Economic evaluation of DNA ploidy analysis vs liquid-based cytology for cervical screening.

BACKGROUND: DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening. METHODS: A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear. CONCLUSION: Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.

Real-time data acquisition and alerts may reduce reaction time and improve perfusionist performance during cardiopulmonary bypass.

Delayed perfusionist identification and reaction to abnormal clinical situations has been reported to contribute to increased mortality and morbidity. The use of automated data acquisition and compliance safety alerts has been widely accepted in many industries and its use may improve operator performance. A study was conducted to evaluate the reaction time of perfusionists with and without the use of compliance alert. A compliance alert is a computer-generated pop-up banner on a pump-mounted computer screen to notify the user of clinical parameters outside of a predetermined range. A proctor monitored and recorded the time from an alert until the perfusionist recognized the parameter was outside the desired range. Group one included 10 cases utilizing compliance alerts. Group 2 included 10 cases with the primary perfusionist blinded to the compliance alerts. In Group 1, 97 compliance alerts were identified and, in group two, 86 alerts were identified. The average reaction time in the group using compliance alerts was 3.6 seconds. The average reaction time in the group not using the alerts was nearly ten times longer than the group using computer-assisted, real-time data feedback. Some believe that real-time computer data acquisition and feedback improves perfusionist performance and may allow clinicians to identify and rectify potentially dangerous situations.

Case report: Remote monitoring using Spectrum Medical Live Vue allows improved response time and improved quality of care for patients on cardiopulmonary support.

Clinician rounding on bedside extracorporeal membrane oxygenation (ECMO) is a common coverage practice at many centers across the USA. Occasionally, clinical issues or concerns may go unnoticed for a considerable period of time during the intervals of clinician rounds. We report a case utilizing the LiveVue (Spectrum Medical, Fort Mill, SC) remote monitoring for care of a patient on ECMO. A patient was placed on veno-arterial (VA) ECMO in our intensive care unit, using a Rotaflow centrifugal pump and a Quadrox D polymethylpentene (PMP) fiber oxygenator (both Maquet, Fairfield, NJ). Following ECMO initiation and stabilization, a two-hour rounding schedule was established for the covering perfusionist. On day two, shortly after the perfusionist had rounded, the ECMO flow began fluctuating between 0.1 and 2.1 L/min. A compliance alert (i.e. red flashing notification) was recognized by the perfusion team on a large screen monitor installed in the perfusion pump room. Immediate response from the perfusion team identified venous inflow obstruction due to cannula malposition. The pump revolutions per minute (rpm) and, thus, the resulting flow were temporarily reduced to prevent vessel intimal damage and the surgical team was summoned to reposition the venous cannula. Later in that ECMO run, a steady rise in pre-oxygenator pressure was noted by the perfusionist. This increasingly concerning event was able to be trended and monitored with the LiveVue from a remote location. After a few hours, a compliance alert was noticed again on the LiveVue screen in the pump room. The pre-oxygenator pressure increased by 150 mmHg and the circuit flow decreased by half. Again, the perfusionist response was immediate and an oxygenator change-out ensued. Once more, a potentially dangerous clinical scenario was avoided with continuous critical parameter remote monitoring using the LiveVue system.

Managing the extracorporeal membrane oxygenation (ECMO) circuit integrity and safety utilizing the perfusionist as the "ECMO Specialist".

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal technique of providing both cardiac and respiratory support to patients whose heart and lungs are so severely diseased or damaged that they can no longer serve their function. Neonatal and pediatric ECMO was accepted as practice in the early 1990s and according to the Extracorporeal Life Support Organization, ELSO; of the >50,000 patients registered, 73% have survived extracorporeal life support (ECLS). It is not uncommon to find initial cannulation of a patient receiving ECMO performed by a surgeon and then the maintenance of the patient being left in the hands of various others deemed as the "ECMO Specialists". The specialist has a broad base of professionals, including: nurses, respiratory therapists, perfusionists and physicians. Each institution, having its own unique training for these individuals, has provided a milieu for education, but does not share an established standard of care. From 2009, after the surge of the H1N1 epidemic, adult ECMO has been increasing; n=53 in 2010 to n=110 in 2012 at our institution. The perfusionist has been the "specialist" for ECMO at our institution since the early 1990s and remained at bedside during ECMO. We have now developed a safe circuit and fiscally responsible staffing model that utilizes a perfusionist and a telemetry-based electronic record keeper, permitting the perfusionist to leave the bedside and interact with the circuit when necessary. This has permitted an expansive growth of ECMO in our intensive care units at our facility incorporating a multidisciplinary collaboration system wide.

