Comparative analysis of length of stay,hospitalization costs,opioid use,and discharge status among spine surgery patients with postoperative pain management including intravenous versus oral acetaminophen

Background: Recovery from spine surgery is oriented toward restoring functional health outcomes while reducing resource use. Optimal pain management is a key to reaching these objectives. We compared outcomes of spine surgery patients who received standard pain management including intravenous (IV) acetaminophen (APAP) vs. oral APAP.

Methods: We performed a retrospective analysis of the Premier database (January 2012 to September 2015) comparing spine surgery patients who received pain management with IV APAP to those who received oral APAP, with no exclusions based on additional pain management. We performed multivariable logistic regression for the discharge and all cause 30-day readmission to the same hospital outcomes and instrumental variable regressions using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED) outcomes. Models adjusted for age, gender, race, admission type, 3M All Patient Refined Diagnosis Related Group severity of illness and risk of mortality, hospital size, and indicators for whether the hospital was an academic center and whether it was urban or rural.

Results: We identified 112,586 spine surgery patients with 51,835 (46%) having received IV APAP. Subjects averaged 57 and 59 years of age respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians and female. In our adjusted models, IV APAP was associated with 0.68 days shorter LOS (95% CI: ?0.76 to ?0.59, p?p?p?p?Conclusions: Compared to oral APAP, managing post-spine-surgery pain with IV APAP is associated with less resource use, lower costs, lower doses of opioids, and improved discharge status.     

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial

ABSTRACT

Objective: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany.

Research design and methods: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n?=?368), or levofloxacin and ceftriaxone (n?=?365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5–7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective.

Results: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was €2190 for the moxifloxacin group, and €2619 for the levofloxacin + ceftriaxone group (difference –€430, 95% CI: –€138, –€740; p?<?0.05). Variability in total costs was wide, with some patients accruing up to €18?000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (–€470, 95% CI: –€522, –€421), and accounted for between 15 and 30% of total costs.

Conclusions: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.     

Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind,randomized, placebo- and oxycodone controlled release-controlled studies

Objective: To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain.

Methods: Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).

Results: A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of –0.41 [95% CI?=?–0.65, –0.16; p?=?0.001] at week 12 and –0.35 [95% CI?=?–0.58, –0.12; p?=?0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p?p?Conclusions: The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.     

The Clinical Management of Acetaminophen Poisoning in a Community Hospital System: Factors Associated with Hospital Length of Stay

Acetaminophen (APAP) overdose is the most common pharmaceutical poisoning. The objective of this study was to examine the management of patients admitted for treatment of APAP overdose. Factors impacting hospital length of stay (LOS) were of particular interest. This was a retrospective cohort study of patients admitted to Kaiser Permanente Northern California hospitals for APAP overdose from July 2003 through December 2007. Medical records were abstracted for patient demographic data, key factors of overdose, California Poison Control System (CPCS) contact, data regarding hospital course, transfer for liver transplantation, and death. Four hundred thirty-five patients were included. The mean hospital LOS was 66.5 h (95% CI 62.1, 71.0). Four patients (0.9%) died. Eight patients (1.8%) were transferred for liver transplantation, but all of these patients later recovered without transplant. Of 289 cases eligible for placement on the Rumack–Matthew nomogram (acute ingestion with known time of ingestion <24 h and normal liver enzymes), 161 (55.7%) had APAP levels above the “200” line and 77 (26.6%) fell below the “150” line. CPCS was contacted in 295 cases (67.8%). Mean LOS in cases with CPCS consultation was 61.9 h (95% CI 57.2, 66.5 h) versus 76.3 h (95% CI 66.6, 86.0 h) in those without. LOS in cases treated with IV NAC was 67.1 h (95% CI 57.7, 76.5 h) versus 66.4 h (95% CI 61.2, 71.5 h) in cases treated with oral NAC. Many patients admitted for APAP overdose had serum APAP levels below the minimum toxicity level. Use of IV NAC did not impact hospital LOS. CPCS consultation appeared to decrease mean hospital LOS.     

