programs to provide this form of therapy for edentulous adults.

Co-morbidity and physician use in fibromyalgia.

OBJECTIVE: To describe comorbidity in women with FM, and to examine the effects of different types of comorbidity on physician use. METHODS: Women (n = 180) with primary FM were evaluated at baseline and 6 months later for self-reported health resource use and covariates. Reported comorbidity was classified into 4 categories: medical, psychiatric, "functional", and unknown. The category for "functional" conditions included disorders that have been classified by previous authors as medically unexplained symptoms such as the irritable bowel and chronic fatigue syndromes. Logistic regression models were developed to examine associations between types of comorbidity and physician use. RESULTS: Comorbid conditions were reported by over 90% of the sample. Total number of comorbid complaints was associated with high number of physician visits. In logistic regression models (controlling for age, ethnicity, education, disability, pain, and psychological vulnerability) medical comorbidity was a much stronger determinant of high number of physician visits than was "functional" comorbidity. CONCLUSIONS: Comorbidity with other disorders, both functional and medical, was high in this sample. Medical and psychiatric comorbidity were stronger determinants of high physician use than "functional" comorbidity.

Volatility in Medicare AAPCC rates: 1990-1997.

As Medicare beneficiary enrollment in managed care plans increases, and as Congress considers relying on capitation for achieving savings in the program, the question of finding a fair and equitable formula for determining the monthly payment to managed care plans has become increasingly salient. This DataWatch focuses on one dimension of using previous expenditures to determine annual capitation rates: the effects of historic volatility in total expenditures. Annual changes in adjusted average per capita cost (AAPCC) rates are especially dramatic in rural counties, with those not adjacent to urban areas experiencing the greatest volatility. This pattern of annual change may discourage managed care organizations from entering markets, even when the rate in any given year may appear to be favorable for accepting risk.

Promoting self-directed hemodialysis: measurement and cognitive-behavioral intervention.

Approximately 98% of hemodialysis patients who are treated in hemodialysis units currently use staff-directed treatment. This may well be the most expensive and most dependent mode of hemodialysis treatment. If an effective strategy were developed to enhance degree of self-directed care, millions of public health dollars might be saved while patients reap potentially substantial psychological benefits. The present research took two steps in the direction of promoting increased self-directed treatment of hemodialysis. First, a reliable and easily used behavioral observation system was developed to define and measure degree of self-directed treatment of hemodialysis. Second, a five-step cognitive-behavioral strategy to improve degree of self-directed treatment was developed and tested preliminarily. The strategy includes an initial rationale, decisional counseling, behavioral contracting, self-monitoring, and staff support/problem solving. Four nurses used this approach with 4 elderly patients (mean age = 70.5 years). A multiple-baseline-across-subjects design revealed substantial and relatively rapid improvements in degree of self-directedness associated with the intervention for the 3 patients who remained healthy throughout the study. The discussion focuses on the implications of the results for future research.

Geographic variation in determinants of Medicare managed care enrollment.

OBJECTIVE: To examine the effect of adjusted average per capita cost (AAPCC) rate and volatility on Medicare risk plan enrollment at the county level. DATA SOURCES: Secondary data from the Health Care Financing Administration's office of managed care and other sources were merged to create comprehensive data on all Medicare risk plans in 3,069 of the 3,112 U. S. counties in December 1996. STUDY DESIGN: A two-step least squares regression was estimated to examine the effects of AAPCC rate and volatility, commercial HMO enrollment, market factors, and characteristics of the county population on Medicare HMO enrollment. The model was also used to simulate the effects of the Balanced Budget Act of 1997. Data from the Health Care Financing Administration were merged with other sources at the county level. The Federal Information Processing Standards code and a crosswalk file matching that code with the county name linked the data across sources. PRINCIPLE FINDINGS: The AAPCC rate has a small positive effect on the probability of Medicare HMO availability and enrollment. However, commercial HMO enrollment has a much stronger positive effect on Medicare HMO enrollment. Volatility has a negative effect on the probability of any Medicare HMO enrollment. CONCLUSIONS: The results suggest that payment changes enacted as part of the Balanced Budget Act will have a limited effect on Medicare HMO enrollment, especially in rural areas. Other policy changes are needed to stimulate Medicare HMO enrollment.

