Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research.

Liver disease represents an increasing cause of global morbidity and mortality. Currently, liver transplant is the only treatment curative for end-stage liver disease. Donor organs cannot meet the demand and therefore scalable treatments and new disease models are required to improve clinical intervention. Pluripotent stem cells represent a renewable source of human tissue. Recent advances in three-dimensional cell culture have provided the field with more complex systems that better mimic liver physiology and function. Despite these improvements, current cell-based models are variable in performance and expensive to manufacture at scale. This is due, in part, to the use of poorly defined or cross-species materials within the process, severely affecting technology translation. To address this issue, we have developed an automated and economical platform to produce liver tissue at scale for modelling disease and small molecule screening. Stem cell derived liver spheres were formed by combining hepatic progenitors with endothelial cells and stellate cells, in the ratios found within the liver. The resulting tissue permitted the study of human liver biology 'in the dish' and could be scaled for screening. In summary, we have developed an automated differentiation system that permits reliable self-assembly of human liver tissue for biomedical application. Going forward we believe that this technology will not only serve as anin vitroresource, and may have an important role to play in supporting failing liver function in humans.

The Jamaican Haemophilia Registry: Describing the burden of disease.

INTRODUCTION: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. AIM: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. METHODS: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. RESULTS: In all, 45 PWH were registered (mean age: 29, range: 0.17-69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores - mean Haemo-QoL-A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. CONCLUSIONS: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.

[The way from cost approval to bariatric surgery : Analysis of resource utilization in a maximum care hospital]. / Vom Antrag auf Kostengutsprache bis zur bariatrischen Operation : Personelle Ressourcenanalyse an einem Zentrum der Maximalversorgung.

BACKGROUND: Morbid obesity is a medical and economic challenge. Patients who have the indications for bariatric surgery face a long way from the first visit until surgery and a high utilization of resources is required. OBJECTIVES: The present study aimed to evaluate labor costs and labor time required to supervise obese patients from their first visit until preparation of a bariatric report to ask for cost acceptance of bariatric surgery from their health insurance. In addition, the reasons for not receiving bariatric surgery after receiving cost acceptance from the health insurance were evaluated. MATERIAL AND METHODS: Patients who had indications for bariatric surgery according to the S3 guidelines between 2012 and 2013, were evaluated regarding labor costs and labor time of the process from the first visit until receiving cost acceptance from their health insurance. Furthermore, body mass index (BMI), age, sex, Edmonton Obesity Staging System (EOSS) stage and comorbidities were evaluated. Patients who had not received surgery up to December 2015 were contacted via telephone to ask for the reasons. RESULTS: In the present study 176 patients were evaluated (110 females, 62.5%). Until preparation of a bariatric report the patients required an average of 2.7 combined visits in the department of surgery with the department of nutrition, 1.7 visits in the department of psychosomatic medicine, 1.5 separate visits in the department of nutrition and 1.4 visits in the department of internal medicine. Average labor costs from the first visit until the bariatric survey were 404.90 ± 117.00 euros and 130 out of 176 bariatric reports were accepted by the health insurance (73.8%). For another 40 patients a second bariatric survey was made and 20 of these (50%) were accepted, which results in a total acceptance rate of 85.2% (150 out of 176). After a mean follow-up of 2.8 ± 1.1 years only 93 out of 176 patients had received bariatric surgery (53.8%). Of these 16 had received acceptance of surgery by their health insurance only after a second bariatric survey. CONCLUSION: A large amount of labor and financial resources are required for treatment of obese patients from first presentation up to bariatric surgery. The cost-benefit calculation of an obesity center needs to include that approximately one half of the patients do not receive surgery within more than 2.5 years.

[Cost-Effectiveness of the 21 Gene Assay in Patients with Node-Positive Breast Cancer]. / Wirtschaftlichkeit des 21 Gene Tests in der Behandlung von Patientinnen mit nodal-positivem Mammakarzinom.

