Rare

Potassium-40 is a widespread, naturally occurring isotope whose radioactivity impacts subatomic rare-event searches, nuclear structure theory, and estimated geological ages. A predicted electron-capture decay directly to the ground state of argon-40 has never been observed. The KDK (potassium decay) collaboration reports strong evidence of this rare decay mode. A blinded analysis reveals a nonzero ratio of intensities of ground-state electron-captures (I_{EC^{0}}) over excited-state ones (I_{EC^{*}}) of I_{EC^{0}}/I_{EC^{*}}=0.0095±[over stat]0.0022±[over sys]0.0010 (68% C.L.), with the null hypothesis rejected at 4σ. In terms of branching ratio, this signal yields I_{EC^{0}}=0.098%±[over stat]0.023%±[over sys]0.010%, roughly half of the commonly used prediction, with consequences for various fields [27L. Hariasz et al., companion paper, Phys. Rev. C 108, 014327 (2023)PRVCAN2469-998510.1103/PhysRevC.108.014327].

ß-Delayed One and Two Neutron Emission Probabilities Southeast of

The ß-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. ß-delayed two-neutron emission (ß2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak ß2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on ß-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data.

Coexistence of Reflection Asymmetric and Symmetric Shapes in

Level structures in the neutron-rich ^{144}Ba nucleus have been reinvestigated by measuring prompt γ rays in the spontaneous fission of ^{252}Cf. The previous s=+1 octupole band structure with reflection asymmetric shape has been expanded, and a side quadrupole band structure based on a 3^{+} state with reflection symmetric shape is identified. Thus, the results show the coexistence of reflection asymmetric and symmetric shapes in ^{144}Ba. This is a first identification of such a shape coexistence structure in a nuclear structure. The other structural characteristics are discussed.

Study of Quasielastic Barrier Distributions as a Step towards the Synthesis of Superheavy Elements with Hot Fusion Reactions.

The excitation functions for quasielastic scattering of ^{22}Ne+^{248}Cm, ^{26}Mg+^{248}Cm, and ^{48}Ca+^{238}U are measured using a gas-filled recoil ion separator. The quasielastic barrier distributions are extracted for these systems and are compared with coupled-channel calculations. The results indicate that the barrier distribution is affected dominantly by deformation of the actinide target nuclei, but also by vibrational or rotational excitations of the projectile nuclei, as well as neutron transfer processes before capture. From a comparison between the experimental barrier distributions and the evaporation residue cross sections for Sg (Z=106), Hs (108), Cn (112), and Lv (116), it is suggested that the hot fusion reactions take advantage of a compact collision, where the projectile approaches along the short axis of a prolately deformed nucleus. A new method is proposed to estimate the optimum incident energy to synthesize unknown superheavy nuclei using the barrier distribution.

Trauma memory characteristics and the development of acute stress disorder and post-traumatic stress disorder in youth.

BACKGROUND & OBJECTIVES: The present study addresses gaps in knowledge regarding the association between trauma memory processes and posttraumatic stress responses in youth. Our primary goal was to explore the relative contribution of perceptions of trauma memory quality versus narrative trauma memory characteristics to explain overall adjustment. METHODS: Children (N = 67) were interviewed within four weeks (T1) of an injury leading to hospital treatment and then again eight weeks later (T2). In each interview, the child told a trauma narrative (which were later coded), and answered the Trauma Memory Quality Questionnaire (Meiser-Stedman, Smith, Yule, & Dalgleish, 2007a), a self-report measure indexing the sensory, fragmented, and disorganised characteristics of trauma memory. They then completed measures of Acute Stress Disorder (ASD) symptoms and associated psychopathology at T1 and measures of Posttraumatic Stress (PTS) symptoms and associated psychopathology at T2. RESULTS: Self-reported trauma memory characteristics predicted ASD symptoms cross-sectionally at T1 and PTS symptoms prospectively over time. At both time points, self-reported trauma memory characteristics accounted for all of the unique variance in symptoms initially explained by narrative characteristics. A reduction in self-report ratings, but not the hypothesised narrative features (e.g., disorganised or lexical elements of the narrative), significantly predicted a reduction in PTS symptoms over time. LIMITATIONS: The small sample size and the absence of a within-subjects narrative control were the main limitations of the study. CONCLUSIONS: These findings underscore the importance of self-reported trauma memory characteristics to the aetiology of PTSD.

