The management of sepsis has substantially improved over the past 15 years. In this study, early, goal-directed therapy, which focuses on the initial resuscitation efforts, was compared with usual ...care for the management of severe sepsis in the United Kingdom.
The incidence of severe sepsis and septic shock in adults is estimated to range from 56 to 91 per 100,000 population per year.
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Affected patients have high rates of death, complications, and resource utilization.
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Since 2002, the Surviving Sepsis Campaign (SSC) has promoted best practice, including early recognition, source control, appropriate and timely antibiotic administration, and resuscitation with intravenous fluids and vasoactive drugs.
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Resuscitation guidance is largely based on a 2001 single-center, proof-of-concept study by Rivers et al., which indicated that protocolized delivery of 6 hours of early, goal-directed therapy (EGDT) to patients presenting to the emergency department . . .
•First study to evaluate the economic burden of TRD in the province of Ontario.•Patients with TRD contribute a considerable burden to the healthcare system.•Patients with TRD incurred higher ...healthcare costs compared to Non-MDD patients.•Patients with TRD had more outpatient, primary care provider and psychiatry visits.•The study findings highlight an unmet need for new cost-effective therapies.
The burden of treatment-resistant depression (TRD) in Canada requires empirical characterization to better inform clinicians and policy decision-making in mental health. Towards this aim, this study utilized the Institute for Clinical Evaluative Sciences (ICES) databases to quantify the economic burden and resource utilization of Patients with TRD in Ontario.
TRD, Non-TRD Major Depressive Disorder (Non-TRD MDD) and Non-MDD cohorts were selected from the ICES databases between April 2006-March 2015 and followed-up for at least two years. TRD was defined as a minimum of two treatment failures within one-year of the index MDD diagnosis. Non-TRD and Non-MDD patients were matched with patients with TRD to analyze costs, resource utilization, and demographic information.
Out of 277 patients with TRD identified, the average age was 52 years (SD 16) and 53% were female. Compared to Non-TRD, the patients with TRD had more all-cause visits to outpatient (38.2 vs. 24.2) and emergency units (2.7 vs. 2.0) and more depression-related visits to GPs (3.06 vs. 1.63) and psychiatrists (5.88 vs. 1.95) (all p < 0.05). The average two-year cost for TRD patients was $20,998 (CAD).
This study included patients with only public plan coverage; therefore, overall TRD population and cash and private claims were not captured.
Patients with TRD exhibit a significantly higher demand on healthcare resources and higher overall payments compared to Non-TRD patients. The findings suggest that there are current challenges in adequately managing this difficult-to-treat patient group and there remains a high unmet need for new therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Real‐world clinical effectiveness of liraglutide 3.0 mg, in combination with diet and exercise, was investigated 4 and 6 months post initiation. Changes in absolute and percent body weight ...were examined from baseline.
Methods
A cohort of liraglutide 3.0 mg initiators in 2015 and 2016 was identified from six Canadian weight‐management clinics. Post initiation values at 4 and 6 months were compared with baseline values using a paired t test.
Results
The full cohort consisted of 311 participants, with 210 in the ≥ 4‐month persistence group and 167 in the ≥ 6‐month persistence group. Average baseline BMI was 40.7 kg/m2, and weight was 114.8 kg. There was a significant change in body weight 6 and 4 months after initiation of treatment in persistent subjects (≥ 6‐month: −8.0 kg, P < 0.001; ≥ 4‐month: −7.0 kg, P < 0.001) and All Subjects, regardless of persistence (−7.3 kg; P < 0.001). Percentage change in body weight from baseline was −7.1% in the ≥ 6‐month group and −6.3% in the ≥ 4‐month group, and All Subjects lost 6.5% body weight. Of participants in the ≥ 6‐month group, 64.10% and 34.5% lost ≥ 5% and > 10% body weight, respectively.
Conclusions
In a real‐world setting, liraglutide 3.0 mg, when combined with diet and exercise, was associated with clinically meaningful weight loss.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The economic impact of perianal fistulas in Crohn’s disease (CD) has not been formally assessed in population-based studies in the biologic era.
Aim
To compare direct health care costs in ...persons with and without perianal fistulas.
Methods
We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive “cases” were matched to up to 4 “controls” with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls.
Results
A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater).
Conclusion
In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty ...remains over its clinical effectiveness and cost-effectiveness.
The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness.
A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation.
Fifty-six NHS hospitals in England.
A total of 1260 patients who presented at EDs with septic shock.
EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1.
All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year.
Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 (95% CI -£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events.
Recruitment was lower at weekends and out of hours. The intervention could not be blinded.
There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%.
The ProMISe (Protocolised Management In Sepsis) trial completes the planned trio of evaluations of EGDT across the USA, Australasia and England; all have indicated that EGDT is not superior to usual resuscitation. Recognising that each of the three individual, large trials has limited power for evaluating potentially important subgroups, the harmonised approach adopted provides the opportunity to conduct an individual patient data meta-analysis, enhancing both knowledge and generalisability.
Current Controlled Trials ISRCTN36307479.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 97. See the NIHR Journals Library website for further project information.
Objectives
To assess real‐world effectiveness, safety, and usage of erenumab in Canadian patients with episodic and chronic migraine with prior ineffective prophylactic treatments.
Background
In ...randomized controlled trials, erenumab demonstrated efficacy for migraine prevention in patients with ≤4 prior ineffective prophylactic migraine therapies. The “Migraine prevention with AimoviG: Informative Canadian real‐world study” (MAGIC) assessed real‐world effectiveness of erenumab in Canadian patients with migraine.
Methods
MAGIC was a prospective open‐label, observational study conducted in Canadian patients with chronic migraine (CM) and episodic migraine (EM) with two to six categories of prior ineffective prophylactic therapies. Participants were administered 70 mg or 140 mg erenumab monthly based on physician’s assessment. Migraine attacks were self‐assessed using an electronic diary and patient‐reported outcome questionnaires. The primary outcome was the proportion of subjects achieving ≥50% reduction in monthly migraine days (MMD) after the 3‐month treatment period.
Results
Among the 95 participants who mostly experienced two (54.7%) or three (32.6%) prior categories of ineffective prophylactic therapies and who initiated erenumab, treatment was generally safe and well tolerated; 89/95 (93.7%) participants initiated treatment with 140 mg erenumab. At week 12, 32/95 (33.7%) participants including 17/64 (26.6%) CM and 15/32 (48.4%) EM achieved ≥50% reduction in MMD while 30/86 (34.9%) participants including 19/55 (34.5%) CM and 11/31 (35.5%) EM achieved ≥50% reduction in MMD at week 24. Through patient‐reported outcome questionnaires, 62/95 (65.3%) and 45/86 (52.3%) participants reported improvement of their condition at weeks 12 and 24, respectively. Physicians observed improvement in the condition of 78/95 (82.1%) and 67/86 (77.9%) participants at weeks 12 and 24, respectively.
Conclusion
One‐third of patients with EM and CM achieved ≥50% MMD reduction after 3 months of erenumab treatment. This study provides real‐world evidence of erenumab effectiveness, safety, and usage for migraine prevention in adult Canadian patients with multiple prior ineffective prophylactic treatments.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To describe the real‐world treatment persistence (defined as the continuation of medication for the prescribed treatment duration), demographics and clinical characteristics, and treatment ...patterns for patients prescribed erenumab for migraine prevention in Canada.
Background
The effectiveness of prophylactic migraine treatments is often undermined by poor treatment persistence. In clinical trials, erenumab has demonstrated efficacy and tolerability as a preventive treatment, but less is known about the longer term treatment persistence with erenumab.
Methods
This is a real‐world retrospective cohort study where a descriptive analysis of secondary patient data was conducted. Enrollment and prescription data were extracted from a patient support program for a cohort of patients prescribed erenumab in Canada between September 2018 and December 2019 and analyzed for persistence, baseline demographics, clinical characteristics, and treatment patterns. Descriptive analyses and unadjusted Kaplan–Meier (KM) curves were used to summarize the persistence and dose escalation/de‐escalation at different timepoints.
Results
Data were analyzed for 14,282 patients. Median patient age was 47 years, 11,852 (83.0%) of patients were female, and 9443 (66.1%) had chronic migraine at treatment initiation. Based on KM methods, 71.0% of patients overall were persistent to erenumab 360 days after treatment initiation. Within 360 days of treatment initiation, it is estimated that 59.3% (KM‐derived) of patients who initiated erenumab at 70 mg escalated to 140 mg, and 4.4% (KM‐derived) of patients who initiated at 140 mg de‐escalated to 70 mg.
