Variation in expenditure for common, high cost surgical procedures in a working age population: implications for reimbursement reform.

BACKGROUND: In the move toward value-based care, bundled payments are believed to reduce waste and improve coordination. Some commercial insurers have addressed this through the use of bundled payment, the provision of one fee for all care associated with a given index procedure. This system was pioneered by Medicare, using a population generally over 65 years of age, and despite its adoption by mainstream insurers, little is known of bundled payments' ability to reduce variation or cost in a working-age population. This study uses a universally-insured, nationally-representative population of adults aged 18-65 to examine the effect of bundled payments for five high-cost surgical procedures which are known to vary widely in Medicare reimbursement: hip replacement, knee replacement, coronary artery bypass grafting (CABG), lumbar spinal fusion, and colectomy. METHODS: Five procedures conducted on adults aged 18-65 were identified from the TRICARE database from 2011 to 2014. A 90-day period from index procedure was used to determine episodes of associated post-acute care. Data was sorted by Zip code into hospital referral regions (HRR). Payments were determined from TRICARE reimbursement records, they were subsequently price standardized and adjusted for patient and surgical characteristics. Variation was assessed by stratifying the HRR into quintiles by spending for each index procedure. RESULTS: After adjusting for case mix, significant inter-quintile variation was observed for all procedures, with knee replacement showing the greatest variation in both index surgery (107%) and total cost of care (75%). Readmission was a driver of variation for colectomy and CABG, with absolute cost variation of $17,257 and $13,289 respectively. Other post-acute care spending was low overall (≤$1606, for CABG). CONCLUSIONS: This study demonstrates significant regional variation in total spending for these procedures, but much lower spending for post-acute care than previously demonstrated by similar procedures in Medicare. Targeting post-acute care spending, a common approach taken by providers in bundled payment arrangements with Medicare, may be less fruitful in working aged populations.

Long-term follow-up of patients immunized with AN1792: reduced functional decline in antibody responders.

BACKGROUND: Immunization of patients with Alzheimer's disease (AD) with synthetic amyloid-beta peptide (Abeta(42)) (AN1792) was previously studied in a randomized, double-blind, placebo-controlled phase 2a clinical trial, Study AN1792(QS-21)-201. Treatment was discontinued following reports of encephalitis. One year follow-up revealed that AN1792 antibody responders showed improvements in cognitive measures as assessed by the neuropsychological test battery (NTB) and a decrease in brain volume compared with placebo. METHODS: A follow-up study, Study AN1792(QS-21)-251, was conducted to assess the long-term functional, psychometric, neuroimaging, and safety outcomes of patients from the phase 2a study 4.6 years after immunization with AN1792. The results were analyzed by comparing patients originally identified as antibody responders in the AN1792 phase 2a study with placebo-treated patients. RESULTS: One hundred and fifty-nine patients/caregivers (30 placebo; 129 AN1792) participated in this follow-up study. Of the 129 AN1792-treated patients, 25 were classified in the phase 2a study as antibody responders (anti-AN1792 titers > or = 1:2,200 at any time after the first injection). Low but detectable, sustained anti-AN1792 titers were found in 17 of 19 samples obtained from patients classified as antibody responders in the phase 2a study. No detectable anti-AN1792 antibodies were found in patients not classified as antibody responders in the phase 2a study. Significantly less decline was observed on the Disability Assessment for Dementia scale among antibody responders than placebo-treated patients (p=0.015) after 4.6 years. Significant differences in favor of responders were also observed on the Dependence Scale (p=0.033). Of the small number of patients who underwent a follow-up MRI, antibody responders showed similar brain volume loss during the follow-up period subsequent to the AN1792 phase 2a study compared with placebo-treated patients. CONCLUSIONS: Approximately 4.6 years after immunization with AN1792, patients defined as responders in the phase 2a study maintained low but detectable, sustained anti-AN1792 antibody titers and demonstrated significantly reduced functional decline compared with placebo-treated patients. Brain volume loss in antibody responders was not significantly different from placebo-treated patients approximately 3.6 years from the end of the original study. No further cases of encephalitis were noted. These data support the hypothesis that Abeta immunotherapy may have long-term functional benefits.

