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Both short-acting (SA) opioids and long-acting (LA) opioids have been used for chronic pain (defined as pain lasting >3 months). SA opioids have a duration of action ranging between 2 and 4 hours, result in rapidly fluctuating drug levels and are suitable for acute, unstable, intermittent, breakthrough, and procedure-related pain.

Chronic pain of nonmalignant nature (CNMP) is often treated with chronic opioid therapy (COT). Although many guidelines exist to help the clinician use COT in a safe and effective manner, many controversies surrounding the exact prescribing practicesremain. The purpose of these following brief case studies is to help the practicing clinician consider real patient scenarios and help further understanding of the principles outlined by the US FDA REMS document. The patient case scenarios presented in this article do not represent any one real patient. However, each case scenario is entirely plausible and has presented themselves in some likemanner to the author. These discussion and recommendations following each case scenario represent the opinion of the author alone, based on the author’s 30-year experience, a review of common published guidelines, review of the US FDA REMS paper, and a review of the literature concerning COT for CNMP. Some of the discussion points remain controversial and recommendations for therapy are based on a low level of evidence.

BACKGROUND/PURPOSE Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. METHODS From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). RESULTS There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P

Analysis of 60,000 contracts awarded by English councils between 2015–19 reveals that austerity constraints are a key predictor of councils outsourcing services to for-profit suppliers, regardless of their political control. Conservative Party-controlled councils are also more likely to contract with for-profit suppliers, although we found no link between Labour-controlled councils and not-for-profit suppliers, nor evidence that political or budgetary factors influence whether councils contract with providers based in their own region. We argue that centrally imposed funding cuts, and a belief that for-profit suppliers represent a cheaper option, could be overriding Labour Party councils' ideological preference for not-for-profit providers.

A 58-year-old Japanese man was brought to the emergency room due to disturbance of consciousness. He regained consciousness on the day of admission and started taking hospital meals, but he needed intravenous glucose administration for eight days. The total amount of glucose administration was 4,464 g. It took over three weeks for exogenous insulin to be almost undetectable. While degludec binds to albumin and exerts glucose-lowering effects for a long time, the above-mentioned period of three weeks was consistent with the half-life of albumin. Hypoglycemia induced by massive dose of insulin degludec is persistent and prominent.

To evaluate the efficacy of degludec/aspart (IDegAsp) insulin co-formulation in children and adolescents with poorly controlled type 1 diabetes (T1DM).Patients with poorly controlled T1DM on basal-bolus insulin regimes and having compliance problems related to insulin injections were switched to IDegAsp and were included. Data on hemoglobin A1c (HbA1c) levels, hypoglycemic episodes, frequency of diabetic ketoacidosis (DKA) and insulin doses were recorded at baseline and after one year of IDegAsp treatment.Fifty patients (22 girls; 44%) were started on IDegAsp. The mean±standard deviation (range) age and duration of diabetes were 12.9±3.4 (4-18) and 5.2±3.1 (1.0-13.7) years, respectively. At the end of one year, 38 patients were still on IDegAsp, whereas 12 patients had opted to resume their original treatments. In those who continued on IDegAsp, HbA1c levels did not change, but the number of self-reported mild-moderate hypoglycemic episodes decreased significantly (p0.05). In the year before switching to IDegAsp, 11 DKA attacks in 9 patients were observed, whereas this decreased to 4 DKA attacks in 4 patients after one year of IDegAsp therapy (p=0.06).IDegAsp regimen may improve clinical management in poorly controlled basal-bolus insulin regimen T1DM patients who have frequent hypoglycemia and DKA attacks, as well as in those with poor compliance with multiple injections. Although a simplified basal-bolus IDegAsp regimen is an attractive option for patients with T1DM, some may not adapt to this treatment due to the fixed IAsp dose of IDegAsp.

We compared the efficacy of the second-generation basal insulin degludec (IDeg) to that of insulin aspart via pump using continuous glucose monitoring in patients with well-controlled type 1 diabetes.In this 40-week, single-center, randomized, crossover-controlled trial, adults with well-controlled type 1 diabetes (hemoglobin A1C of7.5% [58 mmol/mol]) (N = 52) who were using an insulin pump and continuous glucose monitoring were randomized to 1 of 2 treatments for a 20-week period: a single daily injection of IDeg with bolus aspart via pump or a continuous subcutaneous insulin infusion (CSII) with aspart, followed by crossover to the other treatment. The primary endpoint was time in range (70-180 mg/dL) during the final 2 weeks of each treatment period.Fifty-two patients were randomized and completed both treatment periods. The time in range for IDeg and CSII was 71.5% and 70.9%, respectively (P = .553). The time in level 1 hypoglycemia for the 24-hour period with IDeg and CSII was 2.19% and 1.75%, respectively (P = .065). The time in level 2 hypoglycemia for the 24-hour period with IDeg and CSII was 0.355% and 0.271%, respectively (P = .212), and the nocturnal period was 0.330% and 0.381%, respectively (P = .639). The mean standard deviation of blood glucose levels for the 24-hour period for IDeg and CSII was 52.4 mg/dL and 51.0 mg/dL, respectively (P = .294). The final hemoglobin A1C level for each treatment was 7.04% (53 mmol/mol) with IDeg, and 6.95% (52 mmol/mol) with CSII (P = .288). Adverse events were similar between treatments.We observed similar glycemic control between IDeg and insulin aspart via CSII for basal insulin coverage in patients with well-controlled type 1 diabetes.

