Long-acting Agents Research Articles

Suboptimal Adherence to Antihypertensive Treatment: Causes and Management

Suboptimal adherence to antihypertensive treatment is very common and is associated with poor control of blood pressure and increased risk for cardiovascular events. Therefore, frequent evaluation of compliance is essential in all hypertensive patients. Simplifying treatment regimens, using fixed-dose combinations and long-acting agents improves adherence, facilitates achievement of treatment targets and reduces cardiovascular morbidity and healthcare expenditures. Accordingly, physicians should be educated to implement these changes in hypertensive patients, particularly in those who require multiple antihypertensive agents to achieve blood pressure controls and in those who receive additional medications for comorbidities.

Glucagon-like peptide-1 receptor agonists in type 2 diabetes treatment: are they all the same?

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an important class of drugs with a well-established efficacy and safety profile in patients with type 2 diabetes mellitus. Agents in this class are derived from either exendin-4 (a compound present in Gila monster venom) or modifications of human GLP-1 active fragment. Differences among these drugs in duration of action (ie, short-acting vs long-acting), effects on glycaemic control and weight loss, immunogenicity, tolerability profiles, and administration routes offer physicians several options when selecting the most appropriate agent for individual patients. Patient preference is also an important consideration. The aim of this review is to discuss the differences between and similarities of GLP-1 RAs currently approved for clinical use, focusing particularly on the properties characterising the single short-acting and long-acting GLP-1 RAs rather than on their individual efficacy and safety profiles. The primary pharmacodynamic difference between short-acting (ie, exenatide twice daily and lixisenatide) and long-acting (ie, albiglutide, dulaglutide, exenatide once weekly, liraglutide, and semaglutide) GLP-1 RAs is that short-acting agents primarily delay gastric emptying (lowering postprandial glucose) and long-acting agents affect both fasting glucose (via enhanced glucose-dependent insulin secretion and reduced glucagon secretion in the fasting state) and postprandial glucose (via enhanced postprandial insulin secretion and inhibition of glucagon secretion). Other advantages of long-acting GLP-1 RAs include smaller fluctuations in plasma drug concentrations, improved gastrointestinal tolerability profiles, and simpler, more convenient administration schedules (once daily for liraglutide and once weekly for albiglutide, dulaglutide, the long-acting exenatide formulation, and semaglutide), which might improve treatment adherence and persistence.

Effects of a single long-acting muscarinic antagonist agent and a long-acting muscarinic antagonist/long-acting β2-adrenoceptor agonist combination on lung function and symptoms in untreated COPD patients in Japan.

BackgroundA large body of evidence suggests that long-acting β2-adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) combinations induce a strong synergistic bronchodilatory effect in human isolated airways. Moreover, a recent post hoc analysis demonstrated clinical synergism between LABAs and LAMAs, which induces a synergistic improvement not only in lung function but also in dyspnea in COPD patients.AimThe aim of this study is to examine the baseline factors related to improvement in lung function or clinical symptoms that results from the administration of LAMA or LAMA/LABA and to compare the differences in improvement in lung function or clinical symptoms between LAMA and LAMA/LABA.MethodsAmong 829 patients with COPD who were treated with LAMA or LAMA/LABA in our hospital, 112 patients (aged 40–89 years) matched the criteria. Of these 112 patients, 71 received LAMA (LAMA group) and 41 received LAMA/LABA (LAMA/LABA group) as the initial treatment. Various examination results such as lung function test values, symptom change, and frequency of exacerbations were compared between the two groups.ResultsCompared with the monotherapy, the combination therapy significantly improved the FEV1, inspiratory capacity (IC), and total COPD assessment test (CAT) scores. Comparing the improvement in each domain of the CAT produced by the combination therapy with that of the monotherapy, larger improvements were found for the domains of going out and sleeping. The frequency of exacerbations during the 24 weeks was significantly lower in the combination therapy group than in the LAMA monotherapy group (P=0.034). Although no relationship was found between improvement in FEV1 and any pretreatment factors in the LAMA/LABA group, the improvement in the CAT score was strongly related to the baseline CAT score, smoking index, and air trapping index (P-value <1×10−4).ConclusionIn this study of clinical practice, we found that LAMA/LABA combination therapy improved the clinical symptoms of COPD and IC and that the effects of the combination therapy were consistent with those observed in previous clinical trials.