Exploring prison buprenorphine misuse in the United Kingdom: a qualitative study of former prisoners.

The United Kingdom Ministry of Justice recently highlighted the extent of buprenorphine (Subutex) misuse in English andWelsh prisons, naming it the third most misused drug overall. Yet little is known regarding how illicit buprenorphine is obtained in prison and what influences prisoners to use it. Qualitative research was used to explore prison drug using practices. Thirty men who were former prisoners with a history of injecting drug use were interviewed in depth about their illicit prison drug use, including buprenorphine. Interviews were conducted over 18 months, from August 2006 to January 2008 and were analysed using Framework. The misuse of Subutex by snorting emerged as a significant theme. Accounts suggested that the diversion of prison prescribed Subutex was widespread and prisoners used various tactics to obtain the medication. Various complex and interlinked reasons were given to explain why Subutex was snorted in prison. The main motivation for snorting was to experience a prolonged euphoric opiate effect, believed to help to combat the boredom of being in prison. The price of illicit Subutex in prison was linked to its availability, but it was generally cheaper than heroin, thus contributing to its use. Participants'narratives identified the belief that snorting Subutex in prison was not risk free, but risks were lower than continuing to use other drugs, particularly injecting illicit opiates. The implications of prison Subutex misuse for prisoners, prison medical services, commissioners, and prescribing policy and practice are discussed.

Non-commercial clinical trials of a medicinal product: can they survive the current process of research approvals in the UK?

Over recent years, considerable attention has been paid to the National Health Service (NHS) research governance and ethics approvals process in the UK. New regulations mean that approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) is now also needed for conducting all clinical trials. Practical experience of gaining MHRA and sponsorship approval has yet to be described and critically explored in the literature. Our experience, from start to finish, of applying for these four approvals for a multicentre randomised controlled trial of two licensed drugs for opiate detoxification in the prison setting is described here. In addition, the implications of the approvals process for research projects, particularly clinical trials, in terms of time and funding, and also indirect implications for NHS patients are discussed. Inconsistencies are discussed and suggestions that could improve and streamline the overall process are made. The current approvals process could now be hindering non-commercial clinical trials, leading to a loss of important evidence-based medical information.

Comparison of conventional and accelerated hepatitis B immunisation schedules for homeless drug users.

This historical control study examines the uptake of two hepatitis B immunisation schedules at an inner city primary care centre for homeless people in Northern England. Originally homeless patients disclosing current or past illicit drug use were offered hepatitis B immunisation. In 1999 a conventional hepatitis B vaccine schedule was offered (immunisations at 0, 1, and 6 months) whereas in 2000 an accelerated schedule was introduced (immunisations at 0, 7 and 21 days). There was an increase in the uptake of hepatitis B vaccination by homeless drug users once the accelerated schedule was introduced. Furthermore, the completion rates for the accelerated vaccination regimen were almost seven times higher than for the conventional one. This indicates that the accelerated hepatitis B schedule should be the regime of choice for patients with a current or past history of drug use.

Balancing diversion control and medical necessity: the case of prescription drugs with abuse potential.

Narcotics and other prescription drugs play a significant and legitimate role in medical practice. The illicit use of prescribed medicines, however, remains a major problem. This paper examines the effectiveness of two drug diversion control programs, multiple copy prescriptions programs (MCPP) and electronic data transfer (EDT) systems, and their impact on medical practice. Current evidence demonstrates that these programs decrease prescription drug use, with much of the decrease due to declines in inappropriate use. MCPPs appear more effective than EDT in preventing diversion. More research is needed. however, to assess their effects on medical practice, particularly patient quality of care.

Predictive inferencing in adults with right hemisphere brain damage.

