Long-Term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-Based Study.

INTRODUCTION: Healthcare costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease, are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and preexisting (PE) MG in Sweden. METHODS: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥24-month follow-up during the period January 1, 2010, to December 31, 2017, were included. RESULTS: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years, and 52.3% were female. In the first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs. 83.9%), corticosteroids (59.6% vs. 45.8%), thymectomy (12.1% vs. 0.7%), and plasma exchange (3.8% vs. 0.6%); had higher all-cause (70.9% vs. 35.8%) and MG-related (62.5% vs. 18.4%) hospitalization rates with 11 more hospitalization days (all p < 0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred EUR 7,302 (p < 0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p < 0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ∼55% for ND MG from year 1 and were comparable with PE MG. CONCLUSION: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies, and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality.

BACKGROUND: Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission. METHODS: Post hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined. RESULTS: The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up. CONCLUSION: Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).

A Comparative Study on the Effects of Different Sources of Carboxymethyl Poria Polysaccharides on the Repair of DSS-Induced Colitis in Mice.

Carboxymethyl poria polysaccharide plays important anti-tumor, antioxidant, and anti-inflammatory roles. Therefore, this study aimed to compare the healing impacts of two different sources of carboxymethyl poria polysaccharides [Carboxymethylat Poria Polysaccharides I (CMP I) and Carboxymethylat Poria Polysaccharides II (CMP II)] on ulcerative colitis in mice caused by dextran sulfate sodium (DSS). All the mice were arbitrarily split into five groups (n = 6): (a) control (CTRL), (b) DSS, (c) SAZ (sulfasalazine), (d) CMP I, and (e) CMP II. The experiment lasted for 21 days, and the body weight and final colon length were monitored. A histological analysis of the mouse colon tissue was carried out using H&E staining to assess the degree of inflammatory infiltration. The levels of inflammatory cytokines [interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4)] and enzymes [superoxide dismutase (SOD) and myeloperoxidase (MPO)] in the serum were examined using ELISA. Additionally, 16S ribosomal RNA sequencing was used to analyze the microorganisms in the colon. The results indicated that both CMP I and CMP II alleviated weight loss, colonic shortening, and inflammatory factor infestation in colonic tissues caused by DSS (p < 0.05). Furthermore, the ELISA results revealed that both CMP I and CMP II reduced the expression of IL-1ß, IL-6, TNF-α, and MPO, and elevated the expression of IL-4 and SOD in the sera of the mice (p < 0.05). Moreover, 16S rRNA sequencing showed that CMP I and CMP II increased the plenitude of microorganisms in the mouse colon relative to that in the DSS group. The results also indicated that the therapeutic effect of CMP I on DSS-induced colitis in the mice was superior to that of CMP II. This study demonstrated that carboxymethyl poria polysaccharide from Poria cocos had therapeutic effects on DSS-induced colitis in mice, with CMP I being more effective than CMP II.

Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study.

BACKGROUND: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. METHODS: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). RESULTS: A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p < .0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p < .0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p < 0.05). CONCLUSION: Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.

Effect of the Combination of Clostridium butyricum and Mycelium of Phellinus igniarius on Intestinal Microbiota and Serum Metabolites in DSS-Induced Colitis.

Clostridium butyricum (CB) and Phellinus igniarius (PI) have anti-inflammatory, immune regulation, anti-tumor, and other functions. This study aimed to explore the therapeutic effect of CB and mycelium of PI (MPI) alone and in combination on colitis mice induced by dextran sodium sulfate (DSS). Mice were randomly assigned to five groups: (1) control (CTRL), (2) DSS, (3) CB, (4) MPI, and (5) CB + MPI (CON). The weight of the mice was recorded daily during the experiment, and the length of the colon was measured on the last day of the experiment. The colons were collected for hematoxylin and eosin staining, colon contents were collected for intestinal flora analysis, and serum was collected for metabolite analysis. The results showed that compared with the DSS group, CB, MPI, and CON treatments inhibited the weight loss and colon length shortening caused by DSS, significantly increased the concentrations of interleukin (IL)-4, IL-10, and superoxide dismutase, and significantly decreased the concentrations of IL-6, tumor necrosis factor-α, and myeloperoxidase. Gene sequence analysis of 16S rRNA showed that CB, MPI, and CON treatments changed the composition and structure of intestinal microorganisms. Metabolome results showed that CB, MPI, and CON treatments changed serum metabolites in DSS-treated mice, including dodecenoylcarnitine, L-urobilinogen, and citric acid. In conclusion, CB, MPI, and CON treatments alleviated DSS-induced colitis in mice by regulating intestinal flora and metabolites, with the CON group having the best effect.

