Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Production of Dichloroacetonitrile from Derivatives of Isoxaflutole Herbicide during Water Treatment.

The herbicide isoxaflutole has the potential to contaminate drinking water directly, as well as upon hydrolyzing to its active form diketonitrile. Diketonitrile also may impact water quality by acting as a precursor for dichloroacetonitrile (DCAN), which is an unregulated but highly toxic disinfection byproduct (DBP). In this study, we investigated the reaction of diketonitrile with free chlorine and chloramine to form DCAN. We found that diketonitrile reacts with free chlorine within seconds but reacts with chloramine on the time scale of hours to days. In the presence of both oxidants, DCAN was generated at yields up to 100%. Diketonitrile reacted fastest with chlorine at circumneutral pH, which was consistent with base-catalyzed halogenation involving the enolate form of diketonitrile present at alkaline pH and electrophilic hypochlorous acid, which decreases in abundance above its pKa (7.5). In contrast, we found that diketonitrile reacts faster with chloramine as pH values decreased, consistent with an attack on the enolate by electrophilic protonated monochloramine that increases in abundance at acidic pH approaching its pKa (1.6). Our results indicate that increasing isoxaflutole use, particularly in light of the recent release of genetically modified isoxaflutole-tolerant crops, could result in greater occurrences of a high-yield DCAN precursor during disinfection.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Carboplatin dosing in the era of IDMS-creatinine; the Cockroft-Gault formula no longer provides a sufficiently accurate estimate of glomerular filtration rate for routine use in clinical care.

BACKGROUND: Glomerular filtration rate (GFR) measured by Chromium-51-EDTA excretion (51Cr-GFR) is considered the gold standard of renal function assessment, but serum creatinine in the Cockcroft-Gault (CG) formula is routinely used to estimate GFR for carboplatin dosing. Serum creatinine measured by isotope-dilution-mass-spectrometry (IDMS) can generate spuriously high GFR estimates when used in the CG formula. We hypothesized that GFR calculated using IDMS-creatinine in the CG formula (CG-GFR) exposes patients to inaccurate carboplatin dosing. METHODS: This is a multicenter retrospective study of patients who had a 51Cr-GFR assessment for malignant or non-malignant indications, with a matched CG-GFR. Carboplatin dose based on 51Cr-GFR at AUC5 was used as the reference. RESULTS: 550 patients were analyzed, median age 62 (19-90), 64% female. Indication for GFR evaluation: malignancy (85%), assessment for live kidney donation (12%), other (3%). Median ratio of CG-GFR: 51Cr-GFR 1.04 (0.43-3.38); <0.8 in 72 patients (13%), >1.2 in 180 patients (33%). Despite capping of CG-GFR at 125 mL/min, dosing according to AUC6 would have resulted in 18% of patients being underdosed and 23% overdosed by >100 mg compared to 51Cr-GFR. Subgroup analysis identified BMI (>35, MPE 39%), gender (female MPE 15%), GFR indication (malignancy MPE 11%) as risk factors for overestimate of CG-GFR, and BMI < 20 for underestimate (MPE -3.5%). CONCLUSIONS: The convention of considering AUC5 carboplatin based on 51Cr-GFR, and AUC6 carboplatin based on CG-GFR as equivalent is invalid and should be abandoned. When 51Cr-GFR is unavailable, capping CG-GFR at 125 mL/min is recommended.

An evaluation of a citizen science data collection program for recording wildlife observations along a highway.

Citizen science programs that record wildlife observations on and along roads can help reduce the underreporting of wildlife-vehicle collisions and identify and prioritize road sections where mitigation measures may be required. It is important to evaluate potential biases in opportunistic citizen science data. We investigated whether the opportunistic observations of live animals by volunteers along a 46-km section of Highway 3 in the Crowsnest Pass area ("Road Watch in the Pass" data collection program) in Alberta, Canada, had a similar spatial pattern as systematically collected data by the researchers along the same road section. A permutation modeling process that compared the number of observations between the two datasets for each 1-km segment, a randomization method that tested for and compared hotspot observation locations, and a bivariate Ripley's L1.2-function analysis along a continuum of spatial scales all showed spatial agreement between the two datasets. There was spatial agreement at a scale between 1 and 4 km, and three clear hotspots of wildlife observation activity were identified for both processes. This suggests that the data collected by the volunteers are reliable and robust enough to be used to help identify road sections that may require mitigation measures. In addition, volunteers proved to be able to collect a sufficient number of observations relatively quickly. Within one year, 24 volunteers collected 640 wildlife observations, and we found that using only 150 or more of these observations always resulted in spatial similarity with the systematic observations collected by the researchers. We conclude with recommendations for other citizen science data collection programs and for further research.