Predictive inferencing was evaluated in 13 adults with right hemisphere damage (RHD) and 11 adults without brain damage (NBD). Brief narrative stimuli that strongly suggested a single outcome were constructed to vary recency of mention of inference-related information. Reading times were recorded for narrative-final sentences that disconfirmed the target inferences. Slowed reading time on the final sentences was an indicator of inference generation. Adults with RHD generated target predictive inferences in contexts with recent mention of strongly biasing inference-related information. This group also evidenced maintenance of inferences over time, but to a lesser degree than participants in the NBD group. Overall, individuals with better auditory comprehension or larger estimated working memory capacity tended to maintain inferences better than did the other participants. The results are discussed in relation to current hypotheses of inferencing and discourse comprehension in adults with RHD.

Mechanisms of discourse comprehension impairment after right hemisphere brain damage: suppression in inferential ambiguity resolution.

This study examined the generality of a previous finding indicating that difficulty suppressing or inhibiting context-inappropriate interpretations is an important predictor of narrative discourse comprehension for adults with right brain damage (RBD) (C. A. Tompkins, A. Baumgaertner, M. T. Lehman, & W. Fassbinder, 2000). Forty adults with RBD and 39 without brain damage listened to two-sentence stimuli and judged whether a probe word fit with the overall stimulus meaning. An ambiguous initial sentence elicited both dominant and less preferred inferences, and the second sentence resolved the ambiguity toward the initially less-likely interpretation. Probes represented the dominant inference for the first sentence and were presented at two poststimulus intervals. Probe judgment response times indicated that neither group suppressed the eventually inappropriate inferences in the time intervals studied. However, multiple regression analysis demonstrated that for individual participants with RBD, the extent of suppression from one interval to the next was a significant predictor of performance on a specialized measure of inference comprehension. The discussion evaluates these findings and identifies directions for future research.

Mechanisms of discourse comprehension impairment after right hemisphere brain damage: suppression in lexical ambiguity resolution.

Normal comprehension skill is linked with the proficiency of a suppression mechanism, which functions to dampen mental activation that becomes irrelevant or inappropriate to a final interpretation. This study investigated suppression and discourse comprehension in adults with right brain damage (RBD). To index suppression function, 40 adults with RBD and 40 without brain damage listened to sentence stimuli that biased the meaning of a sentence-final lexical ambiguity (e.g., SPADE), then judged whether a probe word (e.g., CARDS) fit the overall sentence meaning. Probes represented the contextually inappropriate meanings of the ambiguities and were presented in two conditions: 175 ms and 1000 ms post-stimulus. The same probes were used with unambiguous comparison stimuli. Probe judgment response times indicated that only the group without brain damage suppressed inappropriate interpretations over time. In a multiple regression analysis, suppression function added significantly to predicting performance on a general measure of narrative discourse comprehension for participants with RBD. The discussion addresses how suppression deficits may account more broadly for comprehension difficulties after RBD; it also considers several unresolved issues concerning the suppression construct and the suppression deficit hypothesis.

Student and faculty learning styles in a Canadian and a Chilean self-directed, problem-based nursing program.

A descriptive comparative study was conducted to identify and compare/contrast the learning styles of nursing faculty and entry-level students in 2 self-directed (SDL), problem-based (PBL) nursing programs. The Kolb LSI-1985 was administered to 94 first-year generic students, 63 post-R.N. students, and 22 faculty members in a Canadian university nursing program. A Spanish translation was completed by 37 incoming nursing students and 13 faculty members in a Chilean university. One-way ANOVA analysis of group mean scores showed significant differences among the 4 student groups in the active experimentation learning mode. Post hoc tests confirmed that Chilean students are less likely to be active learners than their teachers or Canadian students, a finding of significance in preparing students to assume self-direction of their learning. Canadian faculty had higher abstract conceptualization scores than Chilean faculty, which has implications for faculty development of educator roles for SDL/PBL.

Applying disease management strategies to Medicare.