Enhanced intestinal 2-deoxy-2-[18F]fluoro-D-glucose uptake under metformin is not fully suppressed by loperamide.

This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Mean 18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and 18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of 18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. 18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced 18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Metformin increased 18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of 18F-FDG.

Ropivacaine Protects against Memory Impairment and Hippocampal Damage in a Rat Neurodegeneration Model

Background: Ropivacaine, a long-acting amide local anesthetic agent, has been demonstrated to inhibit glutamatergic transmission. Glutamate neurotoxicity plays a pivotal role in the pathogenesis of brain disorders. The purpose of this study is to investigate the neuroprotective effect of ropivacaine against brain damage induced by kainic acid (KA), an analogue of glutamate. Methods: Rats were injected with ropivacaine (0.4 or 2 mg/kg, intraperitoneal) 30 min before KA treatment (15 mg/kg, intraperitoneal). KA-induced memory impairment was evaluated using the Morris water maze test. Extracellular hippocampal glutamate levels were assessed using high-performance liquid chromatography. Neuronal death was verified using Fluoro-Jade B and neutral red staining, and apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was conducted to assay the levels of activated (cleaved) caspase-3 and the phosphorylation of different mitogen-activated protein kinases (MAPKs). ­Results: Ropivacaine pretreatment effectively prevented KA-induced memory impairment. KA-induced elevations of ­glutamate release in rat hippocampi were inhibited by pretreatment with ropivacaine. Histopathological and TUNEL staining analyzes showed that ropivacaine inhibited KA-induced neuronal death and apoptosis in the hippocampal CA3 region. KA-induced caspase-3 activation and MAPKs phosphorylation in the hippocampus were also reduced by ropivacaine pretreatment. Conclusions: This study ­demonstrates that ropivacaine executes a protective action against KA-induced neuronal damage and apoptosis in vivo. Protective effects may be caused by glutamate level reduction, caspase-3 activation suppression, and MAPKs phosphorylation reduction. Our findings indicate that ropivacaine can benefit prevention or treatment of glutamate excitotoxicity-related neurodegenerative diseases.

The delicate choice of optimal basic therapy for multimorbid older adults: A cross-sectional survey.

Clinical practice guidelines are useful to suggest pharmacological therapies for the treatment of single chronic diseases. However, there is little guidance for multimorbidity, and specific quality measures for people with multimorbidity that can be used at a population level are lacking. To describe what pharmacists and geriatricians consider to be an optimal basic pharmacological therapy for an older individual with type 2 diabetes (DM), chronic obstructive pulmonary disease (COPD) and heart failure (HF). An online cross-sectional survey among 162 pharmacists and geriatricians, in Quebec, Canada, was performed. Participants were invited to choose, from a list of 32 medications or classes, the optimal basic therapy for an individual aged 65-75 years with the 3 chronic diseases. Descriptive statistics were used to calculate the median number of medications chosen and the proportions of participants who chose each medication, according to the participant's specialty. A Kruskall-Wallis test was performed to detect whether there were differences in the median number of medications recommended according to speciality. There was little consensus on the optimal basic pharmacological therapy for this hypothetical multimorbid individual, with 157 different combinations provided by the 162 participants. Nevertheless, 5 classes were chosen by at least 75% of the participants: metformin, long-acting anticholinergic agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), beta-blockers, and short-acting beta-agonists. The median number of recommended medications was 10 (interquartile range [IQR]: 6-13). There was a statistically significant difference between specialties (p = 0.0396). Geriatricians recommended the lower median number of medications, 7 (IQR: 5-10). At least half of the participants considered polypharmacy (≥10 medications) inevitable for an optimal basic treatment of DM, COPD and HF. The heterogeneity of responses raises issues when considering quality indicators in population-based studies.