Public Health Impact of the Adjuvanted RSVPreF3 Vaccine for Respiratory Syncytial Virus Prevention Among Older Adults in the United States.

INTRODUCTION: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. METHODS: This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60 years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). RESULTS: In the base-case analysis, approximately 56.7 million adults aged ≥ 60 years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3 years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. CONCLUSIONS: These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60 years.

The threat of groundwater pollution for petrifying springs; defining nutrient threshold values for an endangered bryophyte dominated habitat.

Eutrophication by human activities is increasingly affecting ecosystem functioning and plant community composition. So far, studies mainly focus on the effects of atmospheric nitrogen deposition, surface water eutrophication or soil nutrient accumulation. Groundwater pollution of spring habitats, however, has received much less attention, although numerous papers report groundwater nutrient enrichment worldwide. This study presents a survey on groundwater pollution (with emphasis on nitrate and phosphate) and bryophyte composition in 51 ambient petrifying springs in 5 NW European countries, which were compared to published data from 173 other sites in 11 European countries. The reviewed dataset covers a broad range of unpolluted to heavily polluted springs with nitrate concentrations between 0.7 and 3227 µmol l-1. Most petrifying springs in the rural lowlands of NW Europe were found to have elevated concentrations of nitrate and phosphate with the most polluted springs occurring in The Netherlands. The cover of individual characteristic bryophyte species significantly correlates with groundwater nutrient concentrations indicating that nutrient pollution of spring waters affects bryophyte composition. Palustriella commutata, Eucladium verticillatum and Brachythecium rivulare prefer unpolluted petrifying springs whereas Cratoneuron filicinum and Pellia endiviifolia show a much broader tolerance to groundwater pollution. In order to sustain at least the basic conditions for the typical bryophyte composition of petrifying springs habitats, threshold values of 288 µmol (18 mg l-1) NO3- l-1 and 0.42 µmol (0.04 mg l-1) ortho-PO43- l-1 were defined. Data analysis of the spring water composition indicates that the main source for nutrient and nutrient induced base cation enrichment are nitrate losses from intensively used agricultural fields. The anthropogenically induced but regionally different chemical processes in subsoil and aquifers can result in different levels of nutrient pollution in springs. Further regulations for nitrate and phosphate application are required to conserve and restore groundwater fed ecosystems in Europe.

Geographic proximity to immunization providers and vaccine series completion among children ages 0-24 months.

OBJECTIVES: In the U.S., vaccination coverage is lower in rural versus urban areas. Spatial accessibility to immunization services has been a suspected risk factor for undervaccination in rural children. Our objective was to identify whether geographic factors, including driving distance to immunization providers, were associated with completion of recommended childhood vaccinations. METHODS: We analyzed records from Montana's immunization information system for children born 2015-2017. Using geolocated address data, we calculated distance in road miles from children's residences to the nearest immunization provider. A multivariable log-linked binomial mixed model was used to identify factors associated with completion of the combined 7-vaccine series by age 24 months. RESULTS: Among 26,085 children, 16,503 (63.3%) completed the combined 7-vaccine series by age 24 months. Distance to the nearest immunization provider ranged from 0 to 81.0 miles (median = 1.7; IQR = 3.2), with the majority (92.1%) of children living within 10 miles of a provider. Long distances (>10 miles) to providers had modest associations with not completing the combined 7-vaccine series (adjusted prevalence ratio [aPR]: 0.97, 95% confidence interval [CI]: 0.96-0.99). After adjustment for other factors, children living in rural areas (measured by rural-urban commuting area) were significantly less likely to have completed the combined 7-vaccine series than children in metropolitan areas (aPR: 0.88, 95% CI: 0.85-0.92). CONCLUSIONS: Long travel distances do not appear to be a major barrier to childhood vaccination in Montana. Other challenges, including limited resources for clinic-based strategies to promote timely vaccination and parental vaccine hesitancy, may have greater influence on rural childhood vaccination.

Cost and health impact analysis of herpes zoster vaccination in Norway.

