The effect of broadening the definition of generalized anxiety disorder on healthcare resource utilization and related costs in outpatient psychiatric clinics

Background: Patients with generalized anxiety disorder (GAD) are among the highest users of healthcare resources. The broadening of the DSM-IV criteria for GAD has been a subject of controversy in the literature, but its consequences have not been analyzed to date. Objective: The purpose of this study was to analyze how the broadening of the DSM-IV criteria affects healthcare resource utilization and related costs. Methods: A multicentre, prospective, observational study was conducted in randomly selected outpatient psychiatric clinics between October 2007 and April 2008. Patients diagnosed according to DSM-IV or broader criteria (1 month of excessive or non-excessive worry and only 2 associated DSM-IV symptoms) for the first time were consecutively enrolled. Socio-demographic data, healthcare resources and corresponding costs were collected over a 6-month period. Results: A total of 3549 patients were systematically recruited, 1815 in the DSM-IV criteria group (DG) and1264 inthe broad criteria group (BG). Treatments prescribed were similar for antidepressants in both groups (77.0% in the DG vs. 75.3% in the BG, p = 0.284), and slightly higher in the DG for benzodiazepines (71.5% vs. 67.2% respectively, p = 0.011) and anticonvulsants (72.1% vs. 67.0% respectively, p = 0.002). Healthcare resource utilization was statistically reduced to a similar extent in both groups as a consequence of treatment, yielding a reduction in the cost of illness of €1196 (SD = 1158) and €1112 (SD = 874) respectively;p = 0.304, over a 6-month period. Conclusion: The broadening of the GAD criteria could lead to earlier diagnosis not necessarily associated with an increase in healthcare resource utilization or costs to the National Health System in the six-month follow-up.

Epidemiology and natural history of hepatitis C virus infection

Hepatitis C virus(HCV)affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma.Globally,at least one third of hepatocellular carcinoma cases are attributed to HCV infection,and 350000 people died from HCV related diseases per year.There is a great geographical variation of HCV infection globally,with risk factors for the HCV infection differing in various countries.The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations.A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma,and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma.However,prospective cohorts comprising individuals with HCV infection are still uncommon.The risk evaluation of viral load elevation and associated liver disease/cancer in HCV(REVEAL-HCV)study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years.Most of them have acquired HCV infection through iatrogenic transmission routes.As the participants in the REVEALHCV study rarely receive antiviral therapies,it provides a unique opportunity to study the natural history of chronic HCV infection.In this review,the prevalence,risk factors and natural history of HCV infection are comprehensively reviewed.The study cohort,data collection,and findings on liver disease progression of the REVEAL-HCV study are described.

iStent inject? and cataract surgery for mild-to-moderate primary open angle glaucoma in Japan: a cost-utility analysis

AIM: To evaluate the cost-utility of iStent inject;with cataract surgery vs cataract surgery alone in patients with mild-to-moderate primary open angle glaucoma(POAG) in the Japanese setting from a public payer’s perspective.METHODS: A Markov model was adapted to estimate the cost-utility of iStent inject;plus cataract surgery vs cataract surgery alone in one eye in patients with mild-tomoderate POAG over lifetime horizon from the perspective of Japanese public payer. Japanese sources were used for patients’ characteristics, clinical data, utility, and costs whenever available. Non-Japanese data were validated by Japanese clinical experts. RESULTS: In the probabilistic base case analysis, iStent inject;with cataract surgery was found to be cost-effective compared with cataract surgery alone over a lifetime horizon when using the ￥5 000 000/quality-adjusted life year(QALY)willingness-to-pay threshold. The incremental cost-utility ratio(ICUR) was estimated to be ￥1 430 647/QALY gained and the incremental cost-utility ratio(ICER) was estimated to be ￥12 845 154/blind eye avoided. iStent inject;with cataract surgery vs cataract surgery alone was found to increase costs(￥1 025 785 vs ￥933 759, respectively) but was more effective in increasing QALYs(12.80 vs 12.74) and avoiding blinded eyes(0.133 vs 0.141). The differences in costs were mainly driven by costs of primary surgery(￥279 903 vs ￥121 349). In the scenario analysis from a societal perspective, which included caregiver burden, iStent inject;with cataract surgery was found to dominate cataract surgery alone.CONCLUSION: The iStent inject;with cataract surgery is a cost-effective strategy over cataract surgery alone from the public payer’s perspective and cost-saving from the societal perspective in patients with mild-to-moderate POAG in Japan.

