Psychiatric patients' intensive care admission characteristics, weaning from mechanical ventilation and sedative drug use: A single center retrospective case-control study.

PURPOSE: To describe the characteristics, treatment and outcome, in particular weaning from mechanical ventilation (MV), of critically ill Patients with prior psychiatric conditions (PPC). METHODS: Single center, 6-year, retrospective study comparing critically ill PPC to randomly sex and age matched cohort without PPC (1:1 ratio). Main outcome measure- adjusted mortality rates. Secondary outcome measures- unadjusted mortality, rates of MV, extubation failure and amount/dose of pre-extubation sedatives/analgesics. RESULTS: Included were 214 patients per group. PPC adjusted mortality rates were higher in the ICU (14.0% vs 4.7%; OR 3.058 [95%CI 1.380, 6.774]; p = 0.006) and in-hospital (26.6% vs 13.1%; OR 2.639 [95% CI 1.496, 4.655]; p = 0.001). PPC had higher MV rates (63.6% vs 51.4%; p = 0.011). These patients were more likely to have more than two weaning attempts (29.4% vs 10.9%; p < 0.001), more commonly treated with >2 sedative drugs in the 48-h pre-extubation (39.2% vs 23.3%; p = 0.026) and received more propofol in the 24-h pre-extubation. PPC were more likely to self-extubate (9.6% vs 0.9%; p = 0.004) and had lower likelihood of success in planned extubations (50.0% vs 76.4%; p < 0.001). CONCLUSION: Critically ill PPC had higher mortality rates than their matched counterparts. They also had higher MV rates and were more difficult to wean.

Distribution of Aeration and Pulmonary Blood Volume in Healthy, ARDS and COVID-19 Lungs: A Dual-Energy Computed Tomography Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: Few reports have studied lung aeration and perfusion in normal lungs, COVID-19, and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA). To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19, and controls with a normal DE-CTPA ("healthy lungs"). We hypothesized that each of these conditions has unique ranges of aeration and pulmonary blood volumes. MATERIALS AND METHODS: This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria), and controls. Patients with macroscopic pulmonary embolisms were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios. RESULTS: Included were 20 patients with COVID-19 (10 milds, 10 moderate-severe), six with NC-ARDS, and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24% (IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6 (IQR-33.1-23.2); mild: -30.1 (IQR-33.3-23.4)] and highest in normally aerated areas in NC-ARDS -37.4 (IQR-52.5-30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2-28.5). The median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS. CONCLUSION: Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.

Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program.

OBJECTIVE: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes. RESEARCH DESIGN AND METHODS: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions. RESULTS: Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%. CONCLUSIONS: We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.

Intellectually disabled patients' intensive care admission characteristics, weaning from mechanical ventilation, and sedative drug use: a single-center retrospective case-control study.

BACKGROUND: Intellectually disabled (ID) patients present unique therapeutic challenges. We aimed to describe the characteristics of ID patients admitted to a general intensive care unit (ICU). RESULTS: We conducted a retrospective cohort study comparing critically ill adult ID patients to matched patients without ID (1:2 ratio) in a single ICU (2010-2020). The main outcome measure was mortality. Secondary outcomes included complications during admission and characteristics of weaning from mechanical ventilation. The study and control groups were randomly selected based on similar age and sex. ID patients nonetheless had an average APACHE score of 18.5 ± 8.7 vs. 13.4 ± 8.5 in controls (p < 0.001). ID patients had more hematological (p = 0.04), endocrinological (p < 0.001) and neurological (p = 0.004) comorbidities and used more psychiatric medication before admission. No difference was found in mortality rates. Differences were found as there were more secondary complications, such as pulmonary and sepsis (p < 0.03), frequent requirement of vasopressors (p = 0.001), significantly higher intubation rates with more weaning attempts, tracheostomies and longer ICU and hospital admissions (p < 0.019). CONCLUSIONS: Critically ill adult ID may have more comorbidities and be sicker at the time of admission compared to their age- and sex-matched counterparts. They require more supportive treatment and their weaning from mechanical ventilation may be more challenging.