Asthma Guidelines Priority Topic: Long-Acting Anti-Muscarinic Agents in Asthma Management as Add-On to Inhaled Corticosteroids

The National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma are slated to be updated on 6 topic areas. This review summarizes the findings for the cha...

PUK5 - The Financial Impact of Introducing Darbepoetin Alfa (DA) as a New Long-Acting Erythropoiesis-Stimulating Agent Alternative for Non-Adherent Peritoneal Dialysis Patients in the Ministry of Health (MOH) Malaysia

PUK5 - The Financial Impact of Introducing Darbepoetin Alfa (DA) as a New Long-Acting Erythropoiesis-Stimulating Agent Alternative for Non-Adherent Peritoneal Dialysis Patients in the Ministry of Health (MOH) Malaysia

Rational design of dimeric lipidated Xenopus glucagon-like peptide 1 analogues as long-acting antihyperglycaemic agents

Dimerization is viewed as an effective means to enhance the binding affinity and therapeutic potency of peptides. Both dimerization and lipidation effectively prolong the half-life of peptides in vivo by increasing hydrodynamic size and facilitating physical interactions with serum albumin. Here, we report a novel method to discover long-acting glucagon-like peptide 1 (GLP-1) analogues by rational design based on Xenopus GLP-1 through a combined dimerization and lipidization strategy. On the basis of our previous structure analysis of Xenopus GLP-1, palmitic acid and a C-terminal Cys were firstly introduced into two Xenopus GLP-1 analogues (1 and 2), and the afforded 3 and 4 were further reacted with bis-maleimide amine to afford two dimeric lipidated Xenopus GLP-1 analogues (5 and 6). The in vitro and in vivo biological activities of 5 and 6 were significantly improved as compared with their monomers. Moreover, the selected compound 6 showed greater hypoglycemic and insulinotropic activities than liraglutide even when the dose of 6 was reduced to half in db/db mice. Pharmacokinetic test revealed that 6 had a ∼ 3-fold longer half-life than liraglutide in Kunming mice and SD rats, and the longer half-life of 6 led to excellent long-acting hypoglycemic effects as confirmed by two different pharmacological methods conducted on db/db mice. Finally, a 7 weeks chronic study conducted on db/db mice demonstrated the better therapeutic efficacies of 6 on glucose tolerance normalization, HbA1c reduction and pancreas islets protection than liraglutide. The present research showed that combined dimerization and lipidization is effective when applied to Xenopus GLP-1 analogue to develop novel GLP-1 analogue for the treatment of type 2 diabetes. In addition, the promising preclinical data of 6 suggested the therapeutic potential of 6 as a novel anti-diabetic agent.

Anaesthesiologist's Approach to Awake Craniotomy.

Awake craniotomy, which was initially used for the surgical treatment of epilepsy, is performed for the resection of tumours in the vicinity of some eloquent areas of the cerebral cortex which is essential for language and motor functions. It is also performed for stereotactic brain biopsy, ventriculostomy, and supratentorial tumour resections. In some institutions, avoiding risks of general anaesthesia, shortened hospitalization and reduced use of hospital resources may be the other indications for awake craniotomy. Anaesthesiologists aim to provide safe and effective surgical status, maintaining a comfortable and pain-free condition for the patient during surgical procedure and prolonged stationary position and maintaining patient cooperation during intradural interventions. Providing anaesthesia for awake craniotomy require scalp blockage, specific sedation protocols and airway management. Long-acting local anaesthetic agents like bupivacaine or levobupivacaine are preferred. More commonly, propofol, dexmedetomidine and remifentanyl are used as sedative agents. A successful anaesthesia for awake craniotomy depends on the personal experience and detailed planning of the anaesthetic procedure. The aim of this review was to present an anaesthetic technique for awake craniotomy under the light of the literature.