Tapentadol prolonged-release for moderate-to-severe chronic osteoarthritis knee pain: a double-blind,randomized, placebo- and oxycodone controlled release-controlled study

Objective: To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain.

Methods: Patients (n?=?990) were randomized (1:1:1) to tapentadol PR, oxycodone controlled release (CR; reference compound for assay sensitivity), or placebo for a double-blind 3-week titration and 12-week maintenance period. Primary efficacy end-points were change from baseline in average pain intensity at week 12 of maintenance (US end-point) and over the entire maintenance period (non-US end-point) with “last observation carried forward” as imputation method for missing scores.

Results: Both primary end-points were not significantly different for tapentadol PR nor for oxycodone CR vs placebo at week 12 (least squares [LS] mean difference?=?–0.3 [95% CI?=?–0.61–0.09]; p?=?0.152 and 0.2 [95% CI?=?–0.16–0.54]; p?=?0.279, respectively) and over the maintenance period (LS mean difference?=?–0.2 [95% CI?=?–0.55–0.07]; p?=?0.135 and 0.1 [95% CI?=?–0.18–0.44]; p?=?0.421, respectively). Considerably more patients receiving tapentadol PR than oxycodone CR completed the trial (58.3% vs 36.6%). This is consistent with better results with tapentadol PR on the overall health status (PGIC) compared to oxycodone CR. Indeed, respectively, 56% and 42.5% rated at least “much improved” at the end of treatment. Incidences of gastrointestinal adverse events were higher for both active treatments compared to placebo. Tapentadol PR was associated with a better gastrointestinal tolerability profile with incidences of constipation (17.9% vs 35%) and of the composite of nausea and/or vomiting (23.8% vs 46.8%) significantly lower vs oxycodone CR (p?Conclusions: The study did not demonstrate assay sensitivity. The finding that both primary end-points for tapentadol PR were not met can, thus, not be interpreted. Tapentadol PR was better tolerated than oxycodone CR, largely due to fewer gastrointestinal side-effects.     

A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery

ABSTRACT

Objective: To assess clinical efficacy of IV paracetamol 1?g and IV metamizol 1?g on a 24‐h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I–III patients undergoing retinal surgery.

Research design and methods: General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1?g/100?mL (Para Group), of metamizol 1?g/100?mL (Meta Group), or of 100?mL of saline solution as placebo control (Plac Group) 30?min before arrival in the recovery area and every 6?h up to 24?h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication.

Main outcome measures: The primary efficacy variables were pain scores at rest over 30?h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement.

Results: Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (?p = 0.03). For the time effects a significant result was detected (?p < 0.001). The main effect between the three treatment groups was significantly different (?p = 0.01). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (?p = 0.024; mean difference 14.8; 95% CI 1.6–28.0), between the Plac Group and the Meta Group in favour of IV metamizol (?p = 0.025; mean difference 14.4; 95% CI 1.5–27.4), and no significant difference between the Para Group and the Meta Group (?p = 1.0; mean difference 0.4; 95% CI –12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (?p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (?p = 0.032; mean difference 17.9; 95% CI 1.3–34.6), a difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (?p = 0.081; mean difference 15.0; 95% CI –1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (?p = 1.0; mean difference 2.9; 95% CI –13.8 6 to 19.6).

None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (?p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (?p = 0.07). There was no difference in sedation between the Meta and the Para Groups (?p = 0.84).

Conclusion: IV paracetamol 1?g has a similar analgesic potency as IV metamizol 1?g for postoperative analgesia after retinal surgery.     

Safety,effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population

Abstract

Objective: To compare safety, effectiveness, and healthcare costs of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, recurrent venous thromboembolism (VTE), and all-cause hospitalization among elderly Medicare VTE patients prescribed warfarin vs apixaban.

