Single cell analysis of cancer cells using an improved RT-MLPA method has potential for cancer diagnosis and monitoring.

Single cell analysis techniques have great potential in the cancer genomics field. The detection and characterization of circulating tumour cells are important for identifying metastatic disease at an early stage and monitoring it. This protocol is based on transcript profiling using Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (RT-MLPA), which is a specific method for simultaneous detection of multiple mRNA transcripts. Because of the small amount of (circulating) tumour cells, a pre-amplification reaction is performed after reverse transcription to generate a sufficient number of target molecules for the MLPA reaction. We designed a highly sensitive method for detecting and quantifying a panel of seven genes whose expression patterns are associated with breast cancer, and optimized the method for single cell analysis. For detection we used a fluorescence-dependent semi-quantitative method involving hybridization of unique barcodes to an array. We evaluated the method using three human breast cancer cell lines and identified specific gene expression profiles for each line. Furthermore, we applied the method to single cells and confirmed the heterogeneity of a cell population. Successful gene detection from cancer cells in human blood from metastatic breast cancer patients supports the use of RT-MLPA as a diagnostic tool for cancer genomics.

Pharmaceutical policies: effects of cap and co-payment on rational drug use.

BACKGROUND: Growing expenditures on prescription drugs represent a major challenge to many health systems. Cap and co-payment (direct cost-share) policies are intended as an incentive to deter unnecessary or marginal utilisation, and to reduce third-party payer expenditures by shifting parts of the financial burden from the insurer to patients, thus increasing their financial responsibility for prescription drugs. Direct patient drug payment policies include caps (maximum number of prescriptions or drugs that are reimbursed), fixed co-payments (patients pay a fixed amount per prescription or drug), coinsurance (patients pay a percent of the price), ceilings (patients pay the full price or part of the cost up to a ceiling, after which drugs are free or available at reduced cost), and tier co-payments (differential co-payments usually assigned to generic and brand drugs). OBJECTIVES: To determine the effects of cap and co-payment (cost-sharing) policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 6 September 07), Cochrane Central Register of Controlled Trials (27 August 07), MEDLINE (29 August 07), EMBASE (29 August 07), NHS EED (27 August 07), ISI Web of Science (09 January 07), CSA Worldwide Political Science Abstracts (21 October 03), EconLit (23 October 03), SIGLE (12 November 03), INRUD (21 November 03), PAIS International (23 March 04), International Political Science Abstracts (09 January 04), PubMed (25 February 04), NTIS (03 March 04), IPA (22 April 04), OECD Publications & Documents (30 August 05), SourceOECD (30 August 05), World Bank Documents & Reports (30 August 05), World Bank e-Library (04 May 05), JOLIS (22 February 06), Global Jolis (22 February 06), WHOLIS(22 February 06), WHO web site browsed (25 August 05). SELECTION CRITERIA: We defined policies in this review as laws, rules, or financial or administrative orders made by governments, non-government organisations or private insurers. We included randomised controlled trials, non-randomised controlled trials, interrupted time series analyses, repeated measures studies and controlled before-after studies of cap or co-payment policies for a large jurisdiction or system of care. To be included, a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes or costs (expenditures). DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study limitations. We undertook quantitative analysis of time series data for studies with sufficient data. MAIN RESULTS: We included 30 evaluations (in 21 studies). Of these, 11 evaluated fixed co-payment, six evaluated coinsurance with a ceiling, four evaluated caps, three evaluated fixed co-payment with a ceiling, three evaluated tier co-payment, one evaluated ceiling, one evaluated fixed co-payment and coinsurance with a ceiling, and one evaluated a fixed co-payment with a cap. Most of the included evaluations were observational studies and the quality of the evidence was found to be generally low to moderate. Introducing or increasing direct co-payments reduced drug use and saved plan drug expenditures across studies. Patients responded through drug discontinuation or by cost-sharing. Investigators found reductions for life-sustaining drugs or drugs that are important in treating chronic conditions as well as other drugs. Few studies reported on the effects on health and healthcare utilisation. One study found adverse effects on health through increased healthcare utilisation when a cap was introduced in a vulnerable population. No statistically significant change in use of healthcare services was found in other studies when a cap was introduced on a drug considered over-prescribed in a vulnerable population, or following a shift from a two-tier to a three-tier system with increased co-payments for tier-1 drugs in a general population. AUTHORS' CONCLUSIONS: We found a diversity of cap and co-payment policies. Poor reporting of the intensity of interventions and differences in setting, populations and interventions made it difficult to make comparisons across studies. Cap and co-payment polices can reduce drug use and save plan drug expenditures. However, although insufficient data on health outcomes were available, substantial reductions in the use of life-sustaining drugs or drugs that are important in treating chronic conditions may have adverse effects on health, and as a result increase the use of healthcare services and overall expenditures. Direct payments are less likely to cause harm if only non-essential drugs are included or exemptions are built in to ensure that patients receive needed medical care.