Purpose This study sought to compare the efficacy of prophylactic long-acting and standard granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia, early infections, and treatment delay in patients with newly diagnosed multiple myeloma (MM) receiving the therapeutic regimen of bortezomib, lenalidomide, and dexamethasone (VRd). Methods A prospective study with 68 consecutive patients with MM was conducted in three regional hospitals. Participants were randomly treated with the VRd regimen in combination with prophylactic long-acting G-CSF (treatment group) or prophylactic standard G-CSF (control group). The primary endpoints were the incidence rates of febrile neutropenia, early infection, and treatment delays. The secondary endpoint was clinical outcomes. Results Thirty-three patients were assigned to the treatment group, and thirty-five patients were assigned to the control group. The incidence of febrile neutropenia was 6.1% and 17.1% in the treatment and control groups, respectively (p = 0.297). However, the rates of early infection and treatment delay were markedly lower in the treatment group than in the control group (6.1% vs. 25.7% and 9.1% vs. 31.4%; p Conclusions Prophylactic administration of domestic long-acting G-CSF markedly reduced the rates of early infection and treatment delay as compared with standard G-CSF in patients newly diagnosed with MM. Notably, all early infections occurred during the first four cycles of VRd therapy. As such, it seems appropriate to administer long-acting G-CSF with the aim of primary prophylaxis of early infection in the setting of newly diagnosed MM.

Long-acting antiretroviral drugs have emerged as exciting treatment and preexposure prophylaxis (PrEP) options for people with HIV and at risk of HIV. Long-acting regimens may improve dosing convenience, tolerability and cost compared with current daily-based oral therapy. They can also circumvent stigma associated with oral therapy for both treatment and PrEP, thereby improving adherence and outcomes. Yet, multiple challenges remain, many specific to low-income and middle-income countries (LMICs), where the epidemic is most concentrated and HIV prevention and treatment options are limited. To optimize the use of long-acting formulations, key outstanding questions must be addressed. Uncertain costing, scale-up manufacturing, complex delivery systems and implementation challenges are potential barriers when considering the scalability of long-acting ARVs for global use.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

The aim of the studies was to evaluate the safety, tolerability, and efficacy of tafolecimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, in Chinese healthy volunteers and patients with hypercholesterolemia. Fifty-eight healthy volunteers (phase 1a) were randomized to receive a single dose of 25, 75, 150, 300, 450, or 600 mg tafolecimab subcutaneously, 75 or 450 mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140 mg tafolecimab every 2 weeks, 300 or 420 mg every 4 weeks, or 450 or 600 mg every 6 weeks subcutaneously or placebo for 12 weeks. Tafolecimab was well tolerated. Adverse events in both studies were either mild or moderate. In the phase 1a study, a single dose of tafolecimab reduced low-density lipoprotein-cholesterol (LDL-C) levels up to 72% in healthy volunteers. In the phase 1b study, tafolecimab reduced LDL-C levels up to 71.6% and by more than 50% consistently to week 12 for all tafolecimab dose regimens. Tafolecimab is a safe PCSK9 monoclonal antibody with significant and potential long-acting LDL-C–lowering effect. (Single Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Healthy Subjects; NCT03366688 ) (Multiple Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Chinese Patients With Hypercholesterolemia; NCT03815812 )

Direct-acting oral anticoagulants (DOACs) vary in bioavailability and sites of absorption in the gastrointestinal tract (GIT). Data on DOAC use after major GIT surgery are limited. The aim of this case series was to report the impact of surgical resection or bypass of the GIT on rivaroxaban and apixaban peak plasma concentrations. This was a case series of patients who received rivaroxaban or apixaban after GIT surgery, during the period of July 1, 2019, to December 31, 2020. Peak plasma concentrations of rivaroxaban and apixaban were assessed for the expected concentrations. Of the 27 assessed patients, 18 (66.7%) received rivaroxaban, and 9 (33.3%) received apixaban. After rivaroxaban therapy, 4 of 5 patients (80%) who underwent gastrectomy, and 3 of 3 patients (100%) who underwent duodenum and proximal jejunum exclusion had peak plasma concentrations of rivaroxaban lower than the effective range, whereas 11 of 11 patients (100%) who underwent distal bowel or ileostomy had peak rivaroxaban plasma within the effective range. After apixaban therapy, 5 of 6 patients (83.3%) who underwent total or partial gastrectomy achieved effective peak concentrations. All the patients who underwent proximal and distal bowel resection or bypass had peak concentrations of apixaban within the effective range. In conclusion, surgical resection or bypass of the upper GIT could affect DOAC absorption and subsequently peak plasma concentrations. This effect was more observed among rivaroxaban recipients. An injectable anticoagulant or vitamin K antagonist may be preferred if DOAC concentrations cannot be measured after GIT surgery.

BACKGROUND Insufficient and contradictory data are available about the relation between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV). AIM To analyze differences in basic clinical, radiological, and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure. METHODS This multicenter case-control study included 497 patients with chronic HCV-related HCC, allocated into one of two groups according to their history of antiviral treatment for their HCV. RESULTS Group I included 151 HCC patients with a history of DAAs, while 346 patients who had never been treated with DAAs were assigned to group II. A significant difference was observed between both groups regarding basic assessment scores (Child, MELD, and BCLC), which tended to have more advanced liver disease and HCC stage upon diagnosis in group I. However, serum albumin was significantly affected, and serum α-fetoprotein was significantly higher in group II (P < 0.001). In addition, group I showed significant HCC multicentricity than group II, while the incidence of portal vein thrombosis was significantly higher in group I (P < 0.001). CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment; however, HCC behavior is more aggressive in DAA-treated patients.