BACKGROUND: A decision analytic model was developed to estimate the cost-effectiveness of a national vaccination program against herpes zoster in Norway. METHODS: The model analyzed six vaccination scenarios that included the live-attenuated zoster vaccine under different target ages of vaccination (60, 65, and 70 years) compared with no vaccination. A catch-up program implemented in the first year of the vaccination was included in three of the scenarios. The model followed the population of Norway over a 40-year time horizon to estimate costs and outcomes associated with vaccination. Immunization costs, costs related to herpes zoster (both healthcare sector and non-healthcasre sector), the quality of life gains due to avoided cases of herpes zoster, and quality-of-life losses due to vaccine-related adverse events were estimated. RESULTS AND CONCLUSIONS: A national vaccination program would result in reduction of the number of herpes zoster cases and decreased burden of illness. Vaccinating adults at 65 years of age with catch-up up to 70 years in the first year of the program was the most cost-effective strategy with the incremental cost per quality-adjusted life-year gained at NOK (Norwegian Krone) 245,459 from the societal perspective and NOK 248,637 from the health care system perspective.

Interrogating intervention delivery and participants' emotional states to improve engagement and implementation: A realist informed multiple case study evaluation of Engager.

BACKGROUND: 'Engager' is an innovative 'through-the-gate' complex care intervention for male prison-leavers with common mental health problems. In parallel to the randomised-controlled trial of Engager (Trial registration number: ISRCTN11707331), a set of process evaluation analyses were undertaken. This paper reports on the depth multiple case study analysis part of the process evaluation, exploring how a sub-sample of prison-leavers engaged and responded to the intervention offer of one-to-one support during their re-integration into the community. METHODS: To understand intervention delivery and what response it elicited in individuals, we used a realist-informed qualitative multiple 'case' studies approach. We scrutinised how intervention component delivery lead to outcomes by examining underlying causal pathways or 'mechanisms' that promoted or hindered progress towards personal outcomes. 'Cases' (n = 24) were prison-leavers from the intervention arm of the trial. We collected practitioner activity logs and conducted semi-structured interviews with prison-leavers and Engager/other service practitioners. We mapped data for each case against the intervention logic model and then used Bhaskar's (2016) 'DREIC' analytic process to categorise cases according to extent of intervention delivery, outcomes evidenced, and contributing factors behind engagement or disengagement and progress achieved. RESULTS: There were variations in the dose and session focus of the intervention delivery, and how different participants responded. Participants sustaining long-term engagement and sustained change reached a state of 'crises but coping'. We found evidence that several components of the intervention were key to achieving this: trusting relationships, therapeutic work delivered well and over time; and an in-depth shared understanding of needs, concerns, and goals between the practitioner and participants. Those who disengaged were in one of the following states: 'Crises and chaos', 'Resigned acceptance', 'Honeymoon' or 'Wilful withdrawal'. CONCLUSIONS: We demonstrate that the 'implementability' of an intervention can be explained by examining the delivery of core intervention components in relation to the responses elicited in the participants. Core delivery mechanisms often had to be 'triggered' numerous times to produce sustained change. The improvements achieved, sustained, and valued by participants were not always reflected in the quantitative measures recorded in the RCT. The compatibility between the practitioner, participant and setting were continually at risk of being undermined by implementation failure as well as changing external circumstances and participants' own weaknesses. TRIAL REGISTRATION NUMBER: ISRCTN11707331, Wales Research Ethics Committee, Registered 02-04-2016-Retrospectively registered https://doi.org/10.1186/ISRCTN11707331.

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States.

OBJECTIVE: The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. STUDY DESIGN: A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. RESULTS: The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. CONCLUSION: Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

Effects of greenery enhancements for the resilience to heat waves: A comparison of analysis performed through mesoscale (WRF) and microscale (Envi-met) modeling.

Given the large transformation and fast-growing population that the Greater Toronto Area (GTA) is facing, and the increasing impact of climate change in urbanized areas, it is crucial to investigate strategies that could mitigate the effects of heat waves. In this paper, the effects of greenery enhancements are investigated using mesoscale and microscale simulations performed by the Weather Research and Forecasting model and the ENVI-met model, respectively. In particular, two vulnerable areas located in the GTA are investigated. Comparing the results of simulations with measurements show the differences in how mesoscale and microscale models predict the meteorological processes happening within the urban canopy and the local climate. Then, two mitigation scenarios, a moderate green scenario (MGS) and an intensive green scenario (IGS) are assessed considering different increases in the vegetation area. The results of the mesoscale simulations show that by increasing the greenery canopy, the maximum daily air temperature decreases by 1.6 to 2.3 °C, while the relative humidity increases by 10% to 12%. The microscale simulations show that increasing the tree canopy would cool the air temperature by 0.5 °C to 1.4 °C locally. Overall, depending on wind conditions and the arrangement of buildings and existing green areas, the cooling effect is shown to have an impact on up to 250 m downwind from the new green area locations. Finally, this study demonstrates that both mesoscale (WRF) and microscale (ENVI-met) modeling confirm similar results in how greenery enhancements may improve the human thermal comfort in the continental climate of the GTA.