Aim: Breast cancer is the most common type of cancer for women. Most guidelines recommend patients with lymph-node positive (LN+) early stage breast cancer to undergo adjuvant chemotherapy to prevent or delay distant recurrence. This may lead to frequent, general usage of chemotherapy accompanied with high costs and side effects. The Oncotype DX, also called 21 Gene Assay, by Genomic Health is a genomic test which predicts the individual risk of breast cancer recurrence as well as the benefits of chemotherapy. Economic analyses have indicated the cost-effectiveness of the 21 Gene Assay for patients with LN- breast cancer. This paper discusses recent research on the cost-effectiveness of using this assay for patients with LN+ breast cancer. Methods: A systematic literature research was undertaken using the following databases: Pubmed, Embase, Business Source Complete and EconLit. Studies found were analysed for study design, parameters, and analysis of uncertainty. The transferability of the results to Germany was examined using a list of criteria. Results: 7 relevant economic analyses were identified. Incremental cost-utility ratios ranged from cost-savings of € 3 548 per patient to additional costs of € 9 113 per QALY gained. The transferability of the results to Germany is limited particularly by differences in the medical cost approach, in absolute and relative prices in health-care, and by practice variation. Conclusion: There is evidence that the cost-utility of the assay when used for LN+ breast cancer is basically comparable to that for the use with the LN- type. More precise results for Germany would require valid data on the risk of recurrence as well as on the description and evaluation of health-related quality of life of patients.

[Challenges in building a surgical obesity center]. / Herausforderungen beim Aufbau eines operativen Adipositaszentrums.

BACKGROUND: It is estimated that approximately 1 million adults in Germany suffer from grade III obesity. The aim of this article is to describe the challenges faced when constructing an operative obesity center. METHODS: The inflow of patients as well as personnel and infrastructure of the interdisciplinary Diabetes and Obesity Center in Heidelberg were analyzed. The distribution of continuous data was described by mean values and standard deviation and analyzed using variance analysis. RESULTS: The interdisciplinary Diabetes and Obesity Center in Heidelberg was founded in 2006 and offers conservative therapeutic treatment and all currently available operative procedures. For every operative intervention carried out an average of 1.7 expert reports and 0.3 counter expertises were necessary. The time period from the initial presentation of patients in the department of surgery to an operation was on average 12.8 months (standard deviation SD ± 4.5 months). The 47 patients for whom remuneration for treatment was initially refused had an average body mass index (BMI) of 49.2 kg/m(2) and of these 39 had at least the necessity for treatment of a comorbidity. Of the 45 patients for whom the reason for the refusal of treatment costs was given as a lack of conservative treatment, 30 had undertaken a medically supervised attempt at losing weight over at least 6 months. Additionally, 19 of these patients could document participation in a course at a rehabilitation center, a Xenical® or Reduktil® therapy or had undertaken the Optifast® program. For the 20 patients who supposedly lacked a psychosomatic evaluation, an adequate psychosomatic evaluation was carried out in all cases. CONCLUSIONS: The establishment of an operative obesity center can last for several years. A essential prerequisite for success seems to be the constructive and targeted cooperation with the health insurance companies.

Status of robotic assistance--a less traumatic and more accurate minimally invasive surgery?

PURPOSE: Robotic assistance is considered one innovation within abdominal surgery over the past decade that has the potential to compensate for the drawbacks of conventional laparoscopy, such as limited degree of freedom, 2D vision, fulcrum, and pivoting effect. Robotic systems provide corresponding solutions as 3D view, intuitive motion and enable additional degrees of freedom. This review provides an overview of the history of medical robotics, experimental studies, clinical state-of-the-art and economic impact. METHODS: The Medline database was searched for the terms "robot, telemanipulat, and laparoscop." A total of 2,573 references were found. All references were considered for information on robotic assistance in advanced laparoscopy. Further references were obtained through cross-referencing the bibliography cited in each work. RESULTS: In experimental studies, current robotic systems showed superior handling and ergonomics compared to conventional laparoscopic techniques. In gynecology especially for hysterectomy and in urology especially for prostatectomy, two procedures formerly performed via an open approach, the robot enables a laparoscopic approach. This results in reduced need for pain medication, less blood loss, and shorter hospital stay. Within abdominal surgery, clinical studies were generally unable to prove a benefit of the robot. While the benefit still remains open to discussion, robotic systems are spreading and are available worldwide in tertiary centers. CONCLUSION: Robotic assistance will remain an intensively discussed subject since clinical benefits for most procedures have not yet been proven. The most promising procedures are those in which the robot enables a laparoscopic approach where open surgery is usually required.

[Evaluation of potential liver living donors. Logistic and financial aspects]. / Evaluation potenzieller Leberlebendspender. Logistik und finanzieller Rahmen.