Pharmaceutical policies: effects of financial incentives for prescribers.

BACKGROUND: Pharmaceuticals, while central to medical therapy, pose a significant burden to health care budgets. Therefore regulations to control prescribing costs and improve quality of care are implemented increasingly. These include the use of financial incentives for prescribers, namely increased financial accountability using budgets and performance based payments. OBJECTIVES: To determine the effects on drug use, healthcare utilisation, health outcomes and costs (expenditures) of policies, that intend to affect prescribers by means of financial incentives. SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (August 2003), Cochrane Central Register of Controlled Trials (October 2003), MEDLINE (October 2005), EMBASE (October 2005), and other databases. SELECTION CRITERIA: Policies were defined as laws, rules, financial and administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug use, healthcare utilisation, health outcomes, and costs. The study had to be a randomised or non-randomised controlled trial, interrupted time series analysis, repeated measures study or controlled before-after study evaluating financial incentives for prescribers introduced for a jurisdiction or healthcare system. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study limitations. MAIN RESULTS: Thirteen evaluations of budgetary policies and none of performance based payments met our inclusion criteria. Ten studies evaluated general practice fundholding in the UK, one the Irish Indicative Drug Target Savings Scheme (IDTSS) and two evaluated German drug budgets for physicians in private practice. The interrupted time series analyses had some limitations. All the controlled before-after studies (all from the UK) had serious limitations. Drug expenditure (per item and per patient) and prescribed drug volume decreased with budgets in all three countries. Evidence indicated increased use of generic drugs in the UK and Ireland, but was inconclusive on the use of new and expensive drugs. We found no clear evidence of increased health care utilisation and no studies reporting effects on health. Administration costs were not reported. No studies on the effects of performance-based payments or other policies met our inclusion criteria. AUTHORS' CONCLUSIONS: Based on the evidence in this review from three Western European countries, drug budgets for physicians in private practice can limit drug expenditure by limiting the volume of prescribed drugs, increasing the use of generic drugs or both. Since the majority of studies included were found to have serious limitations, these results should be interpreted with care.

Pharmaceutical policies: effects of reference pricing, other pricing, and purchasing policies.