Long-distance transport of caribou (Rangifer tarandus) can result in morbidities and mortalities. This case report describes the use of a long-acting tranquilizer, zuclopenthixol acetate (ZA) and live video monitoring (LVM) to transport caribou over 2300 kilometers. Two groups of captive caribou were transported from Fort St. John, British Columbia to Dryden, Ontario (n=14; 28.5 h transport) and Anchorage, Alaska (n=11; 32 h transport). The day prior to transport, caribou were administered ZA at 1 mg/kg via deep intramuscular (IM) injection. Digital video cameras allowed for live observation of caribou during transport. Still images of videos from each compartment in the Ontario transport were analyzed for percentage (%) lying versus standing over three time periods (Day 1, Night, and Day 2). Overall, caribou spent 57% of the transport lying down, with the highest percentage occurring at night (73%). As group size and animal density decreased there was a trend for caribou to spend more time lying down. Three animals developed extrapyramidal effects to the ZA and were effectively treated with midazolam at 0.2 mg/kg IM. There were no significant visible injuries or mortalities during or up to 6 weeks post-transport. Zuclopenthixol acetate and LVM were used to successfully transport caribou over long distances and should be considered in future translocations to improve animal welfare during transport.

Background. Long-acting injectable (LAI) antipsychotics are used as a monotherapy in patients with schizophrenia. However, the combination of LAI and oral antipsychotics is commonly used in clinical practice, despite there being very limited studies investigating the efficacy and safety of this combination compared with LAI antipsychotic monotherapy. Objective. To study the efficacy and safety of LAI antipsychotic monotherapy compared with the combination of LAI and oral antipsychotics in patients with schizophrenia. Methods. This study was a retrospective cohort study, which classified eligible patients into two groups: the LAI antipsychotic monotherapy group and the combination of LAI and oral antipsychotic group. The primary outcome was hospitalization between groups. The duration of the study was 2 years. Results. In total, 86 patients completed the study and were analysed (LAI antipsychotic monotherapy group: n = 25 ; combination of LAI and oral antipsychotic group: n = 61 ). There was no significant difference in hospitalization between the two groups ( P = 1.000 ). For other outcomes, there were also no significant differences in both all-cause discontinuation ( P = 0.667 ) and adverse drug reactions ( P = 0.732 ) between the two groups. Conclusion. The efficacy and safety of LAI antipsychotic monotherapy appeared similar to the combination of LAI and oral antipsychotics in patients with schizophrenia. Therefore, the combination of LAI and oral antipsychotics, which is commonly used in clinical practice, may not be necessary.

Purpose of review Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). This review focuses on phase 3 clinical trial results and implementation considerations for these long-acting ART and PrEP strategies. Recent findings Long-acting CAB and RPV administered every 4 weeks demonstrated noninferiority to oral ART through week 96 in both the ATLAS and FLAIR studies, whereas ATLAS-2M found similar efficacy through 96 weeks when the long-acting injectable ART was administered every 8 weeks instead of every 4 weeks. For prevention, two phase 3 trials were stopped early due to fewer incident HIV infections in participants receiving long-acting CAB every 8 weeks compared with daily oral tenofovir disoproxil fumarate–emtricitabine for PrEP. The long-acting therapies were well tolerated across all clinical trials. Summary Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. Implementation challenges persist, and data are urgently needed in populations who may benefit most from long-acting therapy, including adolescents, pregnant individuals, and those with barriers to medication adherence.

Introduction Insulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting. Methods Multicentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician’s discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs [primary endpoint]), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS). Results Overall, 1321 patients were included (SAS, n = 1321; EAS, n = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate [95% confidence interval (CI)] of 16.2 events/100 patient-years of exposure (PYE) [14.0; 18.4]. By preferred term, ‘hypoglycaemia’ was the most frequent AE (45 events in 31 patients [2.3%]; rate [95% CI] 3.6 events/100 PYE [2.5; 4.6]). Serious AEs occurred in 4.2% of patients (rate [95% CI] 5.7 events/100 PYE [4.4; 7.0]), and ADRs in 3.1% (rate [95% CI] 4.6 reactions/100 PYE [3.4; 5.8]). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate [95% CI] 0.5 events/100 PYE [0.1; 0.9]). Change from baseline to 1 year was − 0.51% and − 32.1 mg/dL for HbA1c and FPG, respectively (P

Objective: The objective of this study was to analyze the real-world prevalence of long-acting injectable (LAI) antipsychotic use and determine when LAIs are being used in sequencing of antipsychotic medications among Canadian patients with schizophrenia. Methods: This was a retrospective, longitudinal cohort study using Canadian pharmacy prescription data between August 2005 and June 2017. Patients with inferred schizophrenia spectrum disorder were indexed on the date of their first antipsychotic prescription and analyzed for minimum 12 months to track lines of antipsychotic therapy and LAI utilization. Results: A total of 16,300 patients were identified for analysis. 48.2% and 46.0% of index antipsychotic prescriptions were prescribed by a general practitioner/family medicine doctor and psychiatrist, respectively. 1,062 (6.5%) patients used an LAI during the study period. Of those patients, 789 used an LAI within two years of index (74.3% of LAI users; 4.8% of all patients). The majority of LAI use (62.0%) occurred in the third line of therapy or later. 65.0% of patients had tried at least two therapy lines, and most patients reported gaps of six months to one year between treatment lines. Conclusion: Despite their potential to reduce relapse in schizophrenia by improving treatment adherence, this study shows LAIs continue to be under-utilized in Canada. When used, LAIs are positioned late in sequencing of antipsychotic medications, often not initiated until years after diagnosis. Continued preference for oral APs with poor adherence may be negatively impacting prognosis and exacerbating burden of schizophrenia. Efforts should be invested to understand barriers to LAI uptake and advocate for earlier, widespread use of LAIs.