INTRODUCTION: The increasing shortage of cadaveric organs makes living-related liver transplantation a more and more important option. Safety for the donor has the highest priority, and therefore detailed and thorough evaluation is needed. MATERIALS AND METHODS: All potential donors who had been evaluated at our center from January 2001 to March 2002 ( n=100) were included in a retrospective study to analyse the qualitative, logistical, and economic aspects of the evaluation. RESULTS: Seventy-three percent of the potential donors were found to be unsuitable for living donation during the evaluation process. The main reasons were: uncompatible blood group, availability of cadaveric transplant by Eurotransplant, steatosis of more than 10% of hepatocytes in liver biopsy, insufficient liver volume, and psychosocial reasons. The expenditure for all scheduled investigations was 4,469 euro for a complete evaluation. CONCLUSION: While on the one hand, high standards of the evaluation process must be guaranteed, insufficient reimbursement on the other should not lead centers to reduce either quantity or quality of necessary examinations entered in the evaluation protocol.

Assessment of the clinical and virological protection provided by a commercial inactivated bovine viral diarrhoea virus genotype 1 vaccine against a BVDV genotype 2 challenge.

A new genotype of bovine viral diarrhoea virus (BVDV), designated BVDV-2, has emerged in the last decade and in recent years the prevalence of BVDV-2 strains has increased. A vaccination-challenge study was carried out to determine the cross-protective efficacy of a commercial inactivated vaccine containing a BVDV-1 strain. A group of five BVDV-free calves was vaccinated twice and a second group of five calves served as negative controls. Two months after the first vaccination, all the calves were challenged intranasally with BVDV-2 strain BVD890. The clinical signs of disease, the changes in haematological variables and the level of viraemia were significantly less in the vaccinated group.

What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting?

OBJECTIVE: To assess whether osteoporosis education, with and without bone mineral density (BMD) testing, increases the initiation of lifestyle changes and pharmaceutical treatment to prevent osteoporosis. DESIGN: A total of 508 women, aged 54-65, from a large managed care organization who were not on osteoporosis prevention therapy participated in an intervention study. Participants were randomly assigned to either an education class on osteoporosis (n = 301) or education plus BMD (n = 207). A control group of 187 women receiving no intervention were also surveyed to serve as comparison. Group differences and differences based on BMD test result were compared 6 months after education regarding self-reported changes in health behaviors using chi2 tests and logistic regression analyses. RESULTS: Of the 508 intervention participants, 455 (90%) responded to the follow-up survey. Initiation of hormone replacement therapy was reported by 9%, with 5% reporting starting alendronate. More than half reported changes in diet, exercise, or calcium intake. Forty-three percent increased their vitamin D intake. There were no significant group differences in behavior except with regard to pharmaceutical therapy; subjects with education plus BMD were three times more likely than those receiving education only to report starting hormone replacement therapy (p = 0.004). Low BMD scores were associated with increasing vitamin D intake (p = 0.03) and starting medication (p = 0.001). Women in the intervention groups were significantly more likely to report modifying their diet (p < 0.001), calcium (p < 0.01), and vitamin D intake (p < 0.0001) than women in the control group, not exposed to education. CONCLUSION: Education regarding osteoporosis prevention seems to encourage women to make lifestyle changes. The inclusion of BMD testing enhances the likelihood that women will consider pharmaceutical therapy.

Screening for hepatitis C virus in a health maintenance organization.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major public health problem and is associated with over 10,000 deaths a year in the United States. In its early stages, HCV tends to be asymptomatic and can be detected only through screening. OBJECTIVES: To develop and validate a database risk algorithm for HCV infection using electronic data at HealthPartners, a health maintenance organization (HMO) in Minnesota. A secondary objective was to evaluate the benefit of screening health care workers for HCV. METHODS: A database risk algorithm was developed using diagnostic and procedure codes in the administrative database to identify at-risk enrollees. One thousand three hundred eighty enrollees (an at-risk sample and a control sample) and 502 health care workers participated in anonymous screening. Both descriptive statistics and logistic regression were used to examine the frequency of HCV infection, associations with risk factors, self-selection factors in participation, and concordance between the database risk algorithm and the risk profile questionnaire. RESULTS: Eleven enrollees tested positive for HCV, 9 from the at-risk sample and 2 from the control sample. All health care workers tested negative for HCV. Both lifestyle and medical risk factors were associated with positive test results for HCV. Enrollees with alcohol-drug diagnoses were less likely to participate in screening. A substantial proportion of enrollees with risk factors was identified either by the database risk algorithm or the risk profile questionnaire, but not by both. CONCLUSION: While the frequency of HCV infection was lower than previous estimates for the US population, the strong correlation with risk factors suggests that using the database risk algorithm for screening is a useful approach. Managed care plans with suitable data on their enrollee populations are in a key position to serve an important public health role in detecting asymptomatic patients who are infected with HCV.