Medicare coverage begins for many when they have already developed one or more chronic diseases, and it often pays for the latest and costliest phases. Population-based disease modeling, patient screening, and monitoring would be appropriate interventions for chronic renal disease. Patients who have not yet advanced to end-stage renal disease would benefit from management of diabetes and hypertension, avoidance of nephrotoxic substances, and better preparation for dialysis. Administrative support could take the form of clinical guidelines, physician-led multidisciplinary teams, integrated delivery systems, provider and patient education, and new information technologies. Medicare reflects the long-term public perspective, and thus should further this new direction by supporting education, reimbursing for prevention efforts and allied health services, encouraging efficiency, and monitoring cost and quality outcomes.

Recognizing and managing anemia.

Anemia is not an uncommon problem. Knowledge of a few common laboratory tests can be helpful when caring for patients with anemia. By reviewing approaches to classifying, evaluating, and managing patients with common anemias, nurses will be prepared to care for patients with an anemia more confidently.

Competence in discourse as a measure of social integration and quality of life in persons with traumatic brain injury.

Persisting difficulties in communication are a serious handicap faced by many after traumatic brain injury (TBI) and a major barrier to community reintegration. Conventional approaches to the study of communication problems after TBI have focused on the form of language production and expression, usually in terms of phonological, semantic, and syntactical features. Most TBI patients, however, perform overall within normal ranges on these conventional indicators. More recently, attention has focused on language in its naturally-occurring form, that is, discourse, which is heavily influenced by linguistic, cognitive and social skills. Because most TBI patients are left with residual deficits in these areas, study of discourse abilities seem to be particularly suited to understanding their problems in communication and facilitating eventual reintegration into the community. This study was designed to determine if and how the conversational discourse of TBI patients differs from a matched non-TBI group and whether any identified variables are related to measures of outcome as measured by community integration and quality of life. Additionally, the study was designed to explore the relationship between TBI and features of discourse across conversational, narrative, procedural genres. TBI patients (n = 30) from an out-patient brain injury programme were compared to matched controls (n = 10) in the three discourse genres. Bivariate and multivariate analyses evaluated 23 measures of discourse efficiency, complexity, topic management, information and pragmatic behaviours in each genre as well as measures of psychosocial adjustment, particularly social integration and quality of life. Results indicated that TBIs were significantly different from controls on several measures of discourse and psychosocial adjustment. A number of other features of discourse were found to correlate significantly with social integration and quality of life. Interestingly, discourse variables appeared to correlate with social integration more strongly than age, gender, education, and other conventional psychosocial factors. Contrary to prediction, features of conversational discourse did not correlate more strongly than other types of discourse with social integration and quality of life. Discussion centred on the apparent comorbidity of features in everyday discourse and psychosocial determinants that were associated with quality of life and social integration.

Functional outcome assessment of adults with right hemisphere brain damage.

This article addresses functional outcome assessment of adults with cognitive-communicative disorders due to relatively focal right hemisphere brain damage (RBD). Our discussion observes the World Health Organization's orientation on the multidimensional consequences of health conditions. The WHO framework distinguishes specific deficits (impairments) from their functional consequences: disabilities, or restrictions in daily life activities and handicaps, or broader changes in life role participation. Although there is little evidence about the functional aftermath of RBD, especially in relation to cognitive-communicative disorders, we summarize the data and observations that are available and hypothesize about relationships among outcomes at different levels. We also describe some tools and procedures that may be useful for measuring functional outcomes after RBD, along with relevant caveats, and end with a discussion of research needs and future directions, emphasizing gaps that span the range from basic investigation to treatment research to instrument and procedure development.

Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells.