Structural characterization of extracellular polysaccharides from Phellinus igniarius SH-1 and their therapeutic effects on DSS induced colitis in mice.

Phellinus igniarius is a valuable medicinal and edible mushroom, and its polysaccharides exhibit excellent anti-inflammatory activity. During liquid fermentation to produce P. igniarius mycelia, the fermentation liquid is often discarded, but it contains extracellular polysaccharides. To better utilize these resources, P. igniarius SH-1 was fermented in a 100 L fermenter, and PIPS-2 was isolated and purified from the fermentation broth. The structural characteristics and anti-inflammatory activity of PIPS-2 were determined. PIPS-2 had a molecular weight of 22.855 kDa and was composed of galactose and mannose in a molar ratio of 0.38:0.62. Structural analysis revealed that the main chain of PIPS-2 involved →2)-α-D-Manp-(1 â†’ 3)-ß-D-Galf-(1→, and the side chains involved α-D-Manp-(1 â†’ 6)-α-D-Manp-(1→, α-D-Manp-(1 â†’ 3)-α-D-Manp-(1→, and α-D-Manp-(1. PIPS-2 alleviated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice, improved the imbalance of inflammatory factors and antioxidant enzymes, and increased short-chain fatty acid contents. Combining the intestinal flora and metabolite results, PIPS-2 was found to regulate the abundance of Firmicutes, Lachnospiraceae_NK4A136_group, Proteobacteria, Bacteroides, and many serum metabolites including hexadecenal, copalic acid, 8-hydroxyeicosatetraenoic acid, artepillin C, and uric acid, thereby ameliorating metabolite related disorders in mice with colitis. In summary, PIPS-2 may improve colitis in mice by regulating the gut microbiota and metabolites.

The impact of diagnosis delay on European patients with generalised myasthenia gravis.

OBJECTIVE: The objective was to determine the mean duration of diagnosis delay for patients with myasthenia gravis from five European countries and explore the impact of >1 year diagnosis delay. METHODS: Patients with myasthenia gravis (N = 387) from Europe (France/Germany/Italy/Spain/United Kingdom) and their physicians participated in the Adelphi Real World Myasthenia Gravis Disease Specific Programme™. Diagnosis delay (time from symptom onset to diagnosis) was calculated and characteristics described for patients experiencing >1 year and ≤1 year diagnosis delay. Denominators varied according to outcome as missing data were not imputed. RESULTS: Mean (standard deviation) diagnosis delay was 363.1 (520.9) days, and 27.1% (105 out of 387) of patients experienced diagnosis delay >1 year. Among patients with >1 year and ≤1 year diagnosis delay, respectively, 69.2% (72 out of 104) and 17.4% [45 out of 259] had initially received a different diagnosis (physician-reported); 40.0% (42 out of 105) and 24.1% (68 out of 282) were Myasthenia Gravis Foundation of America class III at the time of the survey (physician-reported); 72.4% (76 out of 105) and 61.3% (173 out of 282) had fatigue (subjective physician reporting from a pre-selected list of symptoms); 30.5% (32 out of 105) and 17.4% (49 out of 282) had anxiety and 21.9% (23 out of 105) and 13.1% (37 out of 282) had depression (both subjective physician reporting from a pre-selected list, Likert-style); and mean (standard deviation) MG-QoL-15r score was 14.4 (5.50) and 12.6 (7.84) (self-reported by N = 43 and N = 74 patients, respectively). INTERPRETATION: More than a quarter of patients with myasthenia gravis experienced diagnosis delay of >1 year. These patients had a different clinical profile with regards to severity, symptoms, comorbidities and MG-QoL-15r score, compared with patients experiencing ≤1 year diagnosis delay.

Burden of peripheral arterial disease in Europe and the United States: a patient survey.