Homeopathic Treatment for COVID-19-Related Symptoms: A Case Series.

BACKGROUND: Severe acute respiratory syndrome due to coronavirus 2 (SARS CoV-2) is a novel infectious disease, which has quickly developed into a pandemic. The spectrum of COVID-19 symptoms is broad, ranging from a mild, self-limiting respiratory tract illness to severe progressive pneumonia, multi-organ failure and possible death. Despite much effort and multiple clinical trials, there are, to date, no specific therapeutic agents to treat or cure the coronavirus infection. CASE REPORTS: The present paper presents 5 cases of patients with moderate to severe COVID-19 infections, 2 of them hospitalized in the intensive care unit, who were successfully treated with homeopathy. RESULTS: All 5 patients responded to homeopathic treatment in an unexpectedly short time span, improving both physically and mentally. CONCLUSION: The present case series emphasizes the rapidity of response among moderate to severely ill patients to homeopathic treatment, when conventional medical options have been unable to relieve or shorten the disease. The observations described should encourage use of homeopathy in treating patients with COVID-19 during the acute phase of the disease.

COVID-19 classification of X-ray images using deep neural networks.

OBJECTIVES: In the midst of the coronavirus disease 2019 (COVID-19) outbreak, chest X-ray (CXR) imaging is playing an important role in diagnosis and monitoring of patients with COVID-19. We propose a deep learning model for detection of COVID-19 from CXRs, as well as a tool for retrieving similar patients according to the model's results on their CXRs. For training and evaluating our model, we collected CXRs from inpatients hospitalized in four different hospitals. METHODS: In this retrospective study, 1384 frontal CXRs, of COVID-19 confirmed patients imaged between March and August 2020, and 1024 matching CXRs of non-COVID patients imaged before the pandemic, were collected and used to build a deep learning classifier for detecting patients positive for COVID-19. The classifier consists of an ensemble of pre-trained deep neural networks (DNNS), specifically, ReNet34, ReNet50¸ ReNet152, and vgg16, and is enhanced by data augmentation and lung segmentation. We further implemented a nearest-neighbors algorithm that uses DNN-based image embeddings to retrieve the images most similar to a given image. RESULTS: Our model achieved accuracy of 90.3%, (95% CI: 86.3-93.7%) specificity of 90% (95% CI: 84.3-94%), and sensitivity of 90.5% (95% CI: 85-94%) on a test dataset comprising 15% (350/2326) of the original images. The AUC of the ROC curve is 0.96 (95% CI: 0.93-0.97). CONCLUSION: We provide deep learning models, trained and evaluated on CXRs that can assist medical efforts and reduce medical staff workload in handling COVID-19. KEY POINTS: • A machine learning model was able to detect chest X-ray (CXR) images of patients tested positive for COVID-19 with accuracy and detection rate above 90%. • A tool was created for finding existing CXR images with imaging characteristics most similar to a given CXR, according to the model's image embeddings.

Ultra Rapid-Acting Inhaled Insulin Improves Glucose Control in Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: To determine whether the use of an inhaled insulin would improve HbA1c. METHODS: This study was performed in 20 type 2 diabetes mellitus (T2DM) participants with HbA1c values ≥7.5 (58) to ≤11.5% (102 mmol/mol) on a variety of glucose-lowering regimens. Prandial Technosphere insulin (TI) was rapidly titrated based on a treatment algorithm using postprandial blood glucose to calculate premeal doses. A 2-week baseline period was followed by 12 weeks of active treatment with TI. The primary outcome was change in HbA1c. Secondary outcomes included glucose time in range (time in range: 70-180 mg/dL) obtained by a blinded continuous glucose monitoring during the baseline period and at the end of 12 weeks. Goals were to assess how to rapidly and safely initiate TI intensification, determine dosing requirements, and establish an effective dose range in uncontrolled T2DM. RESULTS: Mean HbA1c decreased by -1.6% (-17 mmol/mol) from 9.0% (75 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 12 weeks (P < .0001). Mean time in range increased from 42.2% to 65.7% (P < .0002). Mean prandial doses of TI were 18 or 19 units for all meals. Time below range was 1.1% baseline and 2.6% post treatment (P = .01). CONCLUSION: Treatment with inhaled TI dosed using a simple algorithm improved glycemic control measured by both HbA1c and time in range, with low rates of hypoglycemia. These data add significantly to understanding TI in the management of T2DM patients for whom prandial insulin is a consideration.