Methods: Using 100% Medicare data, elderly patients prescribed apixaban or warfarin within 30 days after a VTE encounter were identified. Patients had continuous health plan enrollment and no parenteral or oral anticoagulant use ≤6 months preceding the VTE encounter. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazard models were used to assess the risk of MB, CRNM bleeding, recurrent VTE, and all-cause hospitalization. Generalized linear and two-part models were used to estimate MB-, recurrent VTE-, and all-cause related costs (per patient per month [PPPM]).

Results: In the pre-matched cohort, 25,284 (66.9%) patients were prescribed warfarin and 12,515 (33.1%) apixaban. After 1:1 PSM, 11,363 matched pairs of apixaban-warfarin patients were included for a mean follow-up of 4.0 and 4.4 months, respectively. Matched cohorts had a mean age of 78 years and mean Charlson Comorbidity Index score of 2.9. Warfarin was associated with a higher risk of MB (hazard ratio [HR]?=?1.31; 95% confidence interval [CI]?=?1.10–1.57) and CRNM bleeding (HR?=?1.31; 95% CI?=?1.19–1.43) vs apixaban. The risks of recurrent VTE (HR?=?0.96; 95% CI?=?0.70–1.33) and all-cause hospitalization (HR?=?1.05; 95% CI?=?0.99–1.12) were similar among warfarin and apixaban patients. Warfarin patients had higher MB-related ($147 vs $75; p?=?.003) and all-cause costs PPPM ($3,267 vs $3,033; p?<?.001), but similar recurrent VTE-related medical costs PPPM ($30 vs $36; p?=?.516) vs apixaban patients.

Conclusions: Warfarin was associated with significantly higher risk of MB and CRNM bleeding as well as higher MB-related and all-cause costs vs apixaban patients. Recurrent VTE risk and costs were similar among warfarin and apixaban patients.     

Etomidate versus propofol sedation for electrical external cardioversion: a meta-analysis

Objective: To compare the efficacy and safety of etomidate vs propofol sedation for electrical cardioversion.

Methods: The authors searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, Google Scholar, Koreamed, and KMBASE databases to identify all randomized controlled trials that compared etomidate and propofol sedation for cardioversion in adult patients. Induction and recovery time, success rate, number of shocks, and cumulative energy were evaluated. Adverse effects, including respiratory and cardiovascular complications, myoclonus, and nausea and vomiting, were also assessed.

Results: A total of nine studies, involving a total of 430 patients, were included. Induction and recovery time, success rate, number of shocks, and cumulative energy were similar. The incidences of hypotension and respiratory depression were significantly higher in the propofol group than in the etomidate group (risk ratio [RR]?=?0.11, 95% confidence interval (CI)?=?0.02–0.74, I²?=?0%; RR?=?0.50, 95% CI?=?0.32–0.77, I²?=?47%, respectively). The incidences of myoclonus and nausea or vomiting were significantly higher in the etomidate group than in the propofol group (RR?=?8.89, 95% CI = 4.59–17.23, I²?=?9%; RR?=?5.13, 95% CI?=?1.72–15.31, I²?=?31%, respectively).

Conclusions: Issues affecting efficacy, including induction and recovery time, success rate, number of shocks, and cumulative energy, were comparable between etomidate and propofol sedation. Regarding safety issues, propofol sedation resulted in hypotension and respiratory depression more frequently; however, initiation of positive pressure ventilation was comparable. Etomidate sedation caused myoclonus and nausea or vomiting more frequently.     

The correlation between metastasis-free survival and overall survival in non-metastatic castration resistant prostate cancer patients from the Medical Data Vision claims database in Japan

Background and purpose: Several recent randomized controlled trials (RCTs) in non-metastatic castration resistant prostate cancer (nmCRPC) have demonstrated a significant improvement in metastasis-free survival (MFS); however, an improvement in overall survival (OS) is not reported yet. Since the surrogacy of MFS to OS has not been formally investigated in nmCRPC in Japan, this study evaluated the correlation between MFS and OS among a nmCRPC population in Japan.