BACKGROUND: The aim of the current study was to quantify the burden of peripheral arterial disease (PAD) with respect to health-related quality of life, work productivity and activity impairment, and healthcare resource utilization. METHODS: Data were obtained from the 2010 EU National Health and Wellness Survey (NHWS), which included participants from France, Germany, Italy, Spain, and the UK (5 EU, N = 57,805) as well as the 2010 US NHWS (N = 75,000). The NHWS is an annual, cross-sectional, self-administered Internet survey which employs a stratified random sampling frame to match the age and gender characteristics of the NHWS sample with known population statistics. Participants who self-reported a diagnosis of PAD were compared with participants who did not self-report a diagnosis of PAD on health-related quality of life (mental and physical component summary scores and health utilities from the Short Form-12v2), work productivity and activity impairment (Work Productivity and Activity Impairment questionnaire), and healthcare resource use in terms of the number of physician visits, emergency room visits, and hospitalizations in the past six months through regression modeling adjusting for demographics and health characteristics. RESULTS: A total of 743 (1.29%) and 777 (1.04%) participants self-reported a diagnosis of PAD in the 5 EU and US, respectively. After adjusting for demographics and health characteristics, patients with PAD reported worse health-related quality of life, as measured by health utilities (5 EU: 0.66 vs. 0.70; US: 0.66 vs. 0.72; all p < .05), greater overall work impairment percentage (5 EU: 38.27% vs. 27.48%; US: 23.89% vs. 14.26%) and greater healthcare resource use compared to participants without PAD (all p < .05). CONCLUSIONS: These results suggest a significant burden for patients with PAD in both the 5 EU countries and the US with respect to both quality of life and economic outcomes. Improved management of these patients may have profound effects from both patient and societal perspectives.

Use of Clinical Global Impressions-Severity (CGI-S) to Assess Response to Antidepressant Treatment in Patients with Treatment-Resistant Depression.

Background: This post-hoc analysis evaluated the agreement between Clinical Global Impressions-Severity (CGI-S) score- and Montgomery-Åsberg Depression Rating Scale (MADRS) total score-based assessment of response in patients with treatment-resistant depression (TRD) treated with esketamine nasal spray plus a newly initiated oral antidepressant (ESK-NS + AD). Methods: Data were analyzed from a phase 3, randomized, double-blind study (TRANSFORM-2) of flexibly dosed esketamine or placebo nasal spray plus a newly initiated oral-AD in adults with moderate-to-severe TRD. Patients with ≥50% reduction in MADRS from baseline at the end of the 4-week acute treatment phase were defined as responders. For the CGI-S-based assessment of response, patients with ≥2 points decrease from baseline or a CGI-S score of ≤3 (mildly depressed to normal) were considered responders. Cohen's kappa coefficient was calculated to assess level of agreement between MADRS and CGI-S-based assessments. Results: At the end of 4-week treatment, the proportion of responders among all study patients (n=201) was similar when assessed using the MADRS (61%) and CGI-S (62%) methods, with substantial agreement (Cohen's kappa=0.76; sensitivity=92%; specificity=84%) between both methods. When restricting analysis to ESK-NS + AD-treated patients (n=101) who had a higher response rate (on MADRS: 69%; on CGI-S: 68%), the agreement remained substantial (Cohen's kappa=0.75; sensitivity=91%; specificity=84%). Conclusion: The CGI-S may be a practical and reliable alternative to the MADRS to assess response to ESK-NS + AD in patients with TRD and can be used in real-world practice to support informed treatment decisions.

Patient profiles, initial hospital encounter characteristics, and hospital re-encounters of patients with a hospital emergency department visit or inpatient admission for major depressive disorder.