Severity of shock, rate of physiological stabilization and organ failure in healthy women admitted to the intensive care unit following major peripartum hemorrhage: A retrospective, descriptive study.

PURPOSE: To describe shock severity, physiological stabilization and organ failure in healthy women admitted to the intensive care unit (ICU) after major peripartum hemorrhage (PPH). MATERIALS AND METHODS: Retrospective, descriptive, single center study. RESULTS: Twenty-nine women median age 33 years (interquartile range [IQR] 30-36) and gravidity 5 pregnancies (IQR 3-9) were studied. One woman died. The median maternal admission hematocrit was 28.8 (IQR 25.7-32.4). Median transfusion rates were nine units of packed red blood cells (IQR 7-12.25), eight fresh frozen plasma (IQR 6-12), 17 platelets (IQR 10-22) and 15 cryoprecipitate (IQR 9.75-20). Blood pressure dropped significantly in the six hours following ICU admission. Nonetheless, lactate decreased from 3.23 mmol/L to 1.54 mmol/L within 24 h of ICU admission, renal and pulmonary function were unaffected and coagulopathy was never observed. Two-thirds of the women underwent hysterectomy. One-third underwent repeated surgery. The median length of ICU stay was <48 h and that of mechanical ventilation was <24 h. Increased transfusion rates correlated with lengthier ICU admission (p ≤ 0.01 regardless of blood product). CONCLUSIONS: Ongoing hemorrhage in women with severe PPH manifests subtly and often requires active intervention. Hemorrhage control is required to achieve physiological stabilization and minimize organ damage.

A Retrospective Study of the Proportion of Women at High and Low Risk of Intrauterine Infection Meeting Sepsis Criteria.

The Surviving Sepsis Campaign recently recommended that qSOFA not be used as a single parameter for identification of sepsis. Thus, we evaluated the efficacy of SIRS and qSOFA scores in identifying intrauterine infection. This case-control study evaluates SIRS and qSOFA criteria fulfillment in preterm premature rupture of membranes (n = 453)-at high infection risk-versus elective cesarean-at low infection risk (n = 2004); secondary outcomes included intrauterine infection and positive culture rates. At admission, 14.8% of the study group and 4.6% of control met SIRS criteria (p = 0.001), as did 12.5% and 5.5% on post-operation day (POD) 1 (p = 0.001), with no significant differences on POD 0 or 2. Medical records did not suffice for qSOFA calculation. In the study group, more cultures (29.8% versus 1.9%-cervix; 27.4% versus 1.1%-placenta; 7.5% versus 1.7%-blood; p = 0.001-all differences) and positive cultures (5.5% versus 3.0%-urine-p = 0.008; 4.2% versus 0.2%-cervix-p = 0.001; 7.3% versus 0.0%-placenta-p = 0.001; 0.9% versus 0.1%-blood-p = 0.008) were obtained. Overall, 10.6% of the study group and 0.4% of control met the intrauterine infection criteria (p = 0.001). Though a significant difference was noted in SIRS criteria fulfillment in the study group versus control, there was considerable between-group overlap, questioning the utility of SIRS in intrauterine infection diagnosis. Furthermore, the qSOFA scores could not be assessed.

Spatial variation in exploited metapopulations obscures risk of collapse.