Respiratory failure of two sp gastric bypass patients and subsequent rescue with extracorporeal membrane oxygenation.

Severe obesity is a chronic condition that is difficult to treat through diet and exercise alone. Gastrointestinal surgery for obesity (bariatric surgery) alters the digestive process by either restrictive surgical alterations or malabsorptive operations. Some 10-20% of patients who have weight-loss surgery require follow-up operations to correct complications. Hypoxemia after gastric bypass surgery for morbid obesity, a reported complication, can occur as early as 24 h post surgery. Two patients presented with severe hypoxia and were placed on veno-venous extracorporeal membrane oxygenation (ECMO). Patient No. 1 had an obstruction of the alimentary limb of the gastric bypass due to suture adhesions, and patient No. 2 had an incarcerated diaphragmatic hernia. While on ECMO, ventilation using a protective strategy (60% FiO2, pressure-controlled ventilation inspiratory pressure (PCV) IP 25-27, positive end-expiratory pressure (PEEP) 10-14, permissive hypercapnia) was employed. An inflow cannula to the level of the right atrium served as arterial outflow from the circuit to the patient, while the femoral vein served as venous inflow to the ECMO circuit. Although ECMO in adult respiratory failure is often used as the last resort due to serious associated adverse events, we report two patients with life-threatening complications from gastric bypass who were rescued, resuscitated to day 7, and uneventfully discharged from the hospital to home.

Validation of egg yolk antibody testing as a method to determine influenza status in white leghorn hens.

Determination of the avian influenza (AI) status of a flock has traditionally been done by detection of serum antibodies. However, for many diseases, detection of antibodies in egg yolk has been effective in monitoring the disease status of laying flocks. This study compared the utility of egg yolk vs. serum for determining AI status in laying hen flocks. Specific-pathogen-free white leghorn hens were inoculated via the respiratory tract with a low-pathogenic H7N2 AI virus or sterile allantoic fluid or subcutaneously with an inactivated oil emulsion vaccine produced from the same AI virus or normal allantoic fluid. Antibody levels were determined by the agar gel immunodiffusion (AGID) test, the hemagglutination-inhibition (HI) test, and the enzyme-linked immunosorbent assay (ELISA). Anti-influenza antibodies were detected in sera of all live virus-inoculated hens by day 7 postinoculation (PI) (AGID and ELISA tests), but detection of antibodies in egg yolk was delayed by a few days, with all being positive by day 14 PI. Sera from all vaccinated hens were positive by day 14 PI (AGID and ELISA tests), and egg yolk was positive by day 18 PI. The HI test was less sensitive than the ELISA and AGID tests in detecting anti-influenza antibodies in both sera and yolk. Serum and yolk from all control birds remained negative throughout the study. These studies show that currently used serologic tests can detect antibodies in serum and yolk samples from hens exposed to live AI virus or from those that have been vaccinated. Antibody is detected earlier in the serum than in the yolk and antibody is detected earlier from birds exposed to a live infection compared to birds vaccinated with an inactivated oil emulsion vaccine.

Fatal encephalitis and myocarditis in young domestic geese (Anser anser domesticus) caused by West Nile virus.

During 1999 and 2000, a disease outbreak of West Nile (WN) virus occurred in humans, horses, and wild and zoological birds in the northeastern USA. In our experiments, WN virus infection of young domestic geese (Anser anser domesticus) caused depression, weight loss, torticollis, opisthotonus, and death with accompanying encephalitis and myocarditis. Based on this experimental study and a field outbreak in Israel, WN virus is a disease threat to young goslings and viremia levels are potentially sufficient to infect mosquitoes and transmit WN virus to other animal species.

Decisions at hand: a decision support system on handhelds.

One of the applications of clinical information systems is decision support. Although the advantages of utilizing such aids have never been theoretically disputed, they have been rarely used in practice. The factor that probably often limits the utility of clinical decision support systems is the need for computing power at the very site of decision making--at the place where the patient is interviewed, in discussion rooms, etc. The paper reports on a possible solution to this problem. A decision-support shell LogReg is presented, which runs on a handheld computer. A general schema for handheld-based decision support is also proposed, where decision models are developed on personal computers/workstations, encoded in XML and then transferred to handhelds, where the models are used within a decision support shell. A use case where LogReg has been applied to clinical outcome prediction in crush injury is presented.