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (рConclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

Australia was one of the first countries with unrestricted access to government subsidized direct-acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real-world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow-up. Real-world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH-C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention-to-treat (ITT) and per-protocol (PP) analyses. Within REACH-C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43-0.72), cirrhosis (aOR 0.52, 95% CI 0.41-0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46-0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28-0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow-up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44-2.11; IDU + OAT: aOR 1.39, 95% CI 1.11-1.74; OAT only, aOR 1.36; 95% CI 1.13-1.68) and age (aOR 0.97, 95% CI 0.97-0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow-up presents a real-world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow-up.

Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤...

Aims/Introduction To evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real‐world clinical setting. Materials and Methods A total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain. Results HbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately −0.3% and −0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors. Conclusions The current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction., Insulin degludec and insulin glargine 300 U/mL showed similar values of reduction in glycated hemoglobin with body mass index almost unchanged 6 months after switching from other basal insulins in both type 1 and type 2 diabetes patients. Switching to insulin degludec was significantly associated with a reduction of basal and total insulin doses in both type 1 and type 2 diabetes patients.

Background: Spinal anesthesia is a reliable and safe technique for infraumbilical surgeries. Nevertheless, some of its characteristics may limit its use for day care surgery. Use of long-acting anesthetic drugs like bupivacaine in spinal anesthesia may lead to side effects such as delayed ambulation and risk of urinary retention. Chloroprocaine is an amino-ester local anesthetic with a very short half-life now being extensively evaluated in volunteer studies and clinical practice with a favorable safety profile and efficacy, suggesting that it may be a suitable alternative to long-acting local anesthetics like bupivacaine in day care surgeries. Aims and Objective: This study aims at evaluating the duration and efficacy of chloroprocaine in spinal anesthesia for infraumbilical surgeries. The primary outcome of the study was to evaluate the duration and efficacy of chloroprocaine 1% in spinal anesthesia for infraumbilical surgeries and the secondary outcome was to find out the incidence of adverse effects if any. Materials and Methods: In this randomized single-blinded clinical evaluation, after institutional ethical committee approval, 30 adult patients (18–70 years, ASA physical Status I-III, BMI < 36 kg/m2) scheduled for infraumbilical surgeries received chloroprocaine 40 mg intrathecally. Patients were evaluated for onset and regression of sensory and motor blockade, peak level of sensory blockade, and time of ambulation postoperatively. Results: The average duration of the surgeries was 46.87±15.24 min. Anesthesia was sufficient for the planned surgery. Only three patients required sedation intraoperatively. The median peak sensory block height was T8. The mean time for peak height sensory block was 6.6±1.673 min and complete motor block was 2±1.05 min. Mean time for complete sensory block regression was 95.37±20.79 min and complete motor block regression was 81.43±20.33 min. Four patients required inj. atropine following bradycardia and three patients required vasopressors following hypotension. Conclusion: Spinal anesthesia with chloroprocaine provides reliable sensory and motor block for short duration infraumbilical surgeries with fewer intraoperative and post-operative complications.

OBJECTIVE: To provide an overview of the existing international and Chinese evidence regarding dual bronchodilator inhalation therapy and to make recommendations for the further improvement of chronic obstructive pulmonary disease (COPD) management in clinical practice in China. BACKGROUND: COPD is a progressive lung disease that is characterized by persistent airflow limitation and is a major contributor to the disease burden in China. Symptoms in Chinese patients are relatively more severe. Currently, many Chinese COPD patients are undertreated. Dual bronchodilator therapy consisting of a long-acting muscarinic antagonist (LAMA) and a long-acting β agonist (LABA) is considered a good choice for COPD patients due to the increased bronchodilation without an increase in adverse events; these combinations can fill in the gap in currently available COPD treatments and provide new pharmacotherapy options for Chinese patients. LAMA/LABA fixed-dose combinations (FDCs) have become more important in clinical practice and guidelines in China regarding their therapeutic effects and safety. METHODS: Clinical trials on LAMA/LABA in COPD were retrieved in ClinicalTrials.gov, while important COPD guidelines published in English or Chinese were found in PubMed and Wanfang Database. CONCLUSIONS: We recommend the adoption of a clinical pathway in China that includes an assessment and management algorithm that considers the clinical characteristics in China and classifies the phenotypic characteristics of COPD according to a suitable system. Based on the current information, we can conclude that LAMA/LABA FDCs are a suitable and economically viable choice to reduce symptoms and improve the quality of life (QoL) of patients.