Unanticipated declines among exploited species have commonly occurred despite harvests that appeared sustainable prior to collapse. This is particularly true in the oceans where spatial scales of management are often mismatched with spatially complex metapopulations. We explore causes, consequences, and potential solutions for spatial mismatches in harvested metapopulations in three ways. First, we generate novel theory illustrating when and how harvesting metapopulations increases spatial variability and in turn masks local-scale volatility. Second, we illustrate why spatial variability in harvested metapopulations leads to negative consequences using an empirical example of a Pacific herring metapopulation. Finally, we construct a numerical management strategy evaluation model to identify and highlight potential solutions for mismatches in spatial scale and spatial variability. Our results highlight that spatial complexity can promote stability at large scales, however, ignoring spatial complexity produces cryptic and negative consequences for people and animals that interact with resources at small scales. Harvesting metapopulations magnifies spatial variability, which creates discrepancies between regional and local trends while increasing risk of local population collapses. Such effects asymmetrically impact locally constrained fishers and predators, which are more exposed to risks of localized collapses. Importantly, we show that dynamically optimizing harvest can minimize local risk without sacrificing yield. Thus, multiple nested scales of management may be necessary to avoid cryptic collapses in metapopulations and the ensuing ecological, social, and economic consequences.

Real-world evidence in diabetes: relevance to clinical practice.

Real-world studies may be distinguished from traditional randomized controlled trials (RCTs) based on the study population and the setting in which the research is conducted. While RCTs are the gold standard for evaluating the efficacy and safety of new therapeutic interventions, they are typically conducted in specialized environments that may lack the everyday reality of clinical, home, and community settings. There is often a gap between efficacy shown in RCTs and the effectiveness observed in real-world settings. Real-world studies and resultant real-world data can be used to develop real-world evidence (RWE). RWE adds to the evidence from RCTs by providing additional results obtained from a broader patient population outside the constraints of RCTs to evaluate what is happening in usual clinical practice. Thus, RWE is useful in determining the effectiveness and safety of an intervention in clinical practice, and it can also provide information on health care resource utilization and costs, which are not typically evaluated in RCTs.

Duodenal mucosal resurfacing: proof-of-concept, procedural development, and initial implementation in the clinical setting.

BACKGROUND AND AIMS: We aimed to develop duodenal mucosal resurfacing (DMR), a minimally invasive upper endoscopic hydrothermal ablation procedure, to treat insulin-resistant metabolic diseases. METHODS: We completed a sham-controlled, rodent proof-of-concept study and longitudinal safety study in pigs to demonstrate feasibility to test DMR in humans. Subsequently, the DMR procedure was implemented in an open-label first-in-human (FIH) study of safety and efficacy in patients with type 2 diabetes (T2D). RESULTS: In rats, duodenal abrasion reduced hyperglycemia by 59 mg/dL on average, compared with no change from baseline in the sham treatment arm (P < .05). In pigs, the balloon catheter successfully and safely delivered hydrothermal ablation to the duodenal mucosa and superficial submucosa. Complete mucosal healing was demonstrated by week 6. In the FIH study, hydrothermal ablation was successfully administered with no evidence of perforation, pancreatitis, or hemorrhage. Duodenal biopsy specimens obtained 3 months postprocedure demonstrated full mucosal regrowth. No inflammation was observed, and there was minimal-to-mild collagen banding deposition observed in a proportion of ablation site biopsy specimens with no evidence of fibrotic scarring. Glycemic and hepatic measures improved through 6 months of follow-up. CONCLUSIONS: DMR shows potential as an endoscopic intervention that improves glycemic and hepatic parameters in patients with T2D. Further mechanistic and clinical studies are underway to further explore DMR as a treatment for metabolic disease.

Predictors and Clinical Outcomes of Treatment Intensification in Patients With Type 2 Diabetes Uncontrolled on Basal Insulin in a Real-World Setting.

