Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. METHODS: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. RESULTS: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. CONCLUSIONS: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.

Small bowel lymphangiectasia and angiodysplasia: a positive association; novel clinical marker or shared pathophysiology?

INTRODUCTION: Small bowel angiodysplasia accounts for 30 to 40% of cases of obscure gastrointestinal bleeding and is associated with significant morbidity and mortality. Identifying lesions can be difficult. Small bowel capsule endoscopy (SBCE) is a significant advance on earlier diagnostic techniques. The cause of angiodysplasia is unknown and the natural history poorly understood. Many lesions are thought to arise from a degenerative process associated with ageing, local vascular anomalies, and tissue hypoxia. Nonpathologic lymphangiectasias are commonly seen throughout the small bowel and are considered a normal finding. AIMS: To determine whether there is an association between lymphangiectasias, angiodysplasia, and atherosclerosis related conditions. METHODS: Relevant information was collected from a dedicated SBCE database. Logistic regression analysis was used to examine associations between angiodysplasia, lymphangiectasia, patient demographics, and comorbidity. RESULTS: In all, 180 patients underwent SBCE during the study period, 46 (25%) had angiodysplasia and 47 (26%) lymphangiectasia. Lymphangiectasia were seen in 24 (52%) of 46 with angiodysplasia, in 16 (19%) of 84 with obscure gastrointestinal bleeding without angiodysplasia and in 7 (14%) of 50 without gastrointestinal bleeding. Logistic regression analysis confirmed a strong positive association between angiodysplasia and lymphangiectasia; odds ratio 4.42, P<0.003. Angiodysplasias were also associated with increasing age; odds ratio 1.1. There was no correlation with any other patient characteristic. CONCLUSIONS: Lymphangiectasia are strongly associated with the presence of small intestinal angiodysplasia and may represent a useful clinical marker for this condition. Angiodysplasia are also associated with increasing age. Conditions associated with systemic atherosclerosis did not increase the risk of angiodysplasia.

GERD-related health care utilization, therapy, and reasons for transfer of GERD patients between primary care providers and gastroenterologists in a US managed care setting.

PURPOSE: Patient flow between primary care physicians and gastroenterologists in the continuum of gastroesophageal reflux disease (GERD) care is poorly understood. Using administrative claims data from a large US health plan linked with data abstracted from medical records, we examined: health care resource utilization for GERD subjects treated by primary care physicians (PCPs) and gastroenterologists (GEs), determinants of GERD subject transfer between these physician types, and reasons for GERD therapy change. RESULTS: Within a sample of 169,884 patients, 211,043 PCP-based episodes of care and 40,304 GE-based episodes of care were developed. In unadjusted comparisons, GE episodes were characterized by more endoscopic procedures, on average (50.5/100 episodes), compared with PCP episodes (6.3/100, P < 0.001). Multivariate analysis showed that patients with esophagitis had 57.3% higher odds (P < 0.01) of transfer from PCP to GE compared with patients without esophagitis; patients with esophageal stricture had 98.6% higher odds (P < 0.01) of PCP-GE transfer. Patients with endoscopy during a first GE episode had 32.2% higher odds of transfer to a PCP (P < 0.01). The principal reasons for change in GERD therapy were no change or worsening of symptoms (51.7% of PCP charts; 9.5% of GE charts) and lack of response to therapy (51.7% of PCP charts, 26.2% of GE charts). CONCLUSION: Resource utilization varies greatly based on the physician's specialty. We infer that timely transfer of GERD patients to gastroenterologists when empiric treatment is insufficient may lead to more efficient clinical management.

Negative capsule endoscopy in patients with obscure GI bleeding predicts low rebleeding rates.

BACKGROUND: Wireless capsule endoscopy (CE) is the investigation of choice in obscure GI bleeding (OGIB), with a high diagnostic yield when compared with other modalities. It enables specific treatment to be instigated in a significant proportion of cases, with the aim of reducing rebleeding rates. Little evidence is currently available on the clinical value of a negative study. OBJECTIVE: To determine the long-term (>1 year) outcome in patients who underwent CE to investigate OGIB. METHODS: Consecutive patients with OGIB referred for CE to a single center over an 18-month period were identified. Follow-up data were obtained by reviewing case notes and an internal CE database. Rates of rebleeding were established, and factors associated with rebleeding were assessed by means of univariate and multivariate analysis. RESULTS: Forty-nine patients underwent CE for investigation of OGIB (obscure overt in 25 patients [51%]) between April 2005 and October 2006. Long-term data were available for 42 patients (86%), with a mean (+/- SD) follow-up of 17.3 +/- 6.2 months. Significant (P2) lesions were identified in 24 patients (57%). The overall rebleeding rate was 28%. There was a statistically significant difference in rebleeding between patients with a positive and patients with a negative study, 42% versus 11%, respectively, P < .01. Anticoagulant use was also associated with an increased risk of rebleeding. CONCLUSION: A negative CE study in patients with OGIB is associated with a low rate of recurrent bleeding in the long term (11%). It is reasonable to take an expectant approach with these patients, thus avoiding the need for unnecessary additional investigations.