OBJECTIVES: To gain a better understanding of the characteristics of patients with a hospital encounter for major depressive disorder (MDD) and evaluate associated hospital resource utilization, hospital charges and costs, and hospital re-encounters. METHODS: Adult patients with a hospital encounter (i.e. emergency department [ED] visit only or inpatient admission) with MDD as the primary discharge diagnosis (index event) during July 2018‒March 2019 were selected from the Premier Healthcare Database. Patient characteristics, hospital resource utilization, and hospital charges and costs were evaluated during index events. During a 12-month follow-up, hospital re-encounters (MDD-related and all-cause ED visit only or inpatient readmissions) were examined. RESULTS: The study population included 77,178 patients with an index hospital encounter (ED visit only: 49.9%; inpatient admission: 50.1%) for MDD. The most common secondary mental health-related diagnosis was suicidal ideation/behavior, which was recorded in 51.8% of patients. The mean age was 38.2 years, 53.0% were female, and 72.1% were Caucasian. Among patients with an ED visit only, the mean index hospital charges and costs were $3,608 and $639, respectively. Among those with inpatient admissions, the mean length of stay was 4.9 days, and the mean index hospital charges and costs were $17,107 and $6,095, respectively. During the 12-month follow-up, 13.3% of patients in the overall study population had an MDD-related hospital re-encounter (primary or secondary discharge diagnosis code indicating MDD); nearly one-third (31.3%) occurred within 30 days post-discharge. During the follow-up, 28.1% had an all-cause hospital re-encounter with 29.7% having occurred within 30 days post-discharge. LIMITATIONS: Due to constraints of the Premier Healthcare Database, healthcare resource utilization and costs outside of the hospital could not be evaluated. CONCLUSIONS: Patients with a hospital encounter for MDD are relatively young, commonly have suicidal ideation/behavior, utilize substantial hospital resources, and have a high risk for a hospital re-encounter in the 30 days post-discharge.

Reasons given by general practitioners for non-treatment decisions in younger and older patients with newly diagnosed type 2 diabetes mellitus in the United Kingdom: a survey study.

BACKGROUND: Older patients with newly diagnosed type 2 diabetes mellitus are less likely to receive antihyperglycaemic therapy compared to their younger counterparts. The purpose of this study was to assess the reasons of general practitioners (GPs) for not treating younger and older patients with newly diagnosed type 2 diabetes mellitus with antihyperglycaemic agents. METHODS: In a survey conducted between November 2009 and January 2010, 358 GPs from the United Kingdom selected reasons for not initiating antihyperglycaemic therapy in younger (< 65 years) and older (≥65 years) patients with newly diagnosed type 2 diabetes mellitus and untreated with any antihyperglycaemic agent for at least six months following diagnosis. Thirty-six potential reasons were classified into four major categories: Mild hyperglycaemia, Factors related to antihyperglycaemic agents, Comorbidities and polypharmacy, and Patient-related reasons. Reasons for non-treatment were compared between younger (n = 1, 023) and older (n = 1, 005) patients. RESULTS: Non-treatment reasons related to Mild hyperglycaemia were selected more often by GPs for both younger (88%) and older (86%) patients than those in other categories. For older patients, Factors related to antihyperglycaemic agents (46% vs. 38%) and Comorbidities and polypharmacy (33% vs. 19%), both including safety-related issues, were selected significantly (p < 0.001) more often by GPs. No between-group difference was observed for the Patient-related reasons category. The GP-reported HbA1c threshold for initiating antihyperglycaemic therapy was significantly (p < 0.001) lower for younger patients (mean ± standard deviation: 7.3% ± 0.7) compared to older patients (7.5% ± 0.9). CONCLUSIONS: GPs selected reasons related to Mild hyperglycaemia for non-treatment of their untreated patients with newly diagnosed type 2 diabetes mellitus, despite nearly one-third of these patients having their most recent HbA1c value ≥7%. The findings further suggest that safety-related issues may influence the non-treatment of older patients with type 2 diabetes mellitus.

Suboptimal persistence with inhaled corticosteroid monotherapy among children with persistent asthma in the UK.

BACKGROUND: Long-term studies indicate that adherence to asthma controller therapy decreases over time, and persistence with therapy may be poor. METHODS: This primary care database study assessed persistence with therapy over one year after first prescription of inhaled corticosteroid (ICS) for children aged 2-14 years with a diagnosis of asthma. Children with intermittent asthma were excluded. Discontinuation was defined as no ICS prescription during the last three months of the follow-up year. RESULTS: 2220 of 7375 children receiving a first prescription for ICS had persistent asthma. Mean (±SD) age was 7.3 (±3.8) years; 59.5% were male. A total of 745 (33.6%) continued initial ICS, 133 (6.0%) received add-on therapy, 150 (6.8%) switched to another asthma therapy, and 1192 (53.7%) discontinued therapy. These percentages were similar for children aged 2-5 or 6-14 years. CONCLUSION: Persistence with first-time ICS monotherapy is poor among children with persistent asthma.

Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials.