Effects of post-hospital Medicare home health and informal care on patient functional status.

OBJECTIVE: To examine the effect of post-hospital Medicare home health and informal care on the functional status of 755 Medicare beneficiaries six weeks after hospital discharge for treatment of stroke, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hip procedures, and hip fractures. STUDY SETTING/DATA SOURCES: Consecutive patients enrolled in the study between March 1988 and February 1989 prior to discharge from one of 52 hospitals in three cities. Data sources included patient interviews, medical records, and the Medicare Automated Data Retrieval System (MADRS). ANALYSIS: The effect of the two types of care on patients' subsequent functional status was estimated using a selectivity corrected least squares regression of functional status six weeks post-discharge on hours of informal care, Medicare home health expenditures, and patient prior functional and cognitive status. DATA COLLECTION/EXTRACTION METHODS: Patients were interviewed before hospital discharge and six weeks later. The patient's primary caregiver was interviewed by telephone six weeks post-discharge. Patient data included demographic characteristics, illness severity, cognitive status, functional status at discharge and six weeks later, post-discharge expenditures for Medicare home health, and hours of informal care. PRINCIPAL FINDINGS: More informal care after discharge was associated with greater patient functional impairment six weeks later. The amount of Medicare home health that patients used had a nonsignificant effect on subsequent functional status. CONCLUSIONS: Post-acute home care may maintain the patient at home and compensate for functional limitations, rather than promote restoration of function. Future studies are needed to examine the effects of specific types of care, services, and providers as well as factors that mediate their effects on patient functional outcomes.

Modeling the costs of case management in long-term care.

A conceptual approach to developing models for analyzing cost is applied to case management in long-term care. This conceptual approach uses four dimensions to classify case management programs. The application results in identifying five case management cost models. Empirical measures of case management costs and a set of determinants of the within-model variation in these costs are suggested for each model. This article discusses several policy relevant hypotheses that could be addressed by the empirical implementation of these cost models.

Who cares? The size, scope, and composition of the caregiver support system.

The informal care networks of 242 impaired older people were examined in terms of the primary caregiver and secondary helpers. Most primary caregivers had at least one secondary helper; 88% identified helpers who provided hands-on help, 19% reported that helpers contributed financially, and 44% had helpers involved in care decisions. The size of the network was larger for direct care compared to financial or decision-making assistance. Almost half of primary caregivers reported that their spouse helped. It was expected that after controlling for characteristics of the primary caregiver and of the older person, that characteristics of the secondary caregiver network would influence the amount and type of primary caregiver assistance and formal care used by the older person. However, both hours and type of care by the primary caregiver were independent of size, scope, and composition of the secondary helper network. This independence suggests that efforts to alter the secondary caregiver network may have limited effects on the primary caregiver.

Evaluating the efficiency and effectiveness of approaches to nasogastric tube insertion during trauma care.

BACKGROUND: Numerous invasive, uncomfortable, and discomforting procedures are implemented almost routinely during trauma care. Previous research has shown that trauma care practitioners use comforting strategies during this care. Yet little is known of the effect of these comforting strategies on the effectiveness and efficiency of treatment. OBJECTIVES: To evaluate the effect of the caregiver's approach on the efficient and effective completion of a discomforting procedure (nasogastric tube insertion) on conscious patients during trauma care. METHODS: Ethology was used to analyze 32 attempts at nasogastric tube insertion from 193 videotaped trauma cases from 3 level I trauma centers in North America. Both qualitative and quantitative analytic techniques were used. RESULTS: The practitioner's approach was associated with the outcome of the treatment. Overall, practitioners who balanced the technical aspects of the procedure with use of comforting strategies to minimize the patient's discomfort (the blended approach) were most efficient and most effective in completing this procedure. Practitioners who were most attentive to procedural technique (with little respect to patients' discomfort) or who were overly attentive to comforting strategies (termed the technical and affective approaches, respectively) took longer and/or were less successful at completing the procedure. CONCLUSIONS: Four patterned, standardized approaches to care were found: technical, affective, blended, and mixed. This study has implications for further research into the effect of the practitioner's approach on the patient's behavioral state in trauma care.