Aim: In this study, we sought to determine clinical outcomes at 1 year for patients prescribed penfluridol in an inner London National Health Service Trust. Using noninterventional data, we describe the use, effectiveness and safety of this treatment modality. Results: We retrospectively followed up 17 patients prescribed penfluridol as part of routine clinical practice. All patients took penfluridol once weekly. Of these patients, 12 (70.6%) were considered treatment resistant. The average duration of illness for this cohort was 10 years (SD = 6.7). At 1 year, nine (53%) patients remained on treatment. Median survival time was not reached at 1-year follow-up; mean time on penfluridol was 251 days (95% confidence interval (CI), 184–318). The mean number of admissions to hospital in the year following penfluridol initiation was 0.6 compared with 0.8, 1 year before initiation ( p = 0.465). The median number of bed days 1 year before penfluridol initiation was 24, whereas in the year following penfluridol initiation, it was 0 ( p = 0.514). Clinical Implications: Although penfluridol is unlicensed in the United Kingdom, limited data suggest that this long-acting oral therapy has the potential to be used safely and effectively for the treatment of psychotic disorders. However, more data are required to establish the place of penfluridol and other potential long-acting oral antipsychotic formulations in the treatment of psychotic disorders.

Direct-acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved liver function of HCV patients. The risk of hepatocellular carcinoma (HCC) occurrence following HCV eradication has been previously reported, but HCC may have been missed following imaging diagnosis before DAA administration in previous studies. Therefore, the present study aimed to identify definite predictors of HCC occurrence ≥1 year after DAA treatment. Among 956 patients receiving DAAs for HCV infection, 567 patients who achieved sustained virologic response with no history of HCC treatment were enrolled in this study between September 2014 and July 2021. The incidence of HCC in HCV-infected patients ≥1 year following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinical characteristics and blood test results. In the present study, 25 patients developed HCC. The incidence of HCC was 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from the end of treatment with DAAs. Multivariate logistic analysis revealed serum α-fetoprotein level at end of treatment (EOT-AFP) >3.8 ng/ml ≥1 year following treatment with DAAs (HR, 9.7; p

All over the world hepatitis C is a global medical and social health problem, along with HIV infection, tuberculosis, hepatitis B, etc. According to the latest WHO estimates, the overall number of patients with chronic hepatitis C (CHC) in 2015 amounted to 71 million people (1 % of the world’s population). In Russia there are 5 million such patients. The largest number of people registered with CHC diagnosed in the Russian Federation is registered and lives in the Volga Federal District – 23.3 % (143,477 people). The incidence in the city of Ulyanovsk is very high (81.7 per 100 thousand of the population), and tends to grow steadily. The aim of this paper is to determine the effectiveness of 3D therapy in real clinical practice. Materials and Methods. Clinical charts of 151 patients with hepatitis C who underwent 8- and 12-week 3D and 3D+ ribavirin therapy (3 people) were analyzed. After therapy, the biochemical and virological responses were studied. The density of the liver tissue was determined on the FibriScanCompact 530 (Echosens, France). Results. There was a 100 % rate of sustained virological response to 8- and 12-week 3D therapy in complex groups of patients (extrahepatic manifestations, severe comorbid pathology, patients without previous responce to therapy). Triple therapy (Vikeira Pak) reduced the need for retreatment. Evaluation of interactions of direct antiviral drugs (3D scheme) in combination with ribavirin and without it was carried out with the most frequently prescribed drugs in the cohort of our patients. The 3D therapy regimen had a good safety profile: none of the patients cancelled treatment due to adverse events. Key words: chronic viral hepatitis C, 3D therapy, ombitasvir + paritaprevir + ritonavir, sustained virological response, genotype 1. Гепатит С является глобальной медико-социальной проблемой здравоохранения во всем мире наряду с такими заболеваниями, как ВИЧ-инфекция, туберкулез, гепатит В и ряд других инфекционных болезней. Согласно последним оценкам ВОЗ число больных хроническим гепатитом С (ХГС) в мире в 2015 г. составило 71 млн чел. (1 % населения Земли), из них 5 млн проживает в России. Наибольшее число лиц, состоящих на учете с диагнозом ХГС в РФ, зарегистрировано и проживает в Приволжском федеральном округе – 23,3 % (143 477 чел.). Заболеваемость в г. Ульяновске очень высока, составляет 81,7 на 100 тыс. населения и имеет тенденцию к неуклонному росту. Цель работы – определение эффективности 3D-терапии в реальной клинической практике. Материалы и методы. Проанализированы истории болезни 151 пациента с диагнозом «гепатит С». Все больные прошли курсы терапии 3D и 3D+рибавирин (3 чел.) в режиме 8 и 12 нед. Изучены биохимический, вирусологический ответы, после проведенного курса терапии определена плотность печеночной ткани на аппарате FibriScanCompact 530 (Echosens, Франция). Результаты. Доказана 100 % частота устойчивого вирусологического ответа на 8- и 12-недельные курсы 3D-терапии у сложных групп пациентов (с внепеченочными проявлениями, с тяжелой коморбидной патологией, у пациентов, ранее не отвечавших на терапию). Выбор трехкомпонентной терапии препаратом «Викейра Пак» обоснован возможностью снижения потребности в повторных курсах терапии. Оценка лекарственных взаимодействий препаратов прямого противовирусного действия схемы 3D в сочетании с рибавирином и без него производилась с наиболее часто назначаемыми препаратами в когорте наблюдаемых нами пациентов. Схема 3D-терапии имеет хороший профиль безопасности, ни один из пациентов не прекратил лечение в связи с нежелательными явлениями. Ключевые слова: хронический вирусный гепатит С, 3D-терапия, омбитасфир+паритапревир+ритонавир, устойчивый вирусологический ответ, генотип 1.