Wednesday, September 26, 2018 1:00 PM – 2:00 PM Interventional Pain Management: 32. Spinal anesthesia and thoracolumbar interfascial plane block provide optimum analgesia for lumbar fusion surgery

BACKGROUND CONTEXT Spinal anesthesia (SA) has been shown in several studies to be a viable alternative to general anesthesia (GA) in laminectomies and discectomies. In particular, lower postoperative pain has been consistently demonstrated with SA. However, very few spine surgeons have extended the use of SA to lumbar fusion surgery, and few studies to date have documented its use in the literature. The authors posit that SA may lead to lower postoperative pain than GA, and have implemented use of a novel thoracolumbar interfascial plane (TLIP) block for additional long-lasting analgesia. PURPOSE The purpose of this study is to compare the use of GA and SA in lumbar fusion surgery in terms of acute postoperative outcomes, and to determine the analgesic value of the TLIP block. STUDY DESIGN/SETTING Retrospective chart review. PATIENT SAMPLE A total of 82 consecutive patients who underwent 1- or 2-level minimally invasive transforaminal lumbar interbody fusion by a single surgeon from 2015 to 2018. OUTCOME MEASURES A review of demographic information and postoperative records was conducted for the following outcome measures: pain (VAS score), opioid requirement, nausea/vomiting, PACU time, days of admission, adverse hospital event (PE, MI, COPD exacerbation, etc), ambulation during initial PT evaluation, discharge status, 30-day return to ED, 30-day readmission. METHODS The authors retrospectively reviewed the charts of all patients who underwent 1- or 2-level minimally invasive transforaminal lumbar interbody fusion (TLIF) surgery by a single surgeon, at a single institution, from 2015 to 2018. TLIP block consisted of injection of a long-acting local anesthetic agent in liposomal suspension into the fascial plane between the multifidus and longissimus muscles. Patients were placed into 1 of 3 groups based on anesthetic modality: (1) GA; (2) SA; (3) SA+TLIP block. RESULTS A total of 29 patients received SA, 46 received GA, and seven received SA+TLIP block. All groups were similar in terms of age, gender, BMI, number of levels operated upon, preoperative diagnosis, and ASA physical score. Both the SA and SA+TLIP groups experienced significantly lower max postoperative pain scores (3.31±1.65/10 and 1.71±2.71/10, respectively) than the GA group (5.96±0.84/10, p CONCLUSIONS To our knowledge, SA is almost never used in lumbar fusion and the use of the preoperative TLIP block is a novel concept in spine surgery. In this retrospective study, we demonstrate that use of SA in TLIF surgery can lead to lower pain scores and opioid usage in the PACU, while producing similar postoperative outcomes. Addition of the TLIP block may lead to even lower pain and opioid usage over SA alone, though our sample size was not large enough to achieve significance. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Rilpivirine long-acting for the prevention and treatment of HIV infection.

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor approved for the treatment of HIV in combination with other antiretrovirals (ARV). The development of the long-acting formulation of rilpivirine (RPV-LA) and its use in clinical settings is the subject of this review. In 2017, the results of the phase IIb study LATTE2 have been published. This study demonstrated that the combination of RPV-LA with a second long-acting agent (cabotegravir) administered intramuscularly every 4--8 weeks was similar in virologic suppression rates to standard of care ARV treatment. RPV-LA is an injectable nanoparticle suspension for intramuscular use. Phase I studies in healthy volunteers demonstrated that RPV-LA, administered at doses between 600 and 1200 mg, was well tolerated and effective in maintaining satisfactory drug concentrations in plasma, vaginal secretions and rectal tissue compartments for at least 4 weeks. RPV-LA efficacy was also shown in a phase II clinical trial in HIV infected patients and phase III studies are currently ongoing. Most study participants stated that they would use or continue using injectables, both in HIV treatment and prevention settings. Long-acting injectable ARVs have the potential to improve the convenience of HIV drug regimens.