Cost-Effectiveness of interferon alfa-2b added to chemotherapy for high-tumor-burden follicular non-Hodgkin's lymphoma.

UNLABELLED: Recent data from GELF (Groupe d'Etude des Lymphomes Folliculaires) have shown that the addition of interferon alfa-2b (IFN) to a doxorubicin-containing regimen (CHVP: cyclophosphamide, doxorubicin, teniposide and prednisone) prolongs both progression-free survival and overall survival in high-tumor-burden follicular non-Hodgkin's lymphoma. This gain must be weighed against the incremental toxicity and cost of IFN over CHVP alone and the objective here was, to determine the marginal cost-effectiveness of additive IFN in the specific setting of high-tumor-burden follicular non-Hodgkin's lymphoma. Meta-analysis of GELF trial results employing a Markov model was used with three health states: No Progression, Progressive Disease, and Death. Treatment response, survival and toxicity data are drawn from the GELF study. The current study is based on the final analysis of 242 patients (J Clin Oncol 1998;16:2332-2338), with a six year median follow-up for overall survival (median overall survival: not reached for CHVP + IFN vs 5.6 years for CHVP Only, p = 0.008). MEASUREMENTS: Quality of life data (utilities) are taken from studies with similar dosing of IFN, from Q-TwiST (quality adjusted time without symptoms or toxicity) analysis of the GELF data and from a panel of experts gathered to develop treatment models for high-tumor-burden follicular non-Hodgkin's lymphoma. Costs and quality-adjusted years of life saved were discounted at 3% per annum. SETTING: Costs determined for university medical centers in the United States. Results showed that, at the median cohort age of 52, IFN add 9.9 quality-adjusted months at an added cost of $13,900 (marginal cost-effectiveness of $16,900 per quality-adjusted life year, or QALY). A more complex, two-stage model approximates the actual cohort survival curves much better than a simple, one-stage model, but both models yield essentially the same marginal cost-effectiveness. Sensitivity analysis to quality of life on IFN shows marginal cost-effectiveness ranging from $15,200/QALY (no penalty for IFN) to $21,300/QALY (20% quality adjustment, greater than that reported). The model is quite insensitive to the probability of IFN toxicity. The model is moderately sensitive to the efficacy of IFN in delaying progression, particularly in the first 18 months (pProgI), but the marginal cost-effectiveness does not rise to $50,000/QALY until pProgI increases 220% from the baseline. Although the model is moderately sensitive to the cost of IFN (cIFN), marginal cost-effectiveness is below $50,000/QALY for values of cIFN below $2580/month (baseline cIFN = $850/month, corresponding to a marginal cost-effectiveness of $16,900/QALY in the baseline case). If the model is modified to reflect the 14% overall survival advantage at five years found in trials utilizing more intensive initial chemotherapy (including the GELF trial), then the marginal cost-effectiveness drops to $11,900/QALY in the baseline case. In condusion, based on data from the GELF study, low-dose interferon alfa-2b is cost-effective when added to CHVP therapy in the treatment of high-tumor-burden follicular non-Hodgkin's lymphoma. The analysis is robust: the model employs very conservative assumptions, and additive IFN remains cost-effective over wide ranges of variables in sensitivity analyses. The marginal cost-effectiveness is best expressed as being in the range of $12,000/QALY to $17,000/QALY in the baseline case. A simple Markov model can be used to describe treatment regimens with distinct periods of therapy.

Efficacy of vaccines in chickens against highly pathogenic Hong Kong H5N1 avian influenza.

In 1997, highly pathogenic (HP) H5N1 avian influenza virus (AIV) caused infections in poultry in Hong Kong and crossed into humans, resulting in a limited number of infections including 18 hospitalized cases and six associated deaths. The unique ability of this, AIV to infect both poultry and people raised a concern for the potential of humans to be biological as well as mechanical vectors of this AIV to poultry. The current study was undertaken to determine if existing vaccines and their technologies could be used during an outbreak to protect poultry. Commercial and experimental inactivated whole H5 AIV and baculovirus-expressed AIV H5 hemagglurinin protein vaccines provided protection from clinical signs and death in chickens after lethal challenge by human-origin HP H5N1 Hong Kong strains 156/97 and 483/97. The commercial and experimental inactivated vaccines had mean protective doses ranging from 0.25 to 0.89, which represents the milligrams of viral protein in the vaccines that provided protection from death in half of the birds. Furthermore, the vaccines reduced the ability of the challenge AIV to replicate in chickens and decreased the recovery of challenge AIV from the enteric and respiratory tracts, but the use of a vaccine will nor totally prevent AI virus replication and shedding. Existing vaccines will protect poultry from mortality and reduce virus replication from the new HP AIV strain that can infect both poultry and humans.