The delayed effect of wildfire season particulate matter on subsequent influenza season in a mountain west region of the USA.

Particularly in rural settings, there has been little research regarding the health impacts of fine particulate matter (PM2.5) during the wildfire season smoke exposure period on respiratory diseases, such as influenza, and their associated outbreaks months later. We examined the delayed effects of PM2.5 concentrations for the short-lag (1-4 weeks prior) and the long-lag (during the prior wildfire season months) on the following winter influenza season in Montana, a mountainous state in the western United States. We created gridded maps of surface PM2.5 for the state of Montana from 2009 to 2018 using spatial regression models fit with station observations and Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol optical thickness data. We used a seasonal quasi-Poisson model with generalized estimating equations to estimate weekly, county-specific, influenza counts for Montana, associated with delayed PM2.5 concentration periods (short-lag and long-lag effects), adjusted for temperature and seasonal trend. We did not detect an acute, short-lag PM2.5 effect nor short-lag temperature effect on influenza in Montana. Higher daily average PM2.5 concentrations during the wildfire season was positively associated with increased influenza in the following winter influenza season (expected 16% or 22% increase in influenza rate per 1 µg/m3 increase in average daily summer PM2.5 based on two analyses, p = 0.04 or 0.008). This is one of the first observations of a relationship between PM2.5 during wildfire season and influenza months later.

Budget impact analysis of multiple varicella vaccination strategies: a Mexico perspective.

A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.

Lagrangian-averaged model for magnetohydrodynamic turbulence and the absence of bottlenecks.

We demonstrate that, for the case of quasiequipartition between the velocity and the magnetic field, the Lagrangian-averaged magnetohydrodynamics (LAMHD) alpha model reproduces well both the large-scale and the small-scale properties of turbulent flows; in particular, it displays no increased (superfilter) bottleneck effect with its ensuing enhanced energy spectrum at the onset of the subfilter scales. This is in contrast to the case of the neutral fluid in which the Lagrangian-averaged Navier-Stokes alpha model is somewhat limited in its applications because of the formation of spatial regions with no internal degrees of freedom and subsequent contamination of superfilter-scale spectral properties. We argue that, as the Lorentz force breaks the conservation of circulation and enables spectrally nonlocal energy transfer (associated with Alfvén waves), it is responsible for the absence of a viscous bottleneck in magnetohydrodynamics (MHD), as compared to the fluid case. As LAMHD preserves Alfvén waves and the circulation properties of MHD, there is also no (superfilter) bottleneck found in LAMHD, making this method capable of large reductions in required numerical degrees of freedom; specifically, we find a reduction factor of approximately 200 when compared to a direct numerical simulation on a large grid of 1536;{3} points at the same Reynolds number.

Cost effectiveness of glatiramer acetate and natalizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Disease-modifying drugs are a significant expenditure for treating multiple sclerosis. Natalizumab (NZ) has been shown to be effective in reducing relapses and disease progression. However, assessment of the cost effectiveness of NZ compared with other disease-modifying drugs in the presence of long-term data has been limited. OBJECTIVE: To assess the lifetime cost effectiveness from the US healthcare and societal perspectives of glatiramer acetate (GA) and NZ (both given with symptom management) relative to symptom management alone in patients with relapsing-remitting multiple sclerosis (RRMS) using evidence from long-term published studies. METHODS: A Markov model was developed with patients transitioning through health states based on Kurtzke's expanded disability status scale (EDSS). Patients were >/=18 years of age with RRMS, EDSS <6.0 and receiving treatment. Treatment effects were obtained from clinical trials for years 1 and 2 of therapy and long-term clinical assessments thereafter. Transitions were adjusted for discontinuation and persistent NZ antibodies. Patients incurred drug, other medical and lost worker productivity costs. Patient quality of life was considered in the form of utilities, which were taken from assessments of patients with MS. Costs were valued in 2007 $US, and costs and outcomes were discounted at 3% per annum. Various parameters and assumptions were tested in one-way sensitivity analyses, and scenario-based analyses were also performed. RESULTS: Remaining lifetime, direct medical costs for patients receiving GA or NZ versus symptom management were $US408 000, $US422 208 and $US341 436, respectively. Patients receiving GA or NZ benefited from increased years in EDSS 0.0-5.5 (1.18 and 1.09, respectively), years relapse-free (1.30 and 1.18) and QALYs (0.1341 and 0.1332). The incremental cost per QALY for GA or NZ compared with symptom management was $US496 222 and $US606 228, respectively, excluding lost worker productivity costs. GA was associated with a cost saving compared with NZ. The incremental cost per QALY results were sensitive to changes in time horizon, disease progression and drug costs. Improved QALYs for NZ were sensitive to changes in the clinical effect of NZ on disease progression and discontinuation over time. CONCLUSIONS: GA or NZ in RRMS patients is associated with increased benefits compared with symptom management, albeit at higher costs. Although year 1 and 2 disease progression and relapse rates were better for NZ than GA, long-term evidence may show GA to have similar, if not improved, clinical benefit.