Decays of the Three Top Contributors to the Reactor ν[over ¯]_{e} High-Energy Spectrum,

We report total absorption spectroscopy measurements of ^{92}Rb, ^{96gs}Y, and ^{142}Cs ß decays, which are the most important contributors to the high energy ν[over ¯]_{e} spectral shape in nuclear reactors. These three ß decays contribute 43% of the ν[over ¯]_{e} flux near 5.5 MeV emitted by nuclear reactors. This ν[over ¯]_{e} energy is particularly interesting due to spectral features recently observed in several experiments including the Daya Bay, Double Chooz, and RENO Collaborations. Measurements were conducted at Oak Ridge National Laboratory by means of proton-induced fission of ^{238}U with on-line mass separation of fission fragments and the Modular Total Absorption Spectrometer. We observe a ß-decay pattern that is similar to recent measurements of ^{92}Rb, with a ground-state to ground-state ß feeding of 91(3)%. We verify the ^{96gs}Y ground-state to ground-state ß feeding of 95.5(20)%. Our measurements substantially modify the ß-decay feedings of ^{142}Cs, reducing the ß feeding to ^{142}Ba states below 2 MeV by 32% when compared with the latest evaluations. Our results increase the discrepancy between the observed and the expected reactor ν[over ¯]_{e} flux between 5 and 7 MeV, the maximum excess increases from ∼10% to ∼12%.

Evidence for Gamow-Teller Decay of

The ß-delayed neutron emission of ^{83,84}Ga isotopes was studied using the neutron time-of-flight technique. The measured neutron energy spectra showed emission from states at excitation energies high above the neutron separation energy and previously not observed in the ß decay of midmass nuclei. The large decay strength deduced from the observed intense neutron emission is a signature of Gamow-Teller transformation. This observation was interpreted as evidence for allowed ß decay to ^{78}Ni core-excited states in ^{83,84}Ge favored by shell effects. We developed shell model calculations in the proton fpg_{9/2} and neutron extended fpg_{9/2}+d_{5/2} valence space using realistic interactions that were used to understand measured ß-decay lifetimes. We conclude that enhanced, concentrated ß-decay strength for neutron-unbound states may be common for very neutron-rich nuclei. This leads to intense ß-delayed high-energy neutron and strong multineutron emission probabilities that in turn affect astrophysical nucleosynthesis models.

Adolescents' interest in trying flavoured e-cigarettes.

BACKGROUND: More US adolescents use e-cigarettes than smoke cigarettes. Research suggests flavoured e-cigarettes appeal to youth, but little is known about perceptions of and reasons for attraction to specific flavours. METHODS: A national sample of adolescents (n=1125) ages 13-17 participated in a phone survey from November 2014 to June 2015. We randomly assigned adolescents to respond to survey items about 1 of 5 e-cigarette flavours (tobacco, alcohol, menthol, candy or fruit) and used regression analysis to examine the impact of flavour on interest in trying e-cigarettes and harm beliefs. RESULTS: Adolescents were more likely to report interest in trying an e-cigarette offered by a friend if it were flavoured like menthol (OR=4.00, 95% CI 1.46 to 10.97), candy (OR=4.53, 95% CI 1.67 to 12.31) or fruit (OR=6.49, 95% CI 2.48 to 17.01) compared with tobacco. Adolescents believed that fruit-flavoured e-cigarettes were less harmful to health than tobacco-flavoured e-cigarettes (p<0.05). Perceived harm mediated the relationship between some flavours and interest in trying e-cigarettes. A minority of adolescents believed that e-cigarettes did not have nicotine (14.6%) or did not know whether they had nicotine (3.6%); these beliefs did not vary by flavour. DISCUSSION: Candy-flavoured, fruit-flavoured and menthol-flavoured e-cigarettes appeal to adolescents more than tobacco-flavoured or alcohol-flavoured e-cigarettes. This appeal is only partially explained by beliefs about reduced harm. Given adolescents' interest in trying e-cigarettes with certain flavours, policymakers should consider restricting advertisements promoting flavoured products in media that reach large numbers of young people. Future research should examine other reasons for the appeal of individual flavours, such as novelty and perceived luxury.