Methods: This is a retrospective longitudinal observational cohort study in patients with nmCRPC using the Japanese Medical Data Vision (MDV) database covering over 20 million patients. A total of 1236 patients with CRPC who had no prior medical history of cancer except prostate cancer and no distant metastasis, and who fulfilled PCWG2 criteria, were identified. Following the identification of nmCRPC, patients’ medical records were investigated for subsequent events of metastasis and death.

Results: The median follow-up time was 24?months. Median MFS was 28?months (95% CI: 24.0 to 33.0?months) and median OS could not be estimated (95% CI: not estimated). There was a statistically significant correlation between MFS and OS (Pearson’s correlation coefficient?=?0.62; 95% CI: 0.58–0.65; p?<?.0001, Spearman’s correlation coefficient?=?0.62; 95% CI: 0.58–0.65; p?<?.0001 and Kendall’s τ statistic?=?0.53; 95% CI: 0.49–0.56; p?<?.0001).

Conclusions: The results of this study indicate a significant correlation between MFS and OS. It may justify the usefulness of MFS as surrogate for OS in nmCRPC.     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

High one-year mortality following hospitalization for severe hypoglycemia among patients with diabetes mellitus: findings of a retrospective cohort study at an acute tertiary care hospital in Singapore

Objectives: Little is known about the 1-year short-term mortality rate following hospital admissions with severe hypoglycemia. This study aimed to determine the factors associated with increased 1-year mortality rate following hospitalization in diabetes patients admitted with severe hypoglycemia to the Singapore General Hospital.

Methods: Clinical, biochemical, and 1-year mortality data from diabetes patients who were admitted with severe hypoglycemia in the year 2014 were extracted from institutional medical records. Patients who passed away during the episode of admissions with severe hypoglycemia were excluded from the analysis. The clinical and biochemical factors between patients who survived and those who did not survive within 1 year following admission were compared using logistic regression analysis.

Results: Three hundred and four patients (181 female and 123 male) were admitted with severe hypoglycemia in 2014, and the mean capillary blood glucose on admission was 2.3?±?0.7?mmol/L. Sixty-three (20.7%) patients died within 1-year post-discharge from the hospital. Compared with patients who survived 1-year post-discharge from the hospital, non-survivors were older (69.3?±?11.0 vs 75.5?±?11.2 years, p?<?.001), had longer lengths of stay (LOS) (5.0?±?7.4 vs 9.0?±?12.8 days, p?=?.02), and had a higher Charlson Comorbidity Index (CCI) (4.1?±?1.9 vs 5.9?±?2.4, p?<?.001). Factors associated with increased 1-year mortality risk were age (odds ratio [OR]?=?1.06; 95% confidence interval [CI]?=?1.03–1.09, p?<?.01), LOS in hospital (OR?=?1.01; 95% CI?=?1.01–1.08, p?<?.01), and CCI (OR?=?1.51; 95% CI?=?1.31–1.75, p?<?.01), respectively.

Conclusions: Older diabetes patients with more comorbidities and longer LOS were at increased risk of dying within a year of discharge after hospitalization with severe hypoglycemia. Admission with severe hypoglycemia has important prognostic implications. Healthcare professionals should address hypoglycemia and other health issues during the hospital admissions.     

Healthcare costs among adults with type 2 diabetes initiating saxagliptin or linagliptin: a US-based claims analysis

Objective: To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class.

Methods: Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period. Saxagliptin and linagliptin initiators were matched using propensity score methods. Cost ratios (CRs) and predicted costs were estimated from generalized linear models and recycled predictions.

Results: There were 34,560 saxagliptin initiators and 18,175 linagliptin initiators identified (mean ages 57 and 59; 55% and 56% male, respectively). Before matching, saxagliptin initiators had significantly lower all-cause total healthcare costs than linagliptin initiators (mean?=?$15,335 [SD $28,923] vs. mean =?$20,069 [SD $48,541], p?p?n?=?16,069 per cohort), saxagliptin initiators had lower all-cause follow-up costs than linagliptin initiators (CR?=?0.953, 95% CI?=?0.932–0.974, p?p?=?0.017; predicted costs?=?$3989 vs. $4159).