This paper reviews the literature examining antipsychotic prescription disparities between white people and black people. Despite literature documenting racial discrepancies in diagnosis, there have been limited studies examining disparities in antipsychotic prescription between white people and black people. Studies have demonstrated that black people are more likely to receive first generation antipsychotics, higher antipsychotic doses, and long acting injectables, but less likely to receive clozapine. Much of this work was done in the early 2000s. Future research directions include investigation into why these disparities exist. Literature examining these disparities has focused on genetic and sociological factors; however, the impact of prescriber bias and structural racism remains underexplored. Until the research proceeds, future clinical directions should include empowering patients, families, and clinicians to question practices that may exacerbate these known disparities.

Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). Design: A Phase 2b, multicenter, open-label, rollover study. Methods: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. Results: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. Conclusion: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.

PURPOSE IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. METHODS ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of

BACKGROUND Several factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct-acting anti-virals (DAAs). AIMS To develop a prediction model for HCC occurrence after DAA-mediated SVR and validate its usefulness. METHODS We analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients). RESULTS In the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2 , P = 0.024), baseline fibrosis-4 (FIB-4) index (≥3.25, P = 0.001), albumin level at SVR (

Clinical trials conducted in various countries indicate that the use of epoetin alfa in patients with nephrogenic anemia in chronic kidney disease can increase the effectiveness of treatment, reduce the incidence of cardiovascular and infectious complications, and reduce mortality in patients with chronic kidney disease.The aim of the article was to conduct a comparative clinical and economic assessment of the treatment costs of nephrogenic anemia in adult dialysis patients with recombinant human erythropoietins: epoetin alfa, darbepoetin and long-acting methoxy polyethylene glycol – epoetin beta.Materials and methods. The study took into account direct medical costs of nephrogenic anemia pharmacotherapy on the basis of 1 year maintenance therapy according to the following scheme: epoetin alfa – 3 times per week, darbepoetin alfa – once per week, methoxy polyethylene glycol – epoetin beta – once per 2 or 4 weeks. A “costs minimization” analysis was performed for equivalent maintenance epoetins doses for intravenous and subcutaneous administrations. Epoetin alpha equivalents were calculated for an average patient weighing 75 kg by converting a weekly dose of short-acting epoetin (7500 IU) into equivalent doses using dose conversion factors.Results. In the hypothetical cohort of patients under study, epoetin alfa, darbepoetin alfa, and methoxy polyethylene glycol – epoetin beta not differ in effectiveness in achieving target Hb values and in safety. With the equal effectiveness of the investigated drugs, in the studied patients, intravenous epoetin alfa can be less expensive drug therapy relative to the equivalent doses obtained by the calculation: darbepoetin by 14–24% and methoxy polyethylene glycol – epoetin beta by 4–30%. The change-over of patients to the subcutaneous administration makes it possible to decline a weekly dose of epoetin alfa by 20–30% by reducing the frequency of taking the drug to twice a week, and to reduce the cost of drug therapy by a third.Conclusion. Intravenous and subcutaneous administrations of epoetin alfa 2500 IU may be a more economical drug therapy in comparison with the equivalent doses of darbepoetin and methoxy polyethylene glycol – epoetin beta.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (

Study Objective To assess whether improving providers’ education by video training using a mobile phone could affect providers’ knowledge and attitude toward long-acting reversible contraceptives (LARCs), and thus further affect adolescents’ and young nulliparous women's decisions to use LARCs. Design, Setting, Participants, Intervention, and Main Outcome Measures This prospective case-control study was performed between 2019 and 2020. A total of 40 healthcare providers participated, of which 20 received “LARC First” video training, whereas the other 20 served as the control group and received no training. Surveys were conducted of 244 adolescents and young women who were consulted by these 2 groups of healthcare providers before abortion surgery. The data were used to analyze the relationship between providers’ knowledge scores and the percentage of women who received counseling on LARCs decided to use LARCs, and what percentage continued to do so 12 months after surgery. Results Providers from the study group scored higher in LARC knowledge than the control group. Compared to the control group, women in the study group reported receiving more counseling on LARCs (81.4% vs 7.9%) and more often chose to use LARCs (24.6% vs 2.4%). Twelve months later, there was no significant difference in contraceptive continuation between study and control groups, but study group participants were more likely to be using LARCs (P Conclusion Video training for providers improved both their knowledge and willingness to recommend LARCs and increased the probability of adolescent and young nulliparous women using these methods to reduce unintended pregnancy.