Patients' understanding of how genotype variation affects benefits of tamoxifen therapy for breast cancer.

BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. METHODS: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.

Large ß-delayed one and two neutron emission rates in the decay of 86Ga.

Beta decay of 86Ga was studied by means of ß-neutron-γ spectroscopy. An isotopically pure ^{86}Ga beam was produced at the Holifield Radioactive Ion Beam Facility using a resonance ionization laser ion source and high-resolution electromagnetic separation. The decay of 86Ga revealed a half-life of 43(-15)(+21) ms and large ß-delayed one-neutron and two-neutron branching ratios of P1n=60(10)% and P2n=20(10)%. The ßγ decay of 86Ga populated a 527 keV transition that is interpreted as the deexcitation of the first 2+ state in the N=54 isotone 86Ge and suggests a quick onset of deformation in Ge isotopes beyond N=50.

Who gets genomic testing for breast cancer recurrence risk?

BACKGROUND/AIMS: Our study examined whether patient characteristics, beliefs and decision-making styles were associated with uptake of genomic testing for breast cancer recurrence risk. METHODS: Participants were 132 early-stage breast cancer patients eligible for the Oncotype DX genomic test. We interviewed patients in 2009-2010 and obtained information from medical charts. RESULTS: Half of the women eligible for genomic testing for breast cancer recurrence risk received it. The most common reason for not getting the test was that women's physicians did not offer it (80%). Test recipients were more likely to be unsure about receiving chemotherapy treatment compared to women who did not receive the test (p < 0.05). Women who received the test had less advanced disease pathologies, recalled a lower objective recurrence risk, perceived lower recurrence risk, and were slightly younger (all p < 0.05). Most women who described their decision-making style as active received the test (75%), whereas few women who described their style as passive received the test (12%) (p < 0.01). CONCLUSION: In the university clinic we studied, genomic testing appeared to be more common among patients who may benefit most from the information provided by results, but confirmation in larger studies is needed.

New half-lives of r-process Zn and Ga isotopes measured with electromagnetic separation.

The ß decays of neutron-rich nuclei near the doubly magic (78)Ni were studied at the Holifield Radioactive Ion Beam Facility using an electromagnetic isobar separator. The half-lives of (82)Zn (228±10 ms), (83)Zn (117±20 ms), and (85)Ga (93±7 ms) were determined for the first time. These half-lives were found to be very different from the predictions of the global model used in astrophysical simulations. A new calculation was developed using the density functional model, which properly reproduced the new experimental values. The robustness of the new model in the (78)Ni region allowed us to extrapolate data for more neutron-rich isotopes. The revised analysis of the rapid neutron capture process in low entropy environments with our new set of measured and calculated half-lives shows a significant redistribution of predicted isobaric abundances strengthening the yield of A>140 nuclei.

Association between glycosylated hemoglobin and cancer risk: a New Zealand linkage study.

BACKGROUND: The purpose of this study was to examine the relationship between glycosylated hemoglobin (HbA(1c)) level and subsequent cancer risk. MATERIAL AND METHODS: HbA(1c) measurements were made on blood samples of participants in a hepatitis B (HB) screening program (1999-2001). Cancer incidence was determined by linkage to cancer registrations and hospitalization records to the end of 2004. Participants previously diagnosed with diabetes or cancer were excluded. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Among the 46 575 participants (70% Maori, 12% Pacific, 5% Asian and 12% Other), 634 cancer cases were observed. For all cancers combined, a significant increased risk was found in persons with moderately elevated HbA(1c) levels (6%-6.9%) (HR 1.40, 95% CI: 1.11-1.76), with a smaller increased risk in persons with highly elevated levels (> or =7%) (HR 1.09, 95% CI: 0.80-1.48) as compared with persons having low HbA(1c) levels (<6%). The HRs for respiratory cancers were 2.27 (95% CI: 1.34-3.86) for the moderate HbA(1c) category and 1.58 (95% CI: 0.77-3.26) for the upper HbA(1c) category. For endometrial cancers, the HRs were 4.05 (95% CI: 1.10-14.88) and 5.07 (95% CI: 1.20-21.31), respectively. For other cancer sites, no significantly increased risks were found. CONCLUSIONS: These findings are consistent with other evidence that abnormal glucose metabolism may be associated with an increased risk of some cancers.