Phosphatidic acid (PA) and diacylglycerol (DG) are lipids involved in signal transduction and in structural membrane-lipid biosynthesis in cells. Phosphatidic acid phosphatase (PAP) catalyzes the conversion of PA to DG. This enzyme exists in at least two isoforms, one of which (PAP1) is presumed to be cytosolic and membrane associated and the other (PAP2) to be an integral membrane protein. Homology search of the GenBank database using a murine sequence probe enabled the cloning of several putative human isoenzymes. Two isoforms, presumed to be alternative splice variants from a single gene, designated as PAP2-alpha1 and PAP2-alpha2, have been cloned and expressed. The PAP2-alpha1 and PAP2-alpha2 have a 84% and a 72% overall match, respectively, with the published mouse PAP amino acid sequence. The area of alternative exon usage was confined to the coding region at amino acids 20 to 70. Ectopic expression of PAP2-alpha1 and PAP2-alpha2 cDNAs in ECV304 endothelial cells led to a 6- to 8-fold and a 2-fold increase in PAP activity, respectively, in cell-free extracts using an in vitro assay that measured the conversion of [14C]PA to [14C]DG. The increase in PAP activity in PAP2-alpha-transfected cells correlated with a >50% decrease in the steady-state PA level. Northern analysis showed that PAP2-alpha mRNA expression was suppressed in several tumor tissues, notably those derived from the lower alimentary tract. Subsequent analysis of colon tumor tissue derived from four donors confirmed lower expression of PAP2-alpha than in matching normal colon tissue. Considering these data and previous demonstrations that certain transformed cell lines have lower PAP activity, we suggest that human PAP cDNAs may be candidates for gene therapy for certain tumors.

Biologic response modulation by tumor necrosis factor alpha (TNF alpha) in a phase Ib trial in cancer patients.

During a phase I study of recombinant human tumor necrosis factor (TNF) in cancer patients, serial immune studies were performed and analyzed for effects of TNF. The TNF (specific activity 9.6 x 10(6) U/mg protein, < 5.0 endotoxin units/mg protein) was given over 2 h intravenously on days 1, 8-12, 29-33, 50-54, and 71-75 at doses of 40, 80, 160, 200, and 240 micrograms/m2. Immunologic testing was performed before therapy three times and subsequently on days 2, 8, 10, 12, 29, 33, 50, 54, 71, 75, and off-study two times. Immune parameters evaluated included cytotoxicity [natural killer (NK), spontaneous lymphokine activated killer cells (LAK), LAK, and monocyte], cytokine production [spontaneous and stimulated interferon (IFN)-gamma and interleukin (IL)-2], superoxide production [resting and stimulated polymorphonuclear (PMN) and mononuclear cells (MNC)], and phenotype of peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD16, CD56, CD19). Data were analyzed for long-term effects, the effect after 1 day of treatment (day 1), and for weekly effect (change from day 1 to day 5 of a given treatment week). Significant decreases were seen in the spontaneous cytotoxicity of peripheral blood NK cells and IL-2-inducible LAK cells, whereas increases in spontaneous peripheral blood LAK activity were seen with TNF treatment. Consistent increases in superoxide production of resting PMN and MNC were demonstrated, with late increases in superoxide production by opsonized, zymosan-treated PMN. No spontaneous IFN-gamma or IL-2 were noted in sera with treatment, but production of IL-2 by MNCs rose with TNF treatment. During 5 days of TNF treatment, the percentages of circulating CD8+ and CD56+ cells decreased, whereas that of CD4+ and CD19+ cells increased significantly and consistently, as determined by a multivariate analysis. Significant changes in several independently measured parameters were observed, including a dose-related diminished production of IFN-gamma by MNC stimulated by phytohemagglutinin and increased in vitro-generated LAK activity. Because there was no clinical response in this trial, no association of immunologic change with clinical response can be made. No biologically optimal dose of TNF was evident. The data suggest that TNF may act as a trigger cytokine, initiating a broad immune/inflammatory response.

Assessment of depression in patients with brain pathology: the case of stroke.

The assessment of depression in patients with brain pathologies--a topic of considerable clinical and research interest--is complicated by a variety of factors. Among the most problematic are cognitive consequences of brain injury that can diminish the reliability and validity of information used to diagnose depression, determine its severity, ascertain its predictors, and evaluate its impact. In this article, the authors examine the challenges to depression assessment in patients who have had a stroke, the neurologically impaired population in which it has been most frequently studied. Focusing on poststroke depression research, they describe methodological limitations that may contribute to conflicting outcomes and conclusions and offer suggestions for improving the specificity, consistency, validity, and reliability of assessment methods and procedures when investigating depression in patients with brain pathologies.