Cytarabine added to interferon improves the cost-effectiveness of initial therapy for patients with early chronic phase chronic myelogenous leukemia.

The French Chronic Myeloid Leukemia Study Group prospective randomized study results indicate that the addition of cytarabine to alpha interferon (IFN-alpha) increases the rate of major cytogenetic response and prolongs survival in patients with early chronic phase chronic myelogenous leukemia (CML). The French group study design permitted a single crossover to include or discontinue cytarabine or interferon. Endpoints were overall survival, complete hematologic remission (CHR) at six months, and major cytogenetic response at 12 months. We modified a published Markov model that compared IFN-alpha alone to IFN-alpha plus cytarabine and included the possibility of crossover as in the French study. The model permits allogeneic and autologous stem cell transplantation (SCT), and follows cytogenetic response and acceleration of CML through death. Treatment response, toxicity, and survival are drawn from the French Chronic Myeloid Leukemia Study Group population of 810 patients on an intention-to-treat model. Survivals are extended to 62 months based on currently available follow-up. Costs from a United States oncology specialty institution, and state utilities from previous research and a quality-adjusted Time Without Symptoms or Toxicity analysis of the subject study were discounted at 3% per annum. At the median cohort age of 50, cytarabine offers 21 months of added median survival to IFN-alpha, which itself is superior to conventional chemotherapy by 21 months. Cost-effectiveness estimates for cytarabine added to IFN-alpha range from $7,000 per quality-adjusted life year (QALY) to $35,000 per QALY, under all plausible assumptions superior to IFN-alpha alone. The model is sensitive to the quality of life on therapy, as well as to remission rate with additive cytarabine, although the cost-effectiveness calculations are robust over the entire range of clinical assumptions. Based on data from the French study, cytarabine added to IFN-alpha substantially improves the cost-effectiveness of initial therapy for early chronic phase CML.

Cardiac surgical patients exposed to heparin-bonded circuits develop less postoperative cerebral dysfunction than patients exposed to non-heparin-bonded circuits.

A prospective randomized trial was used to study the incidence of cerebral dysfunction in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded vs non-heparin-bonded circuits. Although the etiology of postoperative cerebral dysfunction is controversial, activation of the systemic inflammatory response may play a role. After institutional approval and informed written consent, 39 elective coronary artery bypass (CABG) patients were studied. A battery of neuropsychometric tests (NPMTs) was performed preoperatively, and 5 days and 6 weeks postoperatively. Significant change in NPMT performance was defined as a 25% or greater decrease in postoperative performance, compared to baseline. The number of abnormal tests per patient was calculated. Analysis using the Mann-Whitney rank test was performed for the first follow-up. Patients randomized to heparin-bonded circuits had fewer abnormal NPMTs (>1 abnormal test) on postoperative day 5 (58 vs 70%, n=19 and 20) than patients randomized to non-heparin-bonded circuits. Patients exposed to heparin-bonded circuits had fewer abnormal tests (>1 abnormal test) at 6 weeks (36 vs 63%, n=14 and 16). Results suggested that the attenuation of systemic inflammation by heparin-bonded CPB circuits may lower the incidence of cerebral injury in cardiac surgical patients.

Predicting patient's long-term clinical status after hip arthroplasty using hierarchical decision modelling and data mining.

Construction of a prognostic model is presented for the long-term outcome after femoral neck fracture treatment with implantation of hip endoprosthesis. While the model is induced from the follow-up data, we show that the use of additional expert knowledge is absolutely crucial to obtain good predictive accuracy. A schema is proposed where domain knowledge is encoded as a hierarchical decision model of which only a part is induced from the data while the rest is specified by the expert. Although applied to hip endoprosthesis domain, the proposed schema is general and can be used for the construction of other prognostic models where both follow-up data and human expertise is available.

Reanalysis of unruptured intracranial aneurysm management: effect of a new international study on the threshold probabilities.