Long-Term Outcome of Long Stay ICU and HDU Patients in a New Zealand Hospital.

OBJECTIVE: The objective of the study is to determine factors that influence the outcome of long stay patients in a general intensive care unit (ICU) and/or high-dependency unit (HDU) in a New Zealand teaching hospital. SETTING: 10-bed general ICU and 4-bed surgical HDU in a 400-bed hospital. STUDY TYPE: Population based retrospective cohort study. METHODS: All patients with prolonged stay in a high resource area (>7 days in the ICU or >14 days in either the ICU or HDU) between 2000 and 2003 were reviewed. Demographic data, co-morbidities, diagnoses, clinical events, hospital and 1-year mortality data were obtained using available databases and patient records. Multiple logistic regression analysis was performed to identify which variables are associated with death among patients with a prolonged stay in a high-resource unit (ICU/HDU). RESULTS: 207 patients were included in the study. Twenty eight percent died before hospital discharge and 40% died within one year of their admission. Univariate analysis showed that increasing age, APACHE II score, admission post cardiac arrest, inpatient cardiac arrest, development of sepsis and requirement for renal support therapy were all risk factors for increased mortality. However, when adjusted for age, gender and APACHE II score the only risk factor strongly associated with death was having a cardiac arrest in the ICU. CONCLUSIONS: Prolonged ICU and/or HDU stay is associated with a high mortality rate particularly in patients with advancing age and increasing severity of illness. In this study, only cardiac arrest after a prolonged stay in the ICU and/or HDU is a strong predictor of death independent of the age and the APACHE II score.

Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

BACKGROUND: Afatinib is 1 of 3 tyrosine kinase inhibitors approved in the United States for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations. In clinical trials, afatinib has demonstrated improvement in progression-free survival versus standard chemotherapy and gefitinib. OBJECTIVE: To analyze the impact of increases in afatinib treatment share on the cost and health outcomes in a commercial health plan in the United States. METHODS: A decision model was developed to evaluate the budget impact of increases in afatinib share for the first-line treatment of patients with metastatic NSCLC with EGFR del19 or L858R substitution mutations over a 5-year time horizon. The model compared the total annual costs for a health plan with 1 million covered lives in a scenario in which afatinib share increased 5 percentage points annually to one in which all treatment shares remained constant over time. The number of patients eligible for treatment was estimated using published incidence data. Therapies included in the model were afatinib, erlotinib, gefitinib, and the chemotherapy doublet, pemetrexed in combination with cisplatin. The mean time spent by patients in progression-free and progressive disease states was based on survival data from clinical trials and a network meta-analysis. Therapy-related costs included monthly drug acquisition and administration costs and costs of managing adverse reactions. Disease management costs were also assessed in the model. Scenario analyses were performed to assess alternative scenarios of afatinib treatment share. Additionally, a one-way sensitivity analysis was performed to test the robustness of the model, given parameter uncertainty. RESULTS: Using the base-case parameter assumptions and a 5-percentage-point annual increase in afatinib treatment share, we estimated the total budget increases in years 1 through 5 to be $1,606, $65,542, $140,564, $209,272, and $303,368, respectively. These budget increases translated to per-member-per-month increases ranging from $0.00 to $0.03 in years 1 to 5. The increase in afatinib use resulted in the proportion of the treated population (134 patients treated over 5 years) remaining in progression-free disease increasing from 23.7% to 26.2% at the end of year 5, versus if afatinib treatment share had stayed constant. CONCLUSIONS: Increasing the treatment share of afatinib in a health plan for the first-line treatment of NSCLC with EGFR del19 or L858R mutations was estimated to increase the proportion of treated patients remaining in progression-free disease, while having small budget impact to the health plan. DISCLOSURES: Boehringer Ingelheim Pharmaceuticals funded this study research and was involved in all stages of study conduct, including the analysis of data, and also undertook all costs associated with the development and publication of this manuscript. Graham and Earnshaw are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from Boehringer Ingelheim Pharmaceuticals. Lim and Burslem are employees of Boehringer Ingelheim Pharmaceuticals, which developed and produces afatinib, along with other pharmaceutical products.