Burden of multiple sclerosis on direct, indirect costs and quality of life: National US estimates.

BACKGROUND: MS imposes a significant burden on patients, caregivers, employers, and the healthcare system. OBJECTIVE: To comprehensively evaluate the US MS burden using nationally representative data from the Medical Expenditure Panel Survey. METHODS: We identified non-institutionalized patients aged ≥18 with MS (ICD-9 code 340) from 1998 to 2009 and compared them to individuals without an MS diagnosis (non-MS) during the interview year. The cohorts were compared using multivariate regression on direct costs, indirect costs (measured in terms of employment status, annual wages, and workdays missed), and health-related quality of life (HRQoL; measured using Short Form 12, SF-6 Dimensions, and quality-adjusted life years [QALYs]). RESULTS: MS prevalence was 572,312 (95% CI: 397,004, 747,619). Annual direct costs were $24,327 higher for the MS population (n=526) vs. the non-MS population (n=270,345) (95% CI: $22,320, $26,333). MS patients had an adjusted 3.3-fold (95% CI: 2.4, 4.5) increase in the odds of not being employed vs. non-MS individuals and a 4.4-fold higher adjusted number of days in bed (95% CI 2.97, 6.45). On average, MS patients lost 10.04 QALYs vs. non-MS cohort. CONCLUSIONS: MS was associated with higher healthcare costs across all components, reduced productivity due to unemployment and days spent in bed, and lower HRQoL.

Outcomes associated with initiation of tiotropium or fluticasone/salmeterol in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Adherence to long-acting bronchodilator therapy for management of chronic obstructive pulmonary disease (COPD) is a critical clinical and cost issue. Low adherence is associated with relatively higher exacerbation rates and illness burden. PURPOSE: To compare adherence between patients with COPD initiating therapy on tiotropium or fluticasone/salmeterol and examine the association between adherence and respiratory-related costs. PATIENTS AND METHODS: This retrospective claims data analysis evaluated patients initiating tiotropium or combination fluticasone/salmeterol from December 1, 2004 to December 31, 2005. Patients had ≥1 COPD diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 491.xx, 492.x, 496) and were observed during 6-month pre-index and variable (12-18-month) post-index periods. Outcomes were adherence to and discontinuation of therapy, and respiratory-related inpatient, medical, and total health care costs. Adherence was medication possession ratio ≥0.80. Discontinuation, adherence, and costs were analyzed with Cox proportional hazards regression, logistic regression, and generalized linear model regressions, respectively. Regressions controlled for demographic, sociodemographic, and health status factors. RESULTS: The study population comprised 1561 tiotropium and 2976 fluticasone/salmeterol patients. In unadjusted comparisons: 19.5% and 8.5% of tiotropium and fluticasone/salmeterol patients, respectively, were adherent (P < 0.001); tiotropium patients versus fluticasone/salmeterol patients had higher mean respiratory-related pharmacy costs (US$1080 versus US$974, P = 0.002) and health care costs (US$3751 versus US$2932, P = 0.031). Regression analysis showed tiotropium patients were 31.6% less likely to discontinue therapy (95% confidence interval [CI]: 0.64-0.73) and had 2.25 times higher odds of adherence (CI: 1.85-2.73) versus fluticasone/salmeterol patients. The associations between index therapy and costs were not significant. Adherence versus nonadherence was associated with: 46.9% higher health care costs (CI: 1.13-1.91); 37.1% lower medical costs (CI: 0.43-0.91); and 53.4% lower inpatient costs (CI: 0.30-0.72). CONCLUSION: Patients with COPD initiating long-acting bronchodilator therapy were more likely to be adherent to tiotropium than to fluticasone/salmeterol. Adherence to either tiotropium or to fluticasone/salmeterol was associated with lower respiratory-related medical and inpatient costs, and with higher respiratory-related total health care costs.