Pharmaceutical care for patients with chronic conditions.

OBJECTIVE: To assess factors associated with participation in pharmaceutical care and the benefits of participation--in terms of amount of information about medications, administration of medications, and awareness of side effects. DESIGN: Quasi-experimental design, with a control group. Medication Survey, administered 6 months after pharmaceutical care intervention to participants, refusers, and controls. Logistic regression analyses. SETTING: Three staff clinic pharmacies and three contract clinic pharmacies affiliated with a health maintenance organization (HMO). PATIENTS AND OTHER PARTICIPANTS: Patients with chronic health conditions (asthma, chronic obstructive pulmonary disease, or heart disease) enrolled at six intervention sites, identified through the HMO's electronic pharmacy database. Control sample with the same chronic health conditions, without access to pharmaceutical care (n = 210 participants, 162 refusers, and 368 controls; overall adjusted response rate = 72%). INTERVENTION: Pharmaceutical care, in the form of a comprehensive drug therapy management program. MAIN OUTCOME MEASURES: Predictors of participation, amount of information about medications, use of reminder methods, and awareness of side effects. RESULTS: The following variables were significantly associated with the probability of participating in pharmaceutical care (P < .05): number of medications, employment, income, health status, education, and living situation. Participants were more likely than controls to say they received "a lot of information" from their pharmacist about all aspects of medications (odds ratio [OR], 1.75 to 2.68). Participants were more likely to report leaving their medication container in a visible place and using two or more reminder methods (OR, 1.87 to 1.48). There were no significant differences in the probability of missing doses. Participants were more likely to report experiencing "symptoms or problems" associated with prescription medications (OR, 1.81). CONCLUSION: Pharmaceutical care appears to increase the information given to patients about medications, promote more effective self-administration of medications by encouraging patients to use systematic reminders, and increase awareness of medication side effects.

Educating health professionals: a hepatitis C educational program in a health maintenance organization.

OBJECTIVE: To describe the components of and staff reaction to an educational outreach program about hepatitis C (HCV) at a managed care organization in Minnesota. PROJECT PROTOCOL: Educational programs for primary care clinicians consisted of lunch-and-learn sessions conducted in 2 phases. In phase 1 (1997-1998), educational programs were offered in 4 clinics; in phase 2 (1999), these programs were offered to a larger number of clinics. There was a structured, 2-stage recruitment process, and the protocol included multiple contacts that involved sending educational materials to participants several weeks before the program. A development team, comprised of key health maintenance organization (HMO) stakeholders, provided consultation. EVALUATION: The initiative reached more than 1000 healthcare professionals, including 150 physicians. The educational programs received very high ratings, and pre- and posttests documented significant improvement in knowledge about HCV. CONCLUSIONS: This successful educational initiative had 5 key elements: (1) value to healthcare staff (i.e., importance of the topic and quality of the programs); (2) incentives (i.e., convenience, free lunch, and continuing medical education/continuing education unit credits); (3) repeated exposures (i.e., multiple opportunities for learning, both oral and written); (4) commitment by key stakeholders at the HMO and the clinics; and (5) an exceptionally well-organized implementation plan.

Statistical adequacy of the Abel Assessment for Interest in Paraphilias.

A review of the psychometric properties of the Abel Assessment for Interest in Paraphilias (AAIP) is presented. The data supporting the AAIP's history, purpose, data, reliability, validity, and norms are reported, with the conclusion that its use with adults is tenuous at best and its use with adolescents is as yet unsupported. Pragmatic concerns are noted, along with recommendations for further research.

Assessment of juvenile sexual offenders: reliability and validity of the Abel Assessment for Interest in Paraphilias.

Empirical tests of the reliability and validity of the Abel Assessment for Interest in Paraphilias (AAIP) as used with juvenile sexual offenders were performed. Test-retest reliability, screening validity, and diagnostic validity were assessed using several analytical approaches. The temporal stability, sensitivity, and specificity of the AAIP as used with adolescents in residential and day treatment were not demonstrated. The results indicate the need for further refinement of the AAIP.