A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.

OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of selective oestrogen receptor modulators, bisphosphonates and parathyroid hormone (subject to licensing) for the prevention and treatment of osteoporosis and the prevention of osteoporotic fractures in postmenopausal women. DATA SOURCES: Electronic databases. REVIEW METHODS: Studies that met the review's entry criteria were eligible for inclusion in the meta-analyses provided that they reported fracture incidence in terms of the number of patients suffering fractures. Meta-analysis was carried out using the random-effects model. A model was constructed to estimate the cost-effectiveness of osteoporosis interventions. The model calculated the number of fractures that occurred and provided the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs). In addition, the conditions of breast cancer and coronary heart disease (CHD) were modelled, as some interventions have been shown to affect the risk of these conditions. RESULTS: Ninety randomised controlled trials (RCTs) met the inclusion criteria. They related to the five interventions (alendronate, etidronate, risedronate, raloxifene and teriparatide) and to five comparators (calcium, calcium plus vitamin D, calcitriol, hormone replacement therapy and exercise), as well as placebo or no treatment. All five interventions have been shown to reduce the risk of vertebral fracture in women with severe osteoporosis with adequate calcium intakes. However, none of these drugs has been demonstrated, by direct comparison, to be significantly more effective than either each other or the other active interventions reviewed in this report. The intervention costs of treating all osteoporotic women, for a period of 5 years, were in the region of pound 900-1500 million for alendronate, etidronate, risedronate and raloxifene. The cost per QALY ratios fell dramatically with age. Assuming the risks of a woman with severe osteoporosis at the threshold of osteoporosis, no treatment had a cost per QALY below pound 35,000 at 50 years of age. At 60 years of age, the cost per QALY of raloxifene was pound 26,000 assuming no impact on hip fractures, and pound 31,000 assuming an adverse effect. However, these results are driven by the effect on breast cancer and the assumptions made regarding this disease state. No other intervention had a cost per QALY below pound 35,000. When analyses were conducted assuming that the fracture risk is doubled at each site, alendronate and risedronate had cost per QALY ratios below pound 30,000 at all ages. For women at the threshold of osteoporosis, without a prior fracture and aged 70 years, the cost per QALY of the three bisphosphonates ranged from pound 34,000 to pound 41,000. Raloxifene had a cost per QALY of pound 23,000, assuming no effect on hip fracture, given assumptions regarding breast cancer. At 80 years of age, the cost per QALY of alendronate and risedronate was below pound 20,000. This was true for etidronate when incorporating observational data, but the value rose to pound 69,000 when only RCT data were used. No other intervention had a cost per QALY below pound 35,000. It was assumed that doubling the risk of fracture for women without a prior fracture would give results similar to patients at the threshold of osteoporosis with a prior fracture. CONCLUSIONS: Of the five interventions, only raloxifene appeared to reduce the risk of vertebral fracture in postmenopausal women unselected for low bone mineral density (BMD). However, as the full data have not been made public, there is some uncertainty regarding this result. None of the five interventions has been shown to reduce the risk of non-vertebral fracture in women unselected for low BMD. All of the proposed interventions provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the age of the patient. The estimated costs varied widely for the interventions. These net costs were markedly different by age, with some interventions becoming cost-saving at higher age ranges in patients with a prior fracture. Areas for future research include: the evidence base for the efficacy of fracture prevention in the very elderly, reanalysis of raloxifene using a dedicated breast cancer and CHD model, and more trials considering the cost-effectiveness of teriparatide.

Rituximab (MabThera) for aggressive non-Hodgkin's lymphoma: systematic review and economic evaluation.