BACKGROUND: Pharmaceuticals can be important for people's health. At the same time drugs are major components of health care costs. Pharmaceutical pricing and purchasing policies are used to determine or affect the prices that are paid for drugs. Examples are price controls, maximum prices, price negotiations, reference pricing, index pricing and volume-based pricing policies. The essence of reference pricing is to establish a maximum level of reimbursement for a group of drugs assumed to be therapeutically equivalent. OBJECTIVES: To determine the effects of pharmaceutical pricing and purchasing policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 22/08/03), Cochrane Central Register of Controlled Trials (15/10/03), MEDLINE (07/09/05), EMBASE (07/09/05), ISI Web of Science (08/09/05), CSA Worldwide Political Science Abstracts (21/10/03), EconLit (23/10/03), SIGLE (12/11/03), INRUD (21/11/03), PAIS International (23/03/04), International Political Science Abstracts (09/01/04), NHS EED (20/02/04), PubMed (25/02/04), NTIS (03/03/04), IPA (22/04/04), OECD Publications & Documents (30/08/05), SourceOECD (30/08/05), World Bank Documents & Reports (30/08/05), World Bank e-Library (04/05/05), JOLIS (22/08/05), Global Jolis (22/08/05 and 23/08/05), WHOLIS (29/08/05). SELECTION CRITERIA: Policies in this review were defined as laws, rules, financial and administrative orders made by governments, non-government organisations or private insurers. To be included a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes, and costs (expenditures); the study must be a randomised controlled trial, non-randomised controlled trial, interrupted time series analysis, repeated measures study or controlled before-after study of a pharmaceutical pricing or purchasing policy for a large jurisdiction or system of care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study limitations. Quantitative analysis of time series data, for studies with sufficient data, and qualitative analyses were undertaken. MAIN RESULTS: We included 10 studies of reference pricing and one study of index pricing. Most of the reference pricing studies were for senior citizens in British Columbia, Canada. The use (dispensing) of reference drugs increased in five studies, between 60% and 196% immediately after introduction of reference drug pricing, whereas the use of cost sharing drugs decreased by between 19% and 42% in four studies. In three studies the reference drug group expenditures decreased (range 19% - 50%), whereas in the fourth study the expenditures increased by 5% in the short term. The results after six months of reference pricing do not show any clear pattern in relationship to the immediate effects. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. For index pricing the evidence was much more limited than for reference drug pricing. A small reduction in drug prices was found. AUTHORS' CONCLUSIONS: We found relatively few studies of pricing policies. The majority of the studies dealt with reference pricing. They had few methodological limitations. Based on the evidence in this review, mostly from senior citizens in British Columbia, Canada, reference drug pricing can reduce third party drug expenditures by inducing a shift in drug use towards less expensive drugs. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. The analysis and reporting of the effects on patient drug expenditures were limited in the included studies and administration costs were not reported.

[Elective surgery--cancellations, ring fencing and efficiency]. / Elektiv kirurgi--strykninger, skjerming og effektivitet.

BACKGROUND: We set out to study to what extent emergency admissions disturb elective surgical activities, resulting in decreasing efficiency and fewer elective procedures. We looked at the evidence of whether ring fencing elective surgery is an effective strategy to reduce disturbance from emergency activities, and improve the overall efficiency in hospitals with emergency as well as elective activities. MATERIAL AND METHODS: We systematically searched for published studies that have addressed the above mentioned issues. RESULTS: Approximately 10-17% of elective surgical operations are cancelled. In a Norwegian study, about 14% of cancellations seem to be caused by interference from emergency admissions. We did not find any empirical evidence on the effects of ring fencing elective surgery. INTERPRETATION: The belief that ring fencing is an effective strategy to decrease cancellations and increase hospital efficiency seems to be anchored in a priori reasoning rather than in published evidence.

[Observational units--same good service to lower costs?]. / Observasjonsposter--like godt tilbud til lavere kostnader?

BACKGROUND: With increased demand for hospital services and limited resources in the health sector, modes of organisation of services which give the same health outcome, but at lower cost, are of interest. Observation units in hospitals imply rapid diagnostic procedures and/or brief, but adequate treatment. We looked at the evidence for whether stays in observational units provide similar health outcome and reduce the admissions costs for hospitals compared to standard inpatient stays. MATERIAL AND METHODS: We systematically evaluated four randomized controlled studies that have compared the outcome for chest pain and asthma patients admitted to either observational units or directly to ordinary hospital units. The outcomes in focus were health effects measured as mortality and/or complications, length of stay and direct hospital costs. RESULTS: The studies indicate that for the conditions included, there are no health outcome differences between patients treated in observational units on one hand or in ordinary hospital units on the other. Stays in observational units do not seem to imply increased risk of complication. Furthermore, the studies show a reduction in length of stay and hospital costs associated with the use of observational units. INTERPRETATION: The main reason for the reduction in length of stay and cost is quicker diagnosis in observational units than in the ordinary hospital units. The preconditions for these results are clear by defined criteria for selection of patients to the different units and well-defined protocols for making diagnoses and treating patients. If many patients after staying in observational units are transferred to ordinary hospital units or are discharged and then readmitted, the economic benefits of observational units could be undermined.