PURPOSE: The impact of benzodiazepines on the efficacy and safety of esketamine as a rapid-acting antidepressant remains unclear. MATERIALS AND METHODS: Data from two identically designed, randomized double-blind studies were pooled and analyzed on a post-hoc basis. In both studies, adults with major depressive disorder with acute suicidal ideation or behavior were randomized to placebo or esketamine 84 mg nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care (initial hospitalization and newly initiated or optimized oral antidepressant[s]). Efficacy and safety were analyzed in two groups based on whether patients used concomitant benzodiazepines, which were prohibited within 8 hours before and 4 hours after the first dose of esketamine and within 8 hours of the primary efficacy assessment at 24 hours. The primary efficacy endpoint - change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score - was analyzed using ANCOVA. RESULTS: Most patients (309/451, 68.5%) used concomitant benzodiazepines. Greater decrease in MADRS total score was observed with esketamine (mean [SD]: -16.1 [11.73]) versus placebo (-12.6 [10.56]) at 24 hours (least-squares mean difference: -3.7, 95% CI: -5.76, -1.59). The differences between the esketamine and placebo groups were clinically meaningful, irrespective of benzodiazepine use (benzodiazepine: -4.3 [-6.63, -1.89]; no benzodiazepine: -3.1 [-6.62, 0.45]). Among patients taking esketamine, change in MADRS total score was not significantly different between patients taking benzodiazepines (-15.8 [11.27]) versus those not taking benzodiazepines (-16.8 [12.82]) (least-squares mean difference: 1.1, [-2.24, 4.45]). Among esketamine-treated patients, the incidence of sedation was higher with benzodiazepine use, whereas dissociation was similar. CONCLUSION: Benzodiazepines do not meaningfully affect the rapid-acting antidepressant effect of esketamine at 24 hours post-first dose among patients with MDD and acute suicidal ideation or behavior.

A retrospective chart review study to quantify the monthly medical resource use and costs of treating patients with treatment resistant depression in the United Kingdom.

INTRODUCTION: Major depressive disorder (MDD) is a globally prevalent chronic psychiatric illness with a significant disease impact. As many as 30% of patients with MDD do not adequately respond to two therapies and are considered to be treatment resistant. This study aimed to quantify healthcare costs associated with treatment resistant depression (TRD) in the UK. METHODS: A retrospective chart review of patients with TRD was conducted in primary and secondary care settings over a 2 year period. Data abstracted from medical records of patients included demographics, clinical characteristics and healthcare resource utilization (HCRU; number of consultations, use of Crisis Resolution and Home Treatment Teams [CRHTTs], non-drug and drug interventions, and hospitalizations). HCRU per patient per month (28 days) was calculated for three health states: major depressive episode (MDE), remission and recovery. Unit costs were from the British National Formulary (BNF) and the Personal Social Services Research Unit (PSSRU). RESULTS: A total of 295 patients with TRD were recruited between January 2016 and May 2018. The mean age of the total sample was 43.3 years; 60.3% were female. Costs per patient, per 28 days, were highest in the MDE state, with the average cost (£992) mainly driven by consultations, non-drug treatment, hospitalizations and CRHTT, with a considerable fall in costs as patients moved into remission and subsequent recovery. CONCLUSION: The results suggest that antidepressant treatments for TRD that are more effective in reducing the time spent in an MDE health state, and helping patients achieve remission and recovery, are essential for reducing the overall HCRU and costs in patients with TRD. Cost of TRD in the UK Strengths and limitations of this study This observational study of TRD is the first to assess the HCRU impact associated with different predefined health states. Using retrospective data from both primary and secondary care physicians from regions across the UK ensures a representative real-world patient population. One limitation is that the selection of patients is based on criteria that define TRD that rely on physician judgement. Although the study captures direct HCRU costs, the indirect costs of lost productivity and care are not included in the overall burden. This study has defined the current clinical management of patients with TRD in the UK and provides an estimate of the associated HCRU and associated costs.

Pitfalls of Cost-Effectiveness Analysis in Practice: A TRD Case Example in the United States with Esketamine Versus Oral Antidepressants.

DISCLOSURES: The writing of this letter was supported by Janssen Scientific Affairs. The authors are employees of Janssen Scientific Affairs or Janssen Global Services (Johnson & Johnson).

Good hydrolysis activity on raffinose family oligosaccharides by a novel α-galactosidase from Tremella aurantialba.