Conclusions: Adult patients with T2D initiating treatment with saxagliptin had lower total all-cause healthcare costs and diabetes-related medical costs over 1 year compared with patients initiating treatment with linagliptin.     

Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

Impact of postoperative nausea and vomiting prophylaxis with dexamethasone on the risk of recurrence of endometrial cancer

Objective:

To assess whether antiemetic doses of dexamethasone are associated with an increased risk of cancer recurrence in women who underwent surgery for endometrial cancer.

Research design and methods:

This is a retrospective study at an academic university medical center. Women who underwent surgery for endometrial cancer from 2003 to 2007 were identified from a prospectively collected endometrial cancer database. Perioperative records were reviewed to determine administration of dexamethasone. Patients were divided into two groups: those who received dexamethasone 4–10?mg for postoperative nausea and vomiting prophylaxis and those who did not receive dexamethasone. We collected information on patient demographics, cancer stage, cancer grade, histology, year of surgery, chemotherapy, radiation therapy, duration of surgery, perioperative blood transfusion, receipt of epidural analgesia, dose of dexamethasone given, follow-up time, and co-morbidities.

Main outcome measures:

Primary endpoint was recurrence-free survival. Secondary endpoints included progression-free survival and overall survival.

Results:

Three hundred and nine patients were included in the analysis. There were no significant differences between dexamethasone exposed (n?=?107) and non-exposed patients in recurrence-free survival ([5 year estimate (95% CI)]?=?71 (62–82) % vs. 71 (64–78) %, p?=?1.0), progression-free survival (57 [47–68] % vs. 60 [53–68] %, p?=?0.9), or overall survival (68 [59–79] % vs. 71 [64–79] %, p?=?1.0). In univariate analysis, significant predictors of recurrence-free survival were tumor stage (p?=?0.02), tumor grade (0.003) and receipt of adjuvant chemotherapy (p?<?0.001). In the multivariable model, higher tumor grade (hazard ratio [HR] [95% CI]?=?2.3 [1.4–3.9], p?=?0.002) and receipt of adjuvant chemotherapy (3.2 [1.8–5.8], p?<?0.001), but not dexamethasone (0.9 [0.5–1.5], p?=?0.7), were significant predictors of recurrence-free survival.

Conclusions:

Dexamethasone administration was not associated with an increased risk of recurrence in women having surgery for endometrial cancer. Limitations of the study include its retrospective single center design and the fact that administration of dexamethasone was not randomized.     

Comparison of Medicaid spending in schizoaffective patients treated with once monthly paliperidone palmitate or oral atypical antipsychotics

Background Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients.

Objective To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients.

Methods Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009–December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA.

Results A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD]?=?-$383, p?<?0.001; IPTW: MMCD?=?-$403, p?=?0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD?=?$270, p?<?0.001; IPTW: MMCD?=?$350, p?<?0.001) and resulted in similar total healthcare cost (PSM: MMCD?=?-$113, p?=?0.414; IPTW: MMCD?=?-$53, p?=?0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR]?=?0.85, p?=?0.128; IPTW: IRR?=?0.96, p?=?0.004) and fewer hospitalization days (PSM: IRR?=?0.74, p?=?0.008; IPTW: IRR?=?0.85, p?<?0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio?=?0.89, p?=?0.041).

Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs (potentially over-estimated). Also changes in treatment over time were possible.

Conclusions Total healthcare costs associated with the use of once monthly PP versus OAAs appeared comparable; higher pharmacy costs for PP users were offset by lower medical costs related to fewer and shorter inpatients visits.     