Optimising treatment for severe asthma.

The treatment landscape in severe asthma is changing rapidly, with multiple new therapies emerging that promise to transform patient outcomes. In a patient who is not responding to conventional therapy with inhaled corticosteroids and long-acting β2-agonists, it is important to first consider if the diagnosis of asthma is correct and, second, to reflect on whether readily modifiable factors are contributing to poor asthma control. In selected patients it may be appropriate to consider a modified n-of-1 trial of add-on therapies such as long-acting anti-muscarinic agents, leukotriene blockers, theophylline or low dose macrolide antibiotics. A number of monoclonal antibodies are now available that target the molecular pathways that contribute to asthma pathogenesis, and more such agents are likely to emerge in the near future. These biologicals can be transformative in selected patients, markedly reducing the frequency of asthma exacerbations, and allowing many patients to reduce or eliminate their use of long term oral corticosteroids. If the promise of personalised treatment is to be fully realised, it is important that better methods are developed to target these new and expensive treatments to patients most likely to respond. The ultimate goal of inducing remission or cure of asthma is still some distance away.

A Comparison of Two Methods of Regional Anesthesia

Category: Other Introduction/Purpose: Poorly controlled post-operative pain is a common cause of patient dissatisfaction. With future emphasis on value-based medicine, optimization of cost-effectiveness and patient satisfaction is critical. Popliteal and saphenous nerve blocks are routinely use in foot and ankle orthopaedic surgery and have become the gold standard for immediate post-operative analgesia. Traditionally a single long-acting local anesthetic agent is utilized which achieves analgesia for 6-24 hours. Recent evidence has shown that multimodal anesthesia with combined anesthetic agents remains effective for a longer duration compared to single-medication nerve blocks. The purpose of this study is to determine if patients undergoing foot and ankle surgery safely benefit from multi-modal compared with traditional single-medication nerve blocks. Methods: This was a two-armed, prospective, randomized, double-blinded study. The study population consisted of 70 patients from a single institution undergoing foot and ankle surgery by two fellowship-trained orthopaedic foot and ankle surgeons. 34 patients received a local anesthetic only popliteal and saphenous nerve block (Bupivacaine) and the other 36 patients received a triple additive nerve block (Dexamethasone, Clonidine, and Buprenorphine) in addition to Bupivacaine. Pre- and Post-operative assessments were performed to determine VAS pain scores, numbness, duration of anesthesia, patient satisfaction with analgesia, and oral pain medication use. Results: Triple additive (TA) nerve block mean duration to onset of pain was longer than for single agent (LA) nerve blocks (40.2 hrs vs 24.3 hrs respectively). Time to complete block resolution was also longer for the TA nerve blocks (82.3 hours) compared to LA blocks (38.7 hrs). 17/34 TA block patients had residual numbness at 1 week compared to 5/36 LA block patients. However, by 3 months there was no difference (8/34 TA and 7/36 LA). There was no significant difference in VAS scores or patient satisfaction rates at 1 week or 3 months. 7/34 TA block patients required narcotic refills compared to 6/36 LA block patients. There was no significant difference in complications between the groups. Conclusion: Triple agent nerve blocks give a longer duration of effective postoperative analgesia compared to single agent blocks. There was a higher rate of lingering numbness in the triple agent blocks at one week but not at 3 months. Patient satisfaction was very high for both groups regardless of their VAS pain scores. Triple agent nerve blocks demonstrate equivalent safety compared with single agent nerve blocks.

Learning optimal opioid prescribing and monitoring: a simulation study of medical residents.