Objectives Preparation of injectable anticancer drugs in hospital pharmacies, in particular of cytotoxics, is a high-risk activity. We used Preliminary Risk Analysis (PRA) to analyse the risks in the different steps of our anticancer drug circuit, including the preparation step (PRA1). Then, to prepare an important change in management of the circuit with the software Chimio® (pooling of three databases for subcontracting), we repeated the analysis of preparation step (PRA2). PRA is known to be time and resource consuming. To overcome this, we developed a strict organisational framework to perform the analysis within a reasonable amount of time. We present the PRA method including its practical implementation, and its application to the anticancer drug preparation process, before and after pooling of Chimio® databases. Methods PRA has two main stages, PRA “system” and PRA “scenario”. A multidisciplinary working group is created for the entire PRA process. PRA “system” is an exploratory and qualitative stage. PRA “scenario” requires the creation of risk assessment tools and decision tools before actually developing, analysing and treating scenarios, with risk reduction actions structured in an action plan. For PRA2 we used the same working group, assessment and decision tools as for PRA1 and we only analysed dangerous situations (DS) that appeared or changed towards more risk, requiring a new action plan. The different PRA only required four 2 h meetings thanks to the investment of a coordinator who is expert in the method. Results In PRA1, the riskiest phase was production while it was the verification and delivery of the finished product in PRA2. The risks were mainly related to management, human and technical dangers in PRA1. Human danger was found to be the main danger in PRA2, followed by organisational danger. Among the 264 scenarios described in PRA1, six of criticality 3 and 69 of criticality 2 have been associated with risk reduction actions. These actions mainly involved managing the risk of human error, with the control system Drugcam® and the standardisation of the pharmaceutical assistants’ training program. In PRA2, 11 scenarios were analysed, including three of criticality 3 and 4 of criticality 2 for which risk reduction measures were taken. Conclusions PRA allowed us to perform an in depth analysis of the highly specific and technical process of anticancer drug preparation. Human danger was one of the most important dangers identified, and it should always be taken into consideration, whatever the measures taken to prevent it. PRA2 was extremely useful to plan the organisation that would result from the new Chimio® database, while involving the team and winning its commitment. It allowed an exhaustive and structured anticipation of this major change. Practical aspects of PRA method implementation we have adopted facilitate its application and can help to deploy it on many areas in our hospitals. Indeed, besides an exhaustive analysis of the risks, this approach promotes collaboration, develops a quality culture and is an excellent tool for team and project management, as well as communication.

Schizophrenia is a serious mental illness that requires continuous and effective long-term management to reduce symptoms, improve quality of life, and prevent relapse. Oral antipsychotic medications have proven efficacy for many patients taking these medications; however, a considerable number of patients continue to experience ongoing symptoms and relapse, often due to lack of adherence. The advent of long-acting injectable (LAI) formulations of antipsychotic medications provided an opportunity to improve treatment adherence and overall patient outcomes. Despite data to support LAI efficacy, safety, and improved adherence over oral formulations, there are several misconceptions about and barriers to LAI implementation within a standard of care for patients with schizophrenia. Areas of resistance around LAIs include (1) doubts regarding their benefits outside of improved adherence, (2) questions regarding their prescribing to a broader population of patients with schizophrenia, (3) when to initiate LAIs, (4) concerns regarding the safety of LAIs in comparison with oral medication, and (5) the most effective ways to educate healthcare providers, patients, and caretakers to enable appropriate LAI consideration and acceptance. Here, we discuss these key controversies associated with LAIs and provide supportive evidence to facilitate LAI use in a manner that is constructive to the clinician–patient relationship and successful treatment., Plain Language Summary Schizophrenia is a mental condition that affects how a person acts, thinks, sees, and interprets their surroundings and expresses how they feel. Relapse can lead to hospitalization and other poor outcomes. Almost half of patients with schizophrenia tend to start and stop treatment, which can cause more relapses and make symptoms worse over time. Using antipsychotic drugs long term can reduce impairing illness symptoms and improve patient quality of life. Consistent use of antipsychotic drugs can help prevent relapse. Available antipsychotic drugs can be taken by mouth (oral) or by an injection. Oral drugs have to be taken every day, whereas long-acting injections (LAIs) of antipsychotic drugs can be given less often, such as every 2 weeks, monthly, and up to once every 3 months. In the past, LAIs were used only when oral antipsychotic drugs did not work, which was usually because patients did not take them every day. However, LAIs also work as an early treatment, which can be better for the patient. Patients taking LAIs skip fewer doses and so may have fewer relapses and hospitalizations. Because LAIs have to be given at the clinic, patients get more regular medical care and tend to keep taking their medicine for longer. Most LAI side effects are similar to those of oral antipsychotic drugs. Despite this, some clinicians hesitate to prescribe LAIs. More education for clinicians and patients about LAIs could increase interest and use. Recovery and relapse prevention are the main treatment goals for patients and their care team, and LAIs can improve both.

Bronchial asthma remains one of the most common chronic respiratory diseases. The apparent heterogeneity of BA underlies the concept of phenotype-specific or patient-centered therapy. However, in real clinical practice, BA continues to be regarded as a rather homogeneous pathological condition and its treatment in the vast majority of cases retains an empirical approach, the basis of which are inhaled glucocorticosteroids, usually in combination with long-acting beta2-agonists. Since this group of drugs is very representative, the physician is faced with the question of choosing the optimal drug. The basis of evidence-based medicine is a hierarchical classification, where systematic reviews, meta-analyses, and randomized clinical trials are considered the highest level of evidence. Because randomized clinical trials are conducted in carefully selected highly selected patient populations, they have little relevance to patients encountered in everyday clinical practice. In contrast, pragmatic randomized clinical trials assess the clinical efficacy of the investigational agent in a large, unselected population in which patients with comorbidities are included. In this context, the Salford Lung Study (SLS) is of particular interest. It was conducted before the registration of a new combination drug containing the modern ICS fluticasone furoate and the long-acting beta2-agonist vilanterol. The SLS results indicated not only that the use of fluticasone furoate with vilanterol provides better control of BA compared to continued "conventional therapy" (ICS ± LABAs) in symptomatic patients, but also leads to a consistent improvement in the surrogate parameters of quality of life.