OBJECTIVE: To understand factors associated with intensification of basal insulin therapy and treatment impact on clinical outcomes in patients with type 2 diabetes (T2D). METHODS: In this retrospective, observational study of the Practice Fusion electronic health record database, eligible patients were adults with T2D, ≥1 basal insulin prescription and office visit in the 6 months before a glycated hemoglobin A1c (A1C) test >7.0% (index date), and no other injectable prescriptions in the 12 months before the index date. Patients were categorized to intensifiers with injectables (rapid-acting insulin [RAI], glucagon-like peptide-1 receptor agonist [GLP-1 RA], or other injectables) or nonintensifiers with injectables (including no change, adding an oral antidiabetes drug, or changing basal insulin dose). Principal outcomes were A1C change, hypoglycemia incidence, and change in body weight. RESULTS: Among 14,653 patients, 2,121 (14.5%) and 12,532 (85.5%) were categorized as intensifiers and nonintensifiers with injectables, respectively. Compared with nonintensifiers, intensifiers were more likely to have an endocrinologist as the prescribing physician (odds ratio [OR], 2.52 [95% confidence interval (CI), 2.16 to 2.94]), hypertension (OR, 1.26 [95% CI, 1.08 to 1.47]), higher baseline A1C (OR, 1.22 [95% CI, 1.17 to 1.26]), obesity (OR, 1.17 [95% CI, 1.01 to 1.36]), and higher body mass index (OR, 1.02 [95% CI, 1.01 to 1.03]). In GLP-1 RA intensifiers, the baseline use of dipeptidyl peptidase-4 inhibitors increased the likelihood of intensification. GLP-1 RA intensifiers had equivalent glycemic control to RAI or other injectables, with a nonsignificantly lower risk of hypoglycemia and reduction in body weight. CONCLUSION: Addition of GLP-1 RA to basal insulin may be an effective strategy for overcoming clinical inertia with injectable therapy in patients with T2D. ABBREVIATIONS: A1C = glycated hemoglobin A1c; BMI = body mass index; CI = confidence interval; DCSI = Diabetes Complications Severity Index; DPP-4 = dipeptidyl peptidase-4; EHR = electronic health record; GLP-1 RA = glucagon-like peptide-1 receptor agonist; ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification; ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification; OAD = oral antidiabetes drug; OR = odds ratio; RAI = rapid-acting insulin; SGLT-2 = sodium-glucose cotransporter-2; T2D = type 2 diabetes.

Real-world clinical responses in patients with type 2 diabetes mellitus adding exenatide BID (EBID) or mealtime insulin to basal insulin: a retrospective study using electronic medical record data.

AIM: Exenatide twice daily (EBID) and mealtime insulin are effective add-on therapies to basal insulin for type 2 diabetes patients in clinical trials. This study used electronic medical record (EMR) data to evaluate analogous real-world clinical responses. MATERIALS AND METHODS: Adult patients initiating EBID or mealtime insulin as add-on to basal insulin during January 2008-March 2013 were identified in a US EMR database. EBID patients were propensity score matched 1:1 to mealtime insulin patients. Cohorts were followed for 12 months before (baseline) and 6 months after the index. A1C, hypoglycemic events, change in weight, and other clinical measures were evaluated by A1C attainment level (<6.5, < 7, < 7.5, <8, <9%) and baseline A1C. RESULTS: In total, 1249 EBID patients were matched to 1249 mealtime insulin patients. During follow-up, the percentage reaching A1C levels was similar for EBID vs mealtime insulin cohorts for all attainment levels (<7%: 27.8% vs 24.2%; < 9%: 79.7% vs 79.2%; p = NS). The percentage reaching A1C < 7% was similar for both cohorts with different baseline A1C. EBID patients had less hypoglycemia at all attainment levels (3.1% vs 11.1% [<6.5%]; 2.5% vs 4.7% [<9%]; all p < .03) and more weight loss (-9.0 vs -3.2 lb [<6.5%]; -3.4 vs +0.8 lb [<9%]; all p < .01). CONCLUSIONS: EBID added to basal insulin was as effective in a real-world setting as mealtime insulin added to basal insulin in reducing A1C, with less weight gain and less hypoglycemia for a wide range of A1C attainment levels and baseline values.