Transitioning from oral risperidone or paliperidone to once-monthly paliperidone palmitate: a real-world analysis among Veterans Health Administration patients with schizophrenia who have had at least one prior hospitalization

Abstract

Objective: To address gaps in the literature on healthcare resource utilization (HRU) and costs among patients with schizophrenia and prior hospitalization who transition from oral risperidone or paliperidone (oral ris/pali) to once-monthly paliperidone palmitate (PP1M) in a real-world setting by comparing treatment patterns, HRU, and costs 12-months pre- and post-transition to PP1M among Veterans Health Administration (VHA) patients affected by schizophrenia who have had ≥1 hospitalization.

Methods: VHA patients with schizophrenia (aged ≥18?years) who initiated oral ris/pali, had ≥1 all-cause inpatient stay, and transitioned to PP1M from January 2015–March 2017 were included from the VHA database. The first transition date to PP1M was identified as the index date. Patients were required to have continuous health plan eligibility for 12?months pre- and post-PP1M. Outcomes were compared using the Wilcoxon signed-rank and McNemar’s test, as appropriate.

Results: The study included 319 patients (mean [SD] age?=?51.6 [4.2] years) during 12 months of baseline and follow-up. During pre-PP1M transition, 7.2% of the patients were adherent (proportion of days covered [PDC]?≥?80%) to oral ris/pali. Post-PP1M transition, 27.6% of the patients were adherent to PP1M. Comparison of HRU outcomes from the pre- to post-PP1M transition revealed significantly lower all-cause inpatient stays (3.5 vs 1.4, p?<?.0001) and shorter inpatient length of stay (43.4 vs 18.3?days, p?<?.0001). Similar trends were seen for mental health and schizophrenia-related HRU. Cost outcome comparison indicated significantly lower all-cause inpatient costs ($64,702 vs $24,147, p?<?.0001), total medical costs ($87,917 vs $56,947, p?<?.0001), and total costs ($91,181 vs $69,106, p?<?.0001). A similar trend was observed for mental health and schizophrenia-related costs.

Conclusions: Transitioning from oral ris/pali to PP1M may significantly improve HRU and provide potential cost savings in VHA patients with schizophrenia and ≥1 prior hospitalization.     

Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data

Objective: Early initiation of antipsychotic treatment in schizophrenia is associated with improved outcomes. This study aimed to determine if initiation of long-acting injectable (LAI) antipsychotic treatment early in a new schizophrenia episode is associated with lower hospitalization rates and healthcare costs in a real-world setting.

Methods: This retrospective (January 1, 2007–June 30, 2016) cohort analysis used claims from Truven Health Analytics MarketScan Commercial, Medicaid, and Medicare Supplemental databases. In adults ≥18?years with a new episode of schizophrenia, two mutually exclusive cohorts were identified based on time from first recorded schizophrenia diagnosis date to first date of LAI initiation (index date): ≤1?year (early initiators) and >1?year (late initiators). Logistic and general linear regression models were performed to estimate adjusted hospitalization rate and healthcare costs in a 1-year follow-up, controlling patient demographic and clinical characteristics, insurance type, baseline all-cause hospitalizations and ED visits, and baseline psychiatric medication use.

Results: Of the subjects, 32% (n?=?1388) initiated treatment early and 68% (n?=?2978) initiated treatment later. In risk-adjusted models, all-cause hospitalization rates were 22.2% (95% CI?=?19.9–24.6%) in early initiators and 26.9% (95% CI?=?25.2–28.7%) in late initiators (p?=?.002). Of early initiators, 14.1% (95% CI?=?12.3–16.1%) had a psychiatric hospitalization vs 19.2% (95% CI?=?17.7–20.8%) of late initiators (p?<?.001). Adjusted psychiatric healthcare costs were significantly lower in early initiators compared with late initiators [mean (95% CI)?=?$21,545 (20,355–22,734) vs $24,132 (23,330–24,933)] (p?<?.001).