OBJECTIVES: To determine the clinical and cost-effectiveness of adding rituximab to the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy regime for adult patients with diffuse large B-cell lymphoma (DLBCL). DATA SOURCES: Electronic bibliographic database. REVIEW METHODS: Comparative studies were selected for review if they addressed the clinical or cost-effectiveness of adding rituximab to CHOP in people aged at least 18 years with DLBCL. The internal validity of the study was assessed through the use of the validated Jadad scoring system. Data were abstracted into standardised data extraction forms. Costs were estimated through resource use data taken from the published trial and the unpublished sponsor submission. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to evaluate the cost-effectiveness of R-CHOP compared with CHOP alone for patients with DLBCL using data sources and methodology similar to the manufacturer's submission. RESULTS: In the systematic review of effectiveness, one randomised controlled trial was identified. The study was, in most respects, methodologically rigorous and well conducted and the statistical evidence favoured the addition of rituximab to CHOP. The total cost of rituximab with CHOP (R-CHOP) and CHOP alone estimated from the model developed by ScHARR was 14,456 pounds and 5773 pounds, respectively, for patients aged 60 years and over, and 15,181 pounds and 7311 pounds for patients aged less than 60 years over a 15-year time horizon. The ScHARR model estimated that the addition of rituximab to CHOP generated an additional 0.82 QALY at an extra cost of 8683 pounds compared with CHOP alone therapy over a 15-year time horizon, a cost/quality-adjusted life-year (QALY) ratio of 10,596 pounds for patients aged 60 years or more. For patients aged under 60 years, 1.05 QALY were generated at an additional cost of 7870 pounds, a cost/QALY ratio of 7533 pounds. Assuming that the societal value of a QALY was 30,000 pounds then R-CHOP is cost-effective compared with CHOP in the treatment of DLBCL. CONCLUSIONS: In the short term, the addition of rituximab to the CHOP regimen increased the likelihood of a complete-response by 20% without a significant rise in the risk of a serious adverse event in people aged 60 years or older. Over a 2-year follow-up period, the intervention reduced the risk of death, progression or relapse by 45% and reduced the risk of death by 47% in this population. There is no direct evidence for the clinical effectiveness of adding rituximab to CHOP in the treatment of DLBCL in those aged 18-59 years, although data from phase I and II trials confirm its safety and efficacy in a preclinical setting. The cost-effectiveness modelling presented here has shown that rituximab in combination with CHOP chemotherapy regimen is likely to be considered a cost-effective treatment for DLBCL when compared with the current standard treatment, CHOP chemotherapy only. Analysis of quality of life (QoL) in the area of NHL is limited and only one cost-utility analysis for the treatment of CHOP in NHL was identified. Both the SCHARR and the manufacturer's models utilised QoL utility scores from an unpublished data source. Further research within this area would help to improve the robustness of QoL utility analysis within DLBCL and also NHL as a whole. Further clinical trials might also establish whether R-CHOP may replace peripheral blood stem cell transplant in high-risk patients and whether the doses of chemotherapy in the elderly may be reduced if rituximab is added to less intensive regimens.

Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

OBJECTIVES: To update an earlier published report reviewing the effectiveness and cost-effectiveness of liquid-based cytology (LBC). DATA SOURCES: Electronic bibliographic databases, relevant articles, sponsor submissions and various health services research-related resources. REVIEW METHODS: The selected data were reviewed and assessed with respect to the quality of the evidence. Pooled estimates of the parameters of interest were derived from the original and the updated studies. Meta-analyses were undertaken where appropriate. The mathematical model developed for the original rapid review of LBC was adapted to synthesise the updated data to estimate costs, survival and quality-adjusted survival of patients tested using LBC and using Papanicolaou (Pap) smear testing. Cost data from published sources were incorporated into the above model to allow economic, as well as clinical, implications of treatment to be assessed. The primary incremental cost-effectiveness ratio is the cost per life year gained (LYG), although estimates of the cost per quality-adjusted life-year (QALY) gained are also presented. A sensitivity analysis was undertaken to identify the key parameters that determine the cost-effectiveness of the treatments, with the objective of identifying how robust the results of the economic analysis are, given the current level of evidence. RESULTS: From the evidence available, it is likely that the LBC technique will reduce the number of false-negative test results. Modelling analyses undertaken as part of this study indicate that this would reduce the incidence of invasive cancer. There is now more evidence to support improvements emanating from the use of LBC screening in terms of a reduced number of unsatisfactory specimens and a decrease in the time needed to obtain the smear samples. The estimated annual gross cost of consumables and operating equipment, and other one-off conversion costs associated with introducing the new technique, will be between 17 British pounds and 38 British pounds million in England and Wales, depending on the LBC system and the configuration of the service. Analyses based on models of disease natural history, conducted in this study, showed that conventional Pap smear screening was extendedly dominated by LBC (LBC was always more cost-effective than conventional Pap smear testing over the same screening interval). Comparing LBC across alternative screening intervals gave a cost-effectiveness of under 10,000 British pounds per LYG when screening was undertaken every 3 years. The cost-effectiveness results were relatively stable under most conditions, although if screening outcomes such as borderline results and colposcopy are assumed to induce even small amounts of disutility then LBC screening at 5-yearly intervals may be the most cost-effective option. CONCLUSIONS: This updated analysis provides more certainty with regard to the potential cost-effectiveness of LBC compared with conventional Pap smear testing. However, there is uncertainty regarding the relative effectiveness (and cost-effectiveness) of the two main LBC techniques. Further research in the area of utility assessment may be worthwhile and possibly a full cost-effectiveness study of LBC based on a trial of its introduction in a low-prevalence population, although the results of the modelling analysis provide a robust argument that LBC is a cost-effective alternative to conventional cervical cancer screening. A randomised comparison of the two main techniques may also be useful.

Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5-fluorouracil/folinic acid (5-FU/FA) regimens. DATA SOURCES: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted. REVIEW METHODS: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5-FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens. RESULTS: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand-foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve health-related quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at 2111 pounds and 3375 pounds, respectively, compared with the total treatment cost for the Mayo regimen of 3579 pounds. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were 3684 pounds and 6155 pounds, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be 1461 pounds and 209 pounds, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be 1353 pounds and 101 pounds, respectively, and over the inpatient de Gramont regimen were estimated to be 4123 pounds and 2870 pounds, respectively. CONCLUSIONS: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data.

Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of new and emerging technologies for early, localised prostate cancer. DATA SOURCES: Electronic databases, reference lists of relevant articles and various health services research-related resources. REVIEW METHODS: A list of new and emerging technologies was identified and agreed. A systematic review was undertaken and selected studies were reviewed against a set of criteria. An economic model was developed and used to compare the specified newer treatments with the traditional approaches. RESULTS: For neoadjuvant hormonal therapy, no evidence of benefit was seen in terms of biochemical disease-free survival. For adjuvant hormonal therapy, there was no evidence of benefit in terms of survival, but some conflicting evidence that higher risk patients may benefit. The largest number of studies reported results for brachytherapy, where some evidence suggested that it may be more effective than standard treatments for lower risk patients, although less effective for intermediate- and high-risk patients, in terms of biochemical disease-free survival. Lower quality evidence reported fewer complications than for standard treatments. Higher quality evidence suggested that disease-specific quality of life (QoL) for brachytherapy patients was lower than for patients receiving standard treatments. The review of three-dimensional conformal radiotherapy (3D-CRT) considered treatment-related morbidity, where significantly fewer gastrointestinal complications occurred than with standard radiotherapy. It was suggested that higher radiation doses achieved better disease control, although patient characteristics were often reported as independent indicators of control. The review of intensity-modulated conformal radiotherapy suggested that late gastrointestinal toxicity may be reduced compared with 3D-CRT. For cryotherapy, high rates of impotence were reported. Owing to the paucity and poor quality of evidence identified for other interventions, conclusions regarding their clinical effectiveness cannot be drawn. Cost-effectiveness estimates were based on the impact of adverse events on quality-adjusted life-years and the assessment was restricted to brachytherapy, 3D-CRT and cryotherapy compared with standard treatments. Of the new treatments included, only cryotherapy appeared not to be potentially cost-effective compared with traditional treatments, owing to the associated high incidence of impotence. CONCLUSIONS: The results of the clinical effectiveness review should be viewed in the context of the quality of the available evidence. Very few randomised controlled trials (RCTs) were identified, with the majority of included studies being descriptive case series, open to patient selection bias and measuring surrogate end-points with short-term follow-up. It is difficult therefore to draw conclusions on the relative benefits or otherwise of the newer technologies owing to the lack of substantive evidence of any quality and the lack of comparisons between the newer technologies and with standard treatments. Given the lack of high-quality clinical evidence with long-term follow-up and the uncertainty surrounding the assumptions in the economic analysis, the following areas are recommended for further research: RCTs with sufficient follow-up to measure benefits in terms of overall survival to include QoL measurement to establish trade-offs between potential adverse events and benefits of treatment; the identification of prognostic risk factors among men diagnosed with early prostate cancer; QoL studies to compare the utility of health states among patients on active monitoring, patients receiving treatment and the comparable healthy population; the relationship between surrogate end-points and survival; and the adoption of standard definitions for adverse events.