Effect of antihypertensive therapy on hospitalization and mortality among uncomplicated and high risk hypertensive patients

Objective: Evaluate the impact of antihypertensive drugs (AHD) on stroke and acute myocardial infarction (AMI) and death for 3 cohorts of patients: diabetics, high risk, and hypertensive. Methods: This was a retrospective cohort obervational study based on administrative database of 7 Italian Local Health Units. Newly treated patients with AHD were enrolled from 01/01/2004 to 06/30/2007. Drug utilization and incidence of death, stroke and AMI were measured until 12/31/2007. Results: The study enrolled 125,770 patients aged ≥ 18-year-old: 8516 diabetic, 8549 high risk, and 108,705 hypertensive. Diabetic and high risk patients were more frequently male (57.2%, 64.9% VS 46.6%) and older (66.4 ± 11.6, 67.5 ± 13.2 VS 61.6 ± 13.9) than hypertensive patients and were more treated with concomitant therapy. Drugs acting on the renin-angiotensin system were the more fre- quent choice in the three cohorts but with a dif- ferent prevalence (63.9%, 52.9%, 35.9% in dia- betic, hypertensive and high risk patients re- spectively). Adherent patients to AHD > 80% were 44.0% among diabetic patients, 48.4% among high risk, 35.2% among hypertensive. A Cox regression model showed that the risk of the combined outcome was determined by increasing age, male gender, presence of concomitant therapy, low adherence to AHD and first choice of AHD. Conclusions: An integrated analysis of prescription and hospital admission database has the great advantage that it uses routinely available data, it can be done quickly and by few staff, and it is less expensive than planned large scale survey.

A Real-World Observational Study of Patients with Advanced Melanoma Receiving First-Line Ipilimumab in a Community Practice Setting

Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced melanoma (AM) patients treated with first-line ipilimumab in realworld US community practice. Methods: Adult patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between April 2011 and September 2012 were retrospectively identified at US Oncology sites. Clinical data were abstracted from patient medical records. Results: Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9% of patients had an ECOG performance status of 0 or 1;54.1% were stage M1c;34.4% had brain metastases;24.8% had elevated lactate dehydrogenase, and 13.4% were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by 55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0), median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were experienced by 63.7% of patients. The most frequent AEs were gastrointestinal (41.4%;diarrhea in 19.1%) and skin-related (28.0%;rash in 17.8%);17.8% of patients had an AE that led to ipilimumab discontinuation. Conclusions: These real-world results are consistent with those from clinical trials and provide evidence supporting the effectiveness and safety of first-line ipilimumab 3 mg/kg monotherapy in patients with AM treated in a community practice setting.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn’s disease in the USA

Background:Patients with inflammatory bowel disease(IBD)are at increased risk of herpes zoster(HZ).We evaluated the incidence of HZ in ulcerative colitis(UC)and Crohn’s disease(CD)patients and compared this with HZ incidence in a non-IBD population.Methods:We conducted a retrospective cohort study(GSK study identifier:VEO-000043)of adults aged18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020.Crude HZ incidence rates/1,000 person-years(PY)were calculated,and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models.Results:The study population comprised a total of 29,928 UC,25,959 CD,and 11,839,329 non-IBD patients.Crude overall HZ incidence rates were 13.64/1,000 PY(UC),15.94/1,000 PY(CD),and 7.95/1,000 PY(non-IBD).UC and CD patients had increased HZ incidence rates,with adjusted incidence rate ratios of 1.35(95%confidence interval[CI],1.26–1.44)and 1.66(95%CI,1.56–1.77),respectively,compared with non-IBD patients.Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients.HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate,TNF-inhibitors,or corticosteroids than in UC and CD patients who did not take those medicines.Conclusion:UC and CD patients had increased HZ incidence rates compared with patients without IBD,demonstrating the importance of HZ prevention in IBD patients.

Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America,Europe and Asia:A real-world data analysis

Background:This study examined real-world treatment and management of bacillus Calmette-Guérin(BCG)-unresponsive patients across 3 continents,including patients unable or unwilling to undergo cystectomy.Materials and methods:Physicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy(in Japan,physicians provided a total of 5 patients across both cohorts).Results:Most patients had received 1(37%)or 2(24%)maintenance courses of BCG.Five or more maintenance BCG courses were received by patients in Japan(59%)and China(31%),while in Germany 76%of patients received only 1 course.Most patients became BCG-unresponsive during their first(44%)or second(22%)treatment course;in Germany,77%became BCG-unresponsive during their first treatment course.Most countries did not provide another course of BCG after a patient first became unresponsive,whereas unresponsive patients in Japan and China were most likely to be retreated with BCG."Untreated-on watch and wait"was the main treatment/management approach received post-BCG treatment for 42%or more of patients in most countries except China(39%)and the United States(36%)."Following treatment guidelines"was consistently the top reason for post-BCG treatment selection across all treatment options.Conclusions:This study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer,and found that many patients experienced periods of no treatment after not responding to BCG therapy.

利伐沙班预防全膝关节置换术后静脉血栓栓塞症的成本-效果研究

目的:评估利伐沙班预防人工全膝关节置换术后静脉血栓栓塞症的成本与效果。方法:应用决策树(急性期)和Markov模型(长期)分析与比较利伐沙班与依诺肝素预防人工全膝关节置换术后静脉血栓栓塞症的成本与效果。结果:基础病例分析结果显示利伐沙班明显占优。模型预测利伐沙班治疗组病人比依诺肝素组病人5年内可额外增加0.0019质量调整生命年(QALY),且节省242元。此外,治疗与静脉血栓栓塞症相关并发症的费用利伐沙班组为581元,依诺肝素组则为1059元。概率敏感性分析结果显示当支付意愿阈值为20000元/QALY时,约90%以上患者认为利伐沙班较依诺肝素更具成本-效果。结论:实施人工全膝关节置换术病人若术后服用利伐沙班,其预防静脉血栓栓塞症的效果优于依诺肝素。