Conclusions
The majority of patients prescribed erenumab remained persistent for at least a year after treatment initiation, and most patients initiated or escalated to a 140 mg dose. These results suggest that erenumab is well tolerated, and its uptake as a new class of prophylactic treatment for migraine in real‐world clinical practice is not likely to be undermined by poor persistence when coverage for erenumab is easily available.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ObjectiveTo understand the association of seizure frequency with healthcare resource utilisation (HCRU) and mortality in UK children with epilepsy (CWE).DesignRetrospective cohort ...study.SettingRoutinely collected data in primary care from The Health Improvement Network UK database.PatientsCWE ≥1 and<18 years of age with a record of seizure frequency were included in mortality analyses from 2005 to 2015 and HCRU analyses from 2010 to 2015.Main outcome measuresFrequency of HCRU contacts during the year following latest seizure frequency and mortality (descriptive and Cox proportional hazards regression) from first record of seizure frequency.ResultsHigher seizure frequency was related to increased HCRU utilisation and mortality. In negative binomial regression, each category increase in seizure frequency related to 11% more visits to general practitioners, 35% more inpatient admissions, 15% more outpatient visits and increased direct HCRU costs (24%). 11 patients died during 12 490 patient-years follow-up. The unadjusted HR of mortality per higher category of seizure frequency was 2.56 (95% CI: 1.52 to 4.31). Adjustment for age and number of prescribed anti-epileptic drugs at index attenuated this estimate to 2.11 (95% CI: 1.24 to 3.60).ConclusionHigher seizure frequency is associated with greater HCRU and mortality in CWE in the UK. Improvement in seizure control may potentially lead to better patient outcomes and reduced healthcare use.
The present study was designed to (1) establish current sedation practice in UK critical care to inform evidence synthesis and potential future primary research and (2) to compare practice reported ...via a survey with actual practice assessed in a point prevalence study (PPS).
UK adult general critical care units were invited to participate in a survey of current sedation practice, and a representative sample of units was invited to participate in a PPS of sedation practice at the patient level. Survey responses were compared with PPS data where both were available.
Survey responses were received from 214 (91 %) of 235 eligible critical care units. Of these respondents, 57 % reported having a written sedation protocol, 94 % having a policy of daily sedation holds and 94 % using a sedation scale to assess depth of sedation. In the PPS, across units reporting a policy of daily sedation holds, a median of 50 % (IQR 33-75 %) of sedated patients were considered for a sedation hold. A median of 88 % (IQR 63-100 %) of patients were assessed using the same sedation scale as reported in the survey. Both the survey and the PPS indicated propofol as the preferred sedative and alfentanil, fentanyl and morphine as the preferred analgesics. In most of the PPS units, all patients had received the unit's reported first-choice sedative (median across units 100 %, IQR 64-100 %), and a median of 80 % (IQR 67-100 %) of patients had received the unit's reported first-choice analgesic. Most units (83 %) reported in the survey that sedatives are usually administered in combination with analgesics. Across units that participated in the PPS, 69 % of patients had received a combination of agents - most frequently propofol combined with either alfentanil or fentanyl.
Clinical practice reported in the national survey did not accurately reflect actual clinical practice at the patient level observed in the PPS. Employing a mixed methods approach provided a more complete picture of sedation practice in terms of breadth and depth of information.
Why try to predict ICU outcomes? Power, G Sarah; Harrison, David A
Current opinion in critical care,
10/2014, Volume:
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Journal Article
To describe why the prediction of ICU outcomes is essential to underpin critical care quality improvement programmes.
Recent literature demonstrates that risk-adjusted mortality is a widely used and ...well-accepted quality indicator for benchmarking ICU performance. Ongoing research continues to address the best ways to present the results of benchmarking through either direct comparison among institutions (e.g., by funnel plots) or indirect comparison against the risk predictions from a risk model (e.g., by process control charts). There is also ongoing research and debate regarding event-based outcomes (e.g., hospital mortality) versus time-based outcomes (e.g., 30-day mortality). Beyond benchmarking, ICU outcome prediction models have a role in risk adjustment and risk stratification in randomized controlled trials, and adjusting for confounding in nonrandomized, observational research. Recent examples include comparing risk-adjusted outcomes according to 'capacity strain' on the ICU and extending propensity matching methods to evaluate outcomes of patients managed with a pulmonary artery catheter, among others. Risk models may have a role in communicating risk, but their utility for individual patient decision-making is limited.
Risk-adjusted mortality has strong support from the critical care community as a quality indicator for benchmarking ICU performance but is dependent on up-to-date, accurate risk models. ICU outcome prediction can also contribute to both randomized and nonrandomized research and potentially contribute to individual patient management, although generic risk models should not be used to guide individual treatment decisions.
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