COMPARING CLINICAL OUTCOMES AND COSTS FOR DIFFERENT TREATMENT INTENSIFICATION APPROACHES IN PATIENTS WITH TYPE 2 DIABETES UNCONTROLLED ON BASAL INSULIN: ADDING GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS VERSUS ADDING RAPID-ACTING INSULIN OR INCREASING BASAL INSULIN DOSE.

OBJECTIVE: Not all patients with type 2 diabetes achieve recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes. METHODS: This retrospective analysis of health insurance claims data in the U.S. MarketScan database compared glycemic control and healthcare resource utilization and costs 12 months after adding a GLP-1 RA to BI versus adding a RAI or increasing BI doses. Propensity score matching was used in the comparative effectiveness analysis. RESULTS: A total of 8,034 patients underwent treatment intensification within 6 months of showing poor glycemic control; 4,134 patients had their BI dose adjusted, and 2,076 and 331 received RAI and GLP-1 RA, respectively. A1C changes were similar for the GLP-1 RA and RAI cohorts but higher for the GLP-1 RA versus the dose-adjustment group. The hypoglycemia rate was lower after adding GLP-1 RA versus RAI or increasing BI dose. No overall changes in utilization of healthcare resources or diabetes-related costs were observed between intensification strategies, although prescription costs were higher for the GLP-1 RA cohort. CONCLUSION: BI in combination with GLP-1 RAs appears to be an effective intensification strategy, further reducing A1C levels and hypoglycemia frequency compared to increasing BI doses. GLP-1 RA addition also decreases hypoglycemia frequency versus BI dose increases and RAI addition, without raising overall healthcare costs. ABBREVIATIONS: A1C = hemoglobin A1c; BI = basal insulin; CAD = coronary artery disease; ED = emergency department; FPG = fasting plasma glucose; GLP-1 RA = glucagon-like peptide 1 receptor agonist; ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; NPH = neutral protamine Hagedorn; OAD = oral antidiabetes drug; PSM = propensity score matching; RAI = rapid-acting insulin; T2D = type 2 diabetes.

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. OBJECTIVE: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. METHODS: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D. RESULTS: Of the 1303 papers identified, 57 met the prespecified criteria for a high-quality clinical trial or retrospective study. The efficacy and tolerability of approved GLP-1RAs (exenatide twice daily or once weekly, dulaglutide, liraglutide, lixisenatide, and albiglutide) were compared with insulin products (23 prospective studies + seven retrospective studies), dipeptidyl peptidase-4 inhibitors (11 prospective studies + three retrospective studies), sulfonylureas (nine prospective studies + one retrospective study), thiazolidinediones (five prospective studies), and metformin (two prospective studies). GLP-1RAs are effective as a second-line therapy in improving glycemic parameters in patients with T2D. Reductions in glycated hemoglobin from baseline with GLP-1RAs tended to be greater or similar compared with insulin therapy. GLP-1RAs were consistently more effective in reducing body weight than most oral glucose-lowering drugs and insulin and were associated with lower hypoglycemia risk versus insulin or sulfonylureas. GLP-1RAs improved cardiovascular risk factors, and preliminary data suggest they improve cardiovascular outcomes in patients with T2D compared with oral glucose-lowering drugs. However, results from ongoing studies are awaited to confirm these early findings. CONCLUSION: This systematic review found that GLP-1RAs are an effective class of glucose-lowering drugs for T2D.

A real-world study of treatment patterns and outcomes in US managed-care patients with type 2 Diabetes initiating injectable therapies.