An α-galactosidase designated as TAG was purified from the dried fruit bodies of Tremella aurantialba with 182.5-fold purification. The purification procedure involved ion exchange chromatography on Q-sepharose, DEAE-Cellulose, and Mono Q and gel filtration by FPLC on Superdex 75. The purified α-galactosidase was a monomeric protein with a molecular mass of 88 kDa. The optimal pH of TAG was 5.0 and more than 60% of the original enzyme activity remained at pH 2.0 and 3.0. Its optimal temperature was 54 °C with good thermo-stability, 30.8% of the original activity was retained after exposure to a temperature of 70 °C for 1 h. The metal ions Hg2+, Cu2+, Fe3+ and Mg2+ strongly inhibited the enzyme activity. The enzyme activity was found to be inhibited by N-bromosuccinimide indicating that tryptophan was essential to the catalytic activity of α-galactosidase. The enzyme completely hydrolysed stachyose and partially hydrolysed raffinose to galactose at 50 °C within 6 h as detected by thin layer chromatography and the dinitrosalicylic acid method and the content of reducing sugar reached 4.36 mg/mL.

A retrospective analysis to estimate the healthcare resource utilization and cost associated with treatment-resistant depression in commercially insured US patients.

OBJECTIVE: The economic burden of commercially insured patients in the United States with treatment-resistant depression and patients with non-treatment-resistant major depressive disorder was compared using data from the Optum Clinformatics™ claims database. METHODS: Patients 18-63 years on antidepressant treatment between 1/1/13 and 9/30/13, who had no treatment claims for depression 6 months before the index date (first antidepressant dispensing), and who had a major depressive disorder or depression diagnosis within 30 days of the index date, were included. Treatment-resistant depression was defined as receiving 3 antidepressant regimens during 1 major depressive disorder episode. Patients with treatment-resistant depression were matched with patients with non-treatment-resistant major depressive disorder at a 1:4 ratio using propensity score matching. The study consisted of 1-year baseline (pre-index) and 2-year follow-up (post index) periods. Cost outcomes were compared using a generalized linear model. RESULTS: 2,370 treatment-resistant depression and 9,289 non-treatment-resistant major depressive disorder patients were included. In year 1 of the follow-up period, compared with non-treatment-resistant major depressive disorder, patients with treatment-resistant depression had: more emergency department visits (odds ratio = 1.39, 95% confidence interval = 1.24-1.56); more inpatient hospitalizations (odds ratio = 1.73, 95% confidence interval = 1.46-2.05); longer hospital stays (mean difference vs non-treatment-resistant major depressive disorder = 2.86, 95% confidence interval = 0.86-4.86 days); and more total healthcare costs (mean difference vs non-treatment-resistant major depressive disorder = US$3,846, 95% confidence interval = $2,855-$4,928). These patterns remained consistent in year 2 of the follow-up period. CONCLUSION: Treatment-resistant depression was associated with higher healthcare resource utilization and costs versus non-treatment-resistant major depressive disorder in this commercially insured cohort of patients in the United States.

Prevalence and risk factors for anaemia in pregnant women: a population-based prospective cohort study in China.

Maternal anaemia is a common pregnancy complication in developing countries; however, its epidemiology remains largely unexplored in China. This study was designed to explore the epidemiology and risk factors of anaemia during pregnancy. A prospective cohort study was conducted, using data from a population-based pregnancy-monitoring system in 13 counties in East China (1993-96). Women who delivered singleton infants at 20-44 weeks with at least one haemoglobin assessment during pregnancy were included (n = 164 667). The prevalence of anaemia (haemoglobin < 10 g/dL) during pregnancy as well as in each trimester was estimated. Multivariable log-binomial regression models were used to evaluate risk factors. The overall prevalence of anaemia in pregnancy was 32.6%, with substantial variations across trimesters (11.2%, 20.1% and 26.2% in the 1st, 2nd and 3rd trimesters respectively). Risk factors for anaemia included older maternal age, education below junior high school (prevalence rate ratio [RR] 1.10, 95% confidence interval [CI] 1.08, 1.12), farming occupation (1.05, 95% CI 1.03, 1.06), and mild pregnancy-induced hypertension (PIH) (RR 1.09, 95% CI 1.05, 1.13) and severe PIH (RR 1.13, 95% CI 1.06, 1.19). Peri-conception folic acid use was associated with a reduced risk for anaemia in the 1st trimester (RR 0.75, 95% CI 0.72, 0.78). Initiating prenatal care after the 1st trimester was associated with increased risk of anaemia in the 2nd and 3rd trimesters. Our study found anaemia during pregnancy is highly prevalent in this indigenous Chinese population. The risk increases with the severity of hypertensive disorders. Folic acid supplementation during the peri-conception period is associated with reduced risk of 1st trimester anaemia.