S/HMO versus TEFRA HMO enrollees: analysis of expenditures.

This study compares expenditures on health care services for enrollees in a social health maintenance organization (S/HMO) and a Tax Equity and Fiscal Responsibility Act of 1982 (TEFRA)-risk Medicare health maintenance organization (HMO). In addition to the traditional Medicare services covered by the TEFRA HMO, the S/HMO provided a long-term care (LTC) benefit and case management services for chronic illness. There do not appear to be any overall savings associated with S/HMO membership, including any savings from substitution of S/HMO-specific services for other, traditional services covered by both the S/HMO and the TEFRA HMO.

The Pregnancy Risk Assessment Monitoring System (PRAMS): methods and 1996 response rates from 11 states.

OBJECTIVES: To determine if the Pregnancy Risk Assessment Monitoring System (PRAMS) is a unique and valuable MCH data source and an effective mechanism for states to collect MCH data, and to assess if recent changes in it have improved efficiency and flexibility. METHODS: Each component of the PRAMS methodology is described: sampling and stratification, data collection, questionnaire, and data management and weighting. To assess effectiveness, we calculated response rates, contact rates, cooperation rates, refusal rates, and questionnaire completion rates. Logistic regression was used to examine the relationship between maternal and infant characteristics and the likelihood of response. Four criteria were defined to measure improvement in PRAMS functioning. RESULTS: Overall response rates for the 11 states in 1996 ranged from 66% to 80%. Cooperation rates were high (85-99%), with contact rates somewhat lower (73-87%). Response rates were higher for women who were older, White, married, had more education, were first-time mothers, and had a normal-birthweight infant. In all states, parity and education were the most consistent predictors of response, followed by marital status and race. Between 1988-1990 and 1996-1999, the number of states and areas participating in PRAMS increased from 6 to 23, response rates improved, and the time for a state to start data collection and to obtain a weighted dataset both decreased. CONCLUSIONS: PRAMS is a unique and valuable MCH data source. The mail/telephone methodology used in PRAMS is an effective means of reaching most women who have recently given birth in the 11 states examined; however, some population subgroups are not reached as well as others. The system has become more efficient and flexible over time and more states now participate.

Quality improvement in primary care clinics.

BACKGROUND: Case studies from Project IMPROVE, the first randomized controlled trial to evaluate the effectiveness of continuous quality improvement (CQI) in primary care, were subjected to a qualitative analysis. Three questions were addressed: How does change in the health care environment affect a quality improvement (QI) process? How does clinic organization influence a QI process? and What is the impact of a QI process on clinic organization? METHOD: Case studies were conducted in 6 clinics that had been randomly selected from the 22 clinics participating in the IMPROVE intervention. The case study data consisted of observations of CQI team meetings, open-ended interviews with 30 informants (team members plus others in the clinics), interviews with IMPROVE consultants, and documentation from the project. The data were analyzed to identify themes and generate concepts, assess and compare the informants' experiences, and develop a conceptual framework stimulated by research and theory literature. RESULTS: Change and uncertainty in the health care environment both complicated the QI process and motivated participation in improvement. The smaller clinics appeared to have more difficulty with the QI process because of limited resources and lack of compatibility between the QI approach and their clinic organization. Project IMPROVE had two qualitative effects on clinics: increased awareness of preventive services and application of the CQI method to other problems and issues. CONCLUSION: QI initiatives can help clinics adapt to a changing health care environment and create functioning teams or groups that can address a variety of organization problems and tasks. The process should be flexible to accommodate varying organization structures and cultures.

The closing of a social HMO: a case study.

A social health maintenance organization (SHMO) integrates acute and long-term care and provides an extended-care benefit for elderly who are at risk of institutionalization. This article reports findings from a case study of the termination of the Group Health SHMO in Minnesota. Interviews were conducted with social workers and at-risk elderly who had been receiving long-term care through the SHMO. The case study examines the post-SHMO transition and the process of replacing SHMO care coordination and longterm care services. Most of the elderly and their caregivers indicated they were "losing ground"--that is, they were paying more or getting less care. Some were paying more for less care. Because they tended to switch to private-pay arrangements and to rely more on informal care, it appears that their care system became much less stable after the closing of the SHMO.