AIMS: Examine real-world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study. MATERIALS AND METHODS: Linked insurance claims and medical record data were collected from 2 large US health insurers (April 1, 2010 to March 31, 2012) of T2DM adults initiating treatment with glargine (GLA) or liraglutide (LIRA). Baseline characteristics were examined and changes in 12-month follow-up outcomes were described for both treatment groups: HbA1c, weight change, hypoglycaemia, persistence, healthcare utilisation and costs. RESULTS: A total of 4490 patients were included (GLA, 2116; LIRA, 2374). At baseline, GLA patients had significantly higher HbA1c vs LIRA patients (9.72% vs 8.19%; P < .001), lower likelihood of having HbA1c < 7% (7.1% vs 23.8%; P < .001), lower bodyweight (100.9 kg vs 110.9 kg, P < .001), higher Charlson Comorbidity Index score (0.88 vs 0.63; P < .001), and higher diabetes-related costs ($3492 vs $2089; P < .001), respectively. During 12-months of follow-up, treatment persistence was 64%, mean HbA1c reduction was -1.24% and weight change was + 1.17 among GLA patients, and was 49%, -0.51% and -2.74 kg, respectively, among LIRA patients. Diabetes-related costs increased significantly from baseline to follow-up for LIRA patients ($2089 vs $3258, P < .001) but not for GLA patients ($3492 vs $3550, P = .890). CONCLUSIONS: There were clinically relevant baseline differences in both groups, suggesting that GLA and LIRA are prescribed for different patient groups, and highlighting that efficacy results from clinical trials do not always translate into real-world practice. Significant increases in healthcare costs were observed in the LIRA group, warranting further cost-effectiveness analysis.

Practical combination therapy based on pathophysiology of type 2 diabetes.

Type 2 diabetes is a complex, chronic, and progressive condition that often necessitates the use of multiple medications to achieve glycemic goals. Clinical guidelines generally recommend intensifying pharmacotherapy if glycemic goals are not achieved after 3 months of treatment. However, for many patients with type 2 diabetes, treatment intensification is delayed or does not occur. Initiating combination therapy early in the disease course has the potential to delay disease progression and improve patient outcomes. Guidelines generally provide a list of agents that may be used in combination regimens and emphasize individualization of treatment. The purpose of this review is to discuss the rationale for combination therapy, considering treatment effects on pathophysiologic aspects of type 2 diabetes and individual drug profiles. The combination of newer antidiabetes therapies with complementary mechanisms of action provides the opportunity to target multiple sites of tissue, organ, and cellular dysfunction.

Impact of symptomatic upper respiratory tract infections on insulin absorption and action of Technosphere inhaled insulin.

OBJECTIVE: Uncomplicated, acute upper respiratory tract infections (URTIs) occur in patients with diabetes at a similar frequency to the general population. This study (NCT00642681) investigated the effect of URTIs on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of Technosphere inhaled insulin (TI) in patients with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a phase 2 study conducted in patients who developed a URTI while being treated with TI in a phase 3 study (N=20, mean age 50 years, 60% men). Patients underwent two 4-hour meal challenges, during which blood samples were drawn to measure serum fumaryl diketopiperazine (FDKP; the excipient representing an essential part of TI), serum insulin, serum C-peptide, and plasma glucose. The primary outcome was the ratio of serum FDKP area under the concentration-time curve from 0 to 240 min (AUC0-240 min) during URTI and after clinical resolution of URTI symptoms (≥15 to ≤45 days). RESULTS: No significant differences in PK parameters were seen during URTI versus post-URTI for FDKP. The ratio of serum FDKP AUC0-240 min during URTI and post-URTI was 1.1 (SD 0.6), p=0.4462. Plasma glucose concentrations during each 4-hour meal challenge were similar, showing small non-significant differences. No adverse events, including hypoglycemia, occurred during meal challenge visits. CONCLUSIONS: Development of an active, symptomatic URTI during treatment with TI had no significant impact on the PK/PD properties of TI, suggesting that no adjustment in prandial insulin dosing is needed. However, if patients are unable to conduct proper inhalation, they should administer their prandial insulin subcutaneously. TRIAL REGISTRATION NUMBER: NCT00642681; Results.