Rates of asthma attacks in patients with previously inadequately controlled mild asthma treated in clinical practice with combination drug therapy: an exploratory post-hoc analysis.

BACKGROUND: Differences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON). METHODS: This was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination with a LABA, started concomitant MON treatment as part of their routine care. Rates of asthma- and allergic rhinitis-related medical resource use in the 12-months after the initial (index) MON prescription were compared in the ICS/MON and ICS/LABA/MON groups. An asthma attack was defined as an asthma-related hospitalization, ER visit, or use of an oral corticosteroid. RESULTS: Of the total of 344 patients, 181 (53%) received ICS/MON and 163 (47%) received ICS/LABA/MON in the post-index period for means of 10.5 and 11.4 months, respectively, (P < 0.05). Short-acting beta-agonists were used by 74.6% in the ICS/MON and 71.8% in the ICS/LABA/MON groups (P > 0.05). An asthma attack occurred in 4.4% of the ICS/MON group and 6.8% of the ICS/LABA/MON group (P > 0.05). The adjusted odds of an asthma attack in the post-index period in the ICS/LABA/MON group relative to the ICS/MON group was 1.24, 95% confidence interval 0.35-4.44. CONCLUSION: In this observational study of combination drug treatment of mild persistent asthma and allergic rhinitis, no difference was observed between LABA/ICS/MON combination therapy and the ICS/MON combination without LABA use, for the rate of asthma attacks over one year.

Utilization of parenteral anticoagulants and warfarin: impact on the risk of venous thromboembolism recurrence in the outpatient setting.

BACKGROUND: Clinical guidelines recommend parenteral anticoagulation therapy with an early initiation of warfarin therapy for the treatment of patients with acute venous thromboembolism (VTE) and the prevention of recurrence. OBJECTIVES: To evaluate the outpatient utilization of parenteral anticoagulant therapy and warfarin among patients with VTE, and to examine the effects of parenteral anticoagulant use and the time to warfarin initiation from VTE diagnosis on the risk for VTE recurrence. METHODS: The Truven Health MarketScan Commercial Claims Database was used to identify patients aged 18 to 64 years who had an outpatient claim for deep-vein thrombosis or pulmonary embolism between January 2010 and December 2011 (ie, index date) and had no VTE diagnosis or treatment during the 12 months before the index date, had no hospital or emergency department VTE claim within 7 days after the index outpatient VTE claim, and had received warfarin <30 days after the index date. A recurrent VTE event was defined as a VTE-related emergency department visit or hospitalization within 8 to 365 days after the index date. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) associated with VTE recurrence risk related to parenteral anticoagulant use and warfarin initiation timing. RESULTS: A total of 5820 patients were included in the study (mean age, 50.5 years); of these, 45% were female. A total of 75.7% (4403) of the patients receiving warfarin also received a parenteral anticoagulant, and the median time from VTE diagnosis to warfarin initiation was 5 days for parenteral anticoagulant users compared with 11 days for nonusers. Parenteral anticoagulant use was associated with a 49% recurrent VTE risk reduction (HR, 0.51; 95% confidence interval [CI], 0.43-0.60; P <.001). Each day of delayed warfarin initiation from the diagnosis of acute VTE was associated with a 1% increase in the risk for VTE recurrence (HR, 1.01; 95% CI, 1.01-1.02; P = .003). CONCLUSIONS: Overall, 1 in 4 patients with VTE who had received warfarin in the outpatient setting did not receive parenteral anticoagulation therapy. Among those who received warfarin, its initiation was not always timely, despite its positive effects on reducing VTE recurrence. These findings highlight the potential quality-of-care concerns associated with the failure to use or the delayed implementation of guideline-recommended VTE treatment, and the need to improve compliance with clinical guidelines in the treatment of patients with VTE.