Functional disability at nursing home admission: a comparison of urban and rural admission cohorts.

This study's objective was to examine the relationships between rural residence and availability of nursing home and home health care to functional disability at the time of nursing home admission. Secondary data were obtained from the Minimum Data Set (MDS) 2.0 for Nebraska for 3,443 rural and 1,296 urban older people admitted to nursing facilities. Data from the MDS were merged with county-level data on home health agencies and nursing homes in Nebraska. The relationship of rurality of nursing home residents' prior residence and availability of nursing home and home health care to functional status at admission, controlling for demographic and health characteristics of older people, was estimated using multiple linear regression with robust variance estimates. After taking account of demographic and health status characteristics, rural residence and availability of home health and nursing home care had nonsignificant effects on functional status at admission. The findings indicate that functional disability at admission is associated with specific diseases and medical conditions, cognitive status, gender, living arrangements and marital arrangements. Rural older people are not at higher risk of admission at lower levels of functional disability compared to their urban counterparts.

Strategies for assessing and fostering hope: the hope assessment guide.

PURPOSE/OBJECTIVES: To detail behavioral manifestations of hope and to present the Hope Assessment Guide with stage-specific nursing strategies to foster the development of hope. DATA SOURCES: Previous research and a concept analysis of hope, including interviews with survivors of breast cancer, people awaiting heart transplants, breast-feeding mothers returning to work, and patients with spinal cord injuries. Criteria for inclusion included empirical validity of the conceptual framework, power of the autobiographic data to illustrate theoretical fit, and usefulness of the theory in assessing hope and devising clinical strategies. DATA SYNTHESIS: Behavioral manifestations within reported breast cancer experiences demonstrated theoretical fit. From this, the researchers extracted assessment factors and identified clinical strategies based on reported experiences and strategies found helpful at various stages of the hope development process. CONCLUSIONS: The conceptual model provides structure for assessing and responding to developing hopefulness in a stage-specific manner. IMPLICATIONS FOR NURSING PRACTICE: By becoming aware of the processes of developing hope, nurses are better prepared to clinically assess this dynamic process and to devise highly individualized clinical interventions in cases in which hope needs to be supported or modified.

Family practice residency programs and the graduation of rural family physicians.

BACKGROUND AND OBJECTIVES: Family practice residency programs graduate about 600 rural physicians each year. Increases in resident positions have not increased the numbers who choose rural practice. This study examines the relationship between program characteristics and the graduation rate of rural physicians. METHODS: From 1994-1996, we sent an annual survey to the directors of all nonmilitary family practice residency programs; 353 programs (96% response rate) returned questionnaires. Weighted least-squares regression was used to analyze the relationship between program factors and the percentage of graduates who chose practices in 1992, 1993, and 1994 in towns of less than 25,000 not adjacent to a larger metropolitan area. RESULTS: Family practice residency programs that graduated more rural physicians had more required rural and obstetrical training months, had a full or partial rural mission, were located in more rural states, had the program director as the rural contact, had a procedural emphasis, had fewer residents who were minorities or female, and used fewer types of other major graduate programs for rotations. CONCLUSIONS: This study outlines the important contribution of rural emphasis and training in family practice residency programs. Future studies should explore rural, procedural, and obstetrical training interventions and examine gender, minority, and program location issues.

Caregivers' experiences in making placement decisions.

Demographic trends indicate a growth in the older adult population, and in turn, are affecting the availability and use of health services. Although placement of an older adult charge into nursing home care is often described as a logical progression through the continuum of available services, informal caregivers often view placement as a last resort or as an indication of failure. This qualitative study used grounded theory methods to explore the experiences of caregivers actively involved in the process of placing an older adult in a long-term care facility upon discharge from acute care. Four themes (uncertainty, surrendering to the system, urgency, and validating) were interwoven throughout caregivers' perspectives of the conflictive decision to use nursing home care after hospitalization.