ObjectiveHospitalized patients often receive opioids. There is a lack of consensus regarding evidence-based guidelines or training programs for effective management of pain in the hospital. We investigated the viability of using an Internet-based opioid dosing simulator to teach residents appropriate use of opioids to treat and manage acute pain.Materials and methodsWe used a prospective, longitudinal design to evaluate the effects of simulator training. In face-to-face didactic sessions, we taught 120 (108 internal medicine and 12 family medicine) residents principles of pain management and how to use the simulator. Each trainee completed 10 training and, subsequently, 5 testing trials on the simulator. For each trial, we collected medications, doses, routes and times of administration, pain scores, and a summary score. We used mixed-effects regression models to assess the impact of simulation training on simulation performance scores, variability in pain score trajectories, appropriate use of short- and long-acting opioids, and use of naloxone.ResultsTrainees completed 1582 simulation trials (M = 13.2, SD = 6.8), with sustained improvements in their simulated pain management practices. Over time, trainees improved their overall simulated pain management scores (b = 0.05, P < .01), generated lower pain score trajectories with less variability (b = −0.02, P < .01), switched more rapidly from short-acting to long-acting agents (b = −0.50, P < .01), and used naloxone less often (b = −0.10, P < .01).Discussion and conclusionsTrainees translated their understanding of didactically presented principles of pain management to their performance on simulated patient cases. Simulation-based training presents an opportunity for improving opioid-based inpatient acute pain management.

A quick scoping review of efficacy, safety, economic, and health-related quality-of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia and chronic kidney disease anemia.

Erythropoiesis-stimulating agents (ESAs) are man-made forms of erythropoietin used in the treatment of anemia. This quick-scoping review of systematic literature reviews (SLRs) was conducted to define the clinical, economic, and health-related quality of life (HRQoL) outcomes for short-acting and long-acting ESAs in patients with chronic kidney disease-induced anemia (CKD-IA) and patients with chemotherapy-induced anemia (CIA). Embase, Medline, and the Cochrane Database of Systematic Reviews were searched from their establishment until October 2017. SLRs related to the use of short-acting and long-acting ESAs in the treatment of CIA and CKD-IA were included. Forty-eight studies met the inclusion criteria. The evidence suggests little difference in efficacy, HRQoL, and safety outcomes among ESA types. Cost-effectiveness and market price are likely to become determining factors driving the choice of agent. Comparative studies and costing models accounting for the utilization of biosimilars are needed to establish which ESAs are more cost-effective.

Attitudes of physicians from 10 European countries on adherence and how treatment modalities in ABSSSI affect adherence: results from a Delphi survey

To explore the attitudes of European physicians on adherence and how treatment modalities impact adherence in complicated forms of soft skin and skin structure infections, now referred as acute bacterial skin and skin structures infections (ABSSSI). After literature review, a questionnaire was prepared. Topics focused on (1) the importance of adherence, (2) the importance of administration regimen on adherence, (3) the importance of drug selection on adherence, (4) the importance of complexity on choice of drug for treatment, (5) the role of adherence in drug resistance, and (6) the role of adherence in administration of long-acting antibiotics (ABs). The questionnaire was administered to 323 European infectious diseases specialists, of whom 74% responded. A modified Delphi method was used to obtain the highest consensus. Results varied by countries. We found a high degree of agreement of the importance of adherence in ABSSSI treatment. Experts agreed that complexity of patient’s conditions, drug selection, drug resistance, the type of regimen, and the number of infusions impact adherence. Two items linking oral switching and adherence did not reach consensus. Adherence for ABSSSI therapies appears a crucial factor for therapeutic management and reduces the risk of AB resistance. Among new treatment opportunities, long-acting agents, with their characteristics, may represent an interesting options.

Shifting the Paradigm: The Quiet Revolution of Pediatric Procedural Sedation Practice.