Conclusions: LAI initiation within 1 year of a new schizophrenia episode led to lower hospitalization rates and healthcare costs compared with LAI initiation more than 1 year after a new episode.     

Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized,double-blind,clinical trials

SUMMARY

Aims: To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials.

Patients and methods: Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800?mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500?mg twice daily for 10?days. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31–36). Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related.

Results: Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% [428/482] vs 90.1% [272/302] – difference: –1.3%; 95% CI: –6.0, 3.4), telithromycin treatment for 5, 7, or 10?days was associated with significantly fewer CAP-related hospitalizations (?p = 0.023) and CAP-related hospital days (?p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients). Accordingly, estimated CAP-related hospitalization costs were significantly lower (?p = 0.025) for telithromycin recipients (US$30?231 less per 100 patients). CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin – the approved dosing regimen for CAP – were significantly lower (?p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin.

Conclusions: Data from this study indicate that telithromycin 800?mg once daily for 5, 7, or 10?days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500?mg twice daily for 10?days. Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.     

Characteristics of children and adolescents first prescribed proton pump inhibitors or histamine-2-receptor antagonists: an observational cohort study

Objective: To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H₂RAs).

Methods: Observational studies were conducted using The Health Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0–18 years who were first prescribed a PPI or H₂RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H₂RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex.

Results: The mean age (years) was higher in the PPI than in the H₂RA cohorts (THIN 12.3 [n?=?8204] vs 5.4 [n?=?7937], PHARMO 11.0 [n?=?15 362] vs 7.1 [n?=?6168]). Previous respiratory disease was more common in the PPI than in the H₂RA cohort in THIN (OR?=?1.19, 95% CI?=?1.08–1.30), as were asthma and respiratory medication use in PHARMO (OR?=?1.27, 95% CI?=?1.12–1.45 and OR?=?1.23, 95% CI?=?1.10–1.38, respectively) and oral corticosteroid use in both databases (OR?=?1.45, 95% CI?=?1.10–1.92 [THIN]; OR?=?2.80, 95% CI?=?2.11–3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H₂RA cohorts in both databases.

Conclusions: Pediatric patients receiving PPIs and those receiving H₂RAs may represent different patient populations. PPIs may be more commonly prescribed than H₂RAs among patients with respiratory diseases.     

The effect of antibiotic prophylaxis for acute pelvic inflammatory disease after hysterosalpingography: a retrospective cohort study

Aims: Concerns about acute pelvic inflammatory disease (PID) after hysterosalpingography (HSG) have been raised since 1980. However, the effectiveness of prophylactic antibiotics remains unclear. This study investigated the effect of antibiotic prophylaxis in women undergoing HSG.

Methods: Women undergoing HSG between 2000 and 2012 were screened from the Taiwan National Health Insurance Research Database for eligibility. The prophylactic cohort included patients using any antibiotics of 1st-generation cephalosporins, doxycycline, clindamycin, and metronidazole, within 7 days before HSG (n?=?3257). Patients not using any antibiotics were registered as the non-prophylactic cohort (n?=?4662). An unconditional logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute PID after HSG associated with prophylactic antibiotics.

Results: The cumulative incidences of acute PID after HSG were 0.46% and 1.42% in the prophylactic and non-prophylactic cohorts, respectively. Prophylactic patients had a significantly reduced estimated relative risk of acute PID compared with non-prophylactic patients (adjusted OR?=?0.33, 95% CI?=?0.19–0.58; p?=?.001). Doxycycline users had the lowest adjusted OR of 0.20 (95% CI?=?0.04–0.81; p?=?.02), followed by users of 1st-generation cephalosporins (adjusted OR?=?0.35, 95% CI?=?0.18–0.68; p?=?.002). Multivariate sub-group analysis verified this protective effect for almost all sub-groups of prophylactic patients.

Conclusions: Antibiotic prophylaxis is associated with a decreased estimated relative risk of acute PID in HSG patients. Doxycycline and 1st-generation cephalosporins may be effective prophylactic regimens for HSG.