OBJECTIVE: This report updates previous clinical decision analysis for patients with unruptured intracranial aneurysm (UN-AN) based on newly published data and discusses the role of reanalysis in individual decision making. METHODS: The authors employed probabilities for the natural history of UN-AN and results of preventive surgery based on the report by the International Study of Unruptured Intracranial Aneurysms. Probabilistic sensitivity analysis with Monte Carlo simulation and traditional n-way sensitivity analyses were used to assess the uncertainty of clinical decisions. RESULTS: The baseline decision in favor of preventive surgery is reversed by new data from the international study. Probabilistic sensitivity analyses revealed several populations showing heterogeneity in terms of strategy selection. One- and two-way sensitivity analyses detected two important factors for decision making: annual rupture rate and utility for knowingly living with UN-AN. CONCLUSIONS: Annual UN-AN rupture rate and the utility for knowingly living with UN-AN are key factors when deciding on a therapeutic strategy. Also, updating published decision analyses can improve clinical decision making by integrating clinical judgment and newly available clinical data.

Laboratory testing under managed care dominance in the USA.

The uncontrolled escalation of total health care expenditure despite the government's endeavours during the past decades in the USA had led to the rapid infiltration of managed care organisations (MCOs). Traditional hospital based laboratories have been placed in a crucial situation with the advent of the managed care era. A massive reduction of in house testing urged them to develop strategies against financial difficulty. Consolidation and networking, participation in the outreach testing market, and emphasis on point of care/satellite laboratory testing in non-traditional, ambulatory settings are major strategies for the survival of hospital laboratories. Several physicians' office laboratories (POLS) have closed their doors in response both to regulatory restrictions imposed by the Clinical Laboratory Improvement Amendments of 1988 and to managed care infiltration. It seems likely that POLs and hospital laboratories will continue to reduce test volumes, whereas commercial reference laboratories will thrive through contracting with MCOs. In the current climate of managed care dominance in the USA, clinical laboratories are changing their basic operation focus and mission in response to the aggressively changing landscape.

Decision analysis of prophylactic treatment for patients with high-risk esophageal varices.

BACKGROUND: Clinical decision analyses were conducted to quantify the uncertainty and to identify important factors in selection of prophylactic therapy for patients with esophageal varices. METHODS: A Markov model compared variceal ligation, beta-blockers, and "watchful waiting" strategies in terms of bleeding-free life years. Transition probabilities were obtained from meta-analyses of published data. A hypothetical 50-year-old white man with high-risk esophageal varices and cirrhosis served as the prototypical baseline case. Traditional n-way sensitivity analyses were applied to clarify the influence of each factor, and Monte Carlo probabilistic sensitivity analyses were used to investigate clinical uncertainty. RESULTS: Probabilistic sensitivity analyses demonstrated that 77.0% of hypothetical cases had more bleeding-free life years after variceal ligation, whereas 23% had more when treated with beta-blockers. On the basis of one-way sensitivity analyses, only 2 factors (variceal bleeding rates after ligation and treatment with beta-blockers) influenced the strategy choice. CONCLUSIONS: Variceal ligation is an effective prophylactic therapy in many cases, but nearly one quarter of patients with high-risk esophageal varices and cirrhosis may benefit more from prophylactic treatment with beta-blockers. Additional clinical studies identifying key variceal bleeding risk factors may lead to more effective clinical decision making for these patients.

A randomized trial of antithrombin concentrate for treatment of heparin resistance.

BACKGROUND: Heparin resistance is an important clinical problem traditionally treated with additional heparin or fresh frozen plasma. We undertook a randomized clinical trial to determine if treatment with antithrombin (AT) concentrate is effective for treating this condition. METHODS: Patients requiring cardiopulmonary bypass who were considered to be heparin resistant (activated clotting time < 480 seconds after > 450 IU/kg heparin) were randomized to receive either 1000 U AT or additional heparin. RESULTS: AT concentrate was effective in 42 of 44 patients (96%) for immediately obtaining a therapeutic activated clotting time. This compared favorably to 28 of 41 patients (68%) treated with additional heparin (p = 0.001). All patients who failed heparin therapy were successfully treated with AT. The patients receiving AT required less time to obtain an adequate ACT but there was no difference in clinical outcomes among the groups. Study patients had deficient AT activity at baseline (56%+/-25%), which improved in those given AT concentrate (75%+/-31% versus 50%+/-23%, p < 0.0005). CONCLUSIONS: Heparin resistance is frequently associated with AT deficiency. Treating this deficiency with AT concentrate is more effective and faster for obtaining adequate anticoagulation than using additional heparin.