On April 12, 1945, Dr Gold1 from Weill Cornell Medicine (formerly Cornell University Medical College) presented a review titled “Sedatives and Stimulants in Pediatric Practice” to the section of pediatrics. He stated that he was “disappointed indeed to learn how scant were the revelations of pediatric views on these matters” and then reviewed the primary sedatives of that time for children (barbiturates and chloral hydrate). Over the next 50 years, the vast majority of “conscious” sedation in pediatrics was still being provided with barbiturates and chloral hydrate. Because of this lack of evolution, many of the seminal articles that have been used to guide the mechanics of pediatric sedation practice emanated from 2 sources: data from sedated procedures performed with these traditional long-acting agents and data from general anesthetic cases that were extrapolated to be relevant to procedural sedation. One issue that has been largely governed by these data sets is the risk of apnea and need for prolonged observation in former term and preterm infants after a sedated procedure. The literature regarding the risk of postanesthetic apnea in infants is robust. Infants who were born prematurely carry the most notable risk, as has been described in a number of reports.2–6 Apnea has also been seen postoperatively in term infants with no previous history or known risk factors for apnea.7 In a large, multicenter review in which researchers examined risk factors for postoperative apnea in former preterm infants, postconceptual age (PCA), gestational age, and continued use of a home …

Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials.

Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long-acting dihydropyridine agent amlodipine is widely used for monotherapy and combination therapy for hypertension in clinical practice, while intermediate-acting dihydropyridine agents have shown inconsistent results in randomized clinical trials (RCTs). A meta-analysis of 18 RCTs enrolling a total of 80,483 patients with hypertension followed for a mean of 51.4 months was performed. Amlodipine therapy was associated with 25% higher risk of heart failure (relative risk [RR]: 1.25, 95% confidence interval [CI], 1.05-1.49, P = .019) but 17% lower risk of stroke (RR: 0.83, [95% CI, 0.72-0.97], P = .009) without statistically significant effect on acute myocardial infarction (AMI) compared to major alternative antihypertensive therapy (MAAT), including β-blocker, diuretic, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Intermediate-acting dihydropyridine calcium channel blocker therapy was associated with 25% higher risk of heart failure (RR: 1.25, [95% CI, 1.06-1.47], 0.005, P = .005) and 26% higher risk of AMI (RR: 1.26, [95% CI, 1.05-1.51], 0.019, P = .019) compared to MAAT. Results of the subgroup analysis suggested that the intermediate-acting dihydropyridine calcium channel blocker was associated with higher risk of heart failure (RR: 1.30, [95% CI, 1.08-1.56], P = .005) and AMI (RR: 1.50, [95% CI, 1.01-2.22], P = .043) compared to renin-angiotensin system blockers and a trend toward higher risk of AMI (RR: 1.17, [95% CI, 0.99-1.38], P = .064) compared to conventional therapy, including β-blockers and diuretics. Meta-regression analyses suggested that long-acting dihydropyridine calcium channel blocker is associated with lower risk of AMI ( B: -0.327, [95% CI, -0.530 to -0.123], P = .002) with a trend toward lower risk of stroke ( B: -0.203, [95% CI, -0.410 to 0.003] P = .054). This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate-acting dihydropyridine calcium channel blockers.

Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data.

Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist, which has been on the market in the USA since 2014. Dulaglutide has performed well in head-to-head studies against metformin, glargine, and sitagliptin, where its A1c lowering ranged from −0.78% to −1.64% over 52–104 weeks, and it consistently outperformed each of these agents. As an add-on therapy, dulaglutide provided additional A1c lowering of –1.4% to –1.44% over monotherapy with glimepiride or glargine at 24 and 28 weeks, respectively. Dulaglutide outperformed exenatide when added to a regimen of metformin with pioglitazone as well as glargine when added to a regimen of metformin with glimepiride. Dulaglutide was shown to be non-inferior to liraglutide when added to metformin. In all AWARD studies other than when compared to liraglutide, dulaglutide at full strength resulted in significantly more patients achieving their A1c goal. Recent class-wide meta-analyses indicate that the incidence of commonly experienced gastrointestinal (GI) side effects is dose dependent, and nausea and vomiting are less common in longer-acting agents such as dulaglutide, but diarrhea may be more common. Pooled data have shown no increased risk of serious side effects such as pancreatitis or neoplasm with the use of dulaglutide. Given the evidence supporting liraglutide’s cardiovascular benefits, the highly anticipated REWIND trial will have a significant impact on the future place in the therapy of dulaglutide.