The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of machine perfusion (MP) compared to cold storage (CS), as a means of preserving kidneys prior to transplantation. Transplantation of kidneys from both heart-beating donors (HBDs) and non-heart-beating donors (NHBDs) is considered. Finally to review whether the use of MP can allow valid testing of kidney viability prior to transplantation. DATA SOURCES: Fifteen electronic bibliographic databases were searched. The reference lists of relevant articles and sponsor submissions were hand searched and various health service research-related resources were consulted via the Internet. REVIEW METHODS: A literature search was undertaken to identify relevant studies and a meta-analysis performed on the studies that had appropriate comparator groups and reported sufficient data. A structured review examined tests of viability of kidneys on MP. Economic modelling was used to determine the cost-effectiveness and cost-utility of MP. RESULTS: The meta-analysis suggested that the use of MP, as compared with CS, is associated with a relative risk of delayed graft function (DGF) of 0.804 (95% confidence limits 0.672 to 0.961). There was no evidence to suggest that this effect is different in kidneys taken from HBDs as opposed to NHBDs. Meta-analysis of 1-year graft survival data showed no significant effect, but the studies, even when aggregated, were severely underpowered with respect to the likely impact on graft survival. The size of effects demonstrated were in line with those predicted by an indirect model of graft survival based on the association of DGF with graft loss. The economic assessment indicated that it is unlikely that in the UK health setting complete cost recovery will be obtained from a reduction in the incidence of DGF. The probability that MP is cheaper and more effective than CS in the long term was estimated at around 80% for NHBD recipients and 50-60% for HBD recipients. Flow characteristics of the perfusate of kidneys undergoing MP may be an indicator of kidney viability, but data were inadequate to calculate the sensitivity and specificity of any test based on this. The concentration of alpha-glutathione-S-transferase (a marker of cell damage) in the perfusate may be the basis of a valid test. A threshold of 2800 micrograms/100 g gave a sensitivity of 93% and specificity of 33% (and hence a likelihood ratio of 1.41). CONCLUSIONS: The baseline analysis indicated that in the long-term MP would be expected to be cheaper and more effective than CS for both HBD and NHBD recipients. A definitive study of the clinical benefit of MP in order to establish its effect on DGF and longer term graft survival would be valuable, together with an economic evaluation of the benefits. While direct evidence relating to improvements in graft survival would be preferable, the small predicted improvement indicates that a very large sample size would be required. In addition to seeking direct evidence of the impact on DGF, research quantifying the impact of DGF on graft survival in this technology is required. Research is also needed to establish whether a valid test (or combination of tests) of kidney viability can be developed.

Value for the future and preventive health behavior.

Many everyday decisions require trade-offs between immediate and delayed benefits. Although much research has assessed discounting of delayed outcomes by using hypothetical scenarios, little research has examined whether these discounting measures correspond to real-world behavior. Three studies examined the relationship between scenario measures of time preference and preventive health behaviors that require an upfront cost to achieve a long-term benefit. Responses to time preference scenarios showed weak or no relationship to influenza vaccination, adherence to a medication regimen to control high blood pressure, and adherence to cholesterol-lowering medication. The finding that scenario measures of time preference have surprisingly little relationship to actual behaviors exemplifying intertemporal trade-offs places limits on the applications of time preference research to the promotion of preventive health behavior.