AIMS: Limited data exists about the use of insulin degludec in the hospital. This multicentre, non-inferiority, open-label, prospective randomised trial compared the safety and efficacy of insulin degludec-U100 and glargine-U100 for the management of hospitalized patients with type 2 diabetes. METHODS: A total of 180 general medicine and surgery patients with an admission blood glucose (BG) between 7·8 – 22·2 mmol/L, treated with oral agents or insulin prior to hospitalization were randomly allocated (1:1) to a basal bolus regimen using degludec (n=92) or glargine (n=88), as basal and aspart before meals. Insulin dose was adjusted daily to a target BG between 3·9 – 10·0 mmol/L. The primary end point was difference in the mean hospital daily BG between groups. RESULTS: Overall, the randomization BG was 12·2 ± 2·9 mmol/L and HbA1c 84 mmol/mol (9·8±2·0%). There were no differences in mean daily BG (10·0±2·1 vs. 10·0±2·5 mmol/L, p=0·9), proportion of BG in target range (54·5± 29% vs. 55·3 ± 28%, p=0·85), basal insulin (29·6 ± 13 vs 30·4 ± 18 units/day, p=0·85), length of stay (median (IQR): 6·7 (4·7–10·5) vs. 7·5 (4·7–11·6) days, p=0·61), hospital complications (23% vs. 23%, p=0·95) between treatment groups. There were no differences in the proportion of patients with BG

The effective treatment of asthma is important in terms of improving the quality of life and decreasing the number of hospital admissions due to acute exacerbations. Parasymphatic activity is increased in patients with asthma. This is one of most important part of airway obstruction which has a great potential for reversibility. The evidence about the synergic interaction between inhaled corticosteroids (ICS), long acting beta-2 agonists (LABA), and long acting muscarinic antagonists (LAMA) encourages the use of LAMA in asthma. Tiotropium treatment was found to be successful in patients with recurrent exacerbations in whom asthma was uncontrolled despite treatment with other add on treatments that were recommended at GINA step 4. These findings triggered several clinical studies on fixed dose ICS/LABA/LAMA for asthma treatment. Three studies that have been published recently showed that fixed dose ICS/LABA/LAMA improved the lung functions and decreased the exacerbation rate without increasing the dose of ICS or LABA in asthma. In this review, the mechanisms of action of LAMA in asthma were summarized and possible role of fixed dose ICS/LABA/ LAMA in asthma treatment was discussed under the light of current literature.

A major shift in the U.S. contraceptive method mix has been the recent growth in the use of long-acting reversible contraceptives (LARCs)—intrauterine devices and implants. Quantitative research into LARC’s impacts until now has focused on evaluating their efficacy in reducing unintended pregnancies. The next question, of whether births after discontinuing LARC use are then more likely to result from an intended pregnancy, has received almost no attention. We analyzed data from 2984 women who reported a live birth in the 3–4 years prior to survey interview for the 2006–2015 cycles of the National Survey of Family Growth. We compared the proportion of births intended by last contraceptive method used. To capture contraceptive failure versus stopping contraceptive use to become pregnant, we estimated logistic regressions alternately not controlling for, and controlling for, use of contraception in the month of conception. We found that four in five births following LARC use were reported to result from an intended pregnancy, compared to only three in five births following use of a moderately-effective or less-effective method. After controlling for use of contraception in the month of conception and for socio-demographic characteristics, women whose last-used method was a LARC had twice the odds of reporting that the pregnancy was intended relative to women whose last-used method was either a moderately-effective method or a less-effective method. We conclude that U.S. women’s LARC use has the potential to increase the fraction of subsequent births from intended pregnancies, and in doing so promote their reproductive autonomy.

Background/Objectives. Liver fibrosis is the inevitable end result of chronic hepatitis C (HCV) infection and is responsible for almost all liver-related complications. After the big advancement in therapeutics of HCV, liver fibrosis would expectedly improve after viral clearance. Many studies showed significant improvement of liver fibrosis shortly after successful treatment with direct acting antiviral agents (DAAs); however, the long-term changes have been scarcely addressed in the literature. We aimed to trace dynamical changes in liver stiffness 1, 3, and 5 years after HCV eradication. Methods. Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. Results. The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa p < 0.0001 at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa p < 0.0001 . The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. Conclusions. There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0–F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3–F4) take a longer time to regress to lower fibrosis stages.

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders (OUDs). Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs: (1) CAM 2038 (Buvidal) for subcutaneous weekly and monthly application; (2) RBP-6000 (Sublocade™) as a monthly depot formulation; and (3) A six-month buprenorphine implant [Probuphine™]. The pharmacology, clinical efficacy and prospects of these medications are discussed.

To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database.A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience.Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Objective To compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments. Methods Retrospective analysis of anonymized, propensity score–matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020. Results Data were analyzed from propensity score–matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (−27.84%; 95% confidence interval [CI] −29.71 to −25.96; P Conclusion Within study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.

Introduction Type 1 diabetes is characterized by insulin deficiency and requires near-physiological insulin replacement. In most patients, this is accomplished by basal bolus therapy consisting of a long-acting basal insulin administered once or twice daily and short-acting insulin with main meals. Several long-acting insulin analogs have been developed to optimize basal insulin therapy. Areas covered This paper reviews the design of - and data from - randomized controlled trials (RCTs) to assess glucose lowering efficacy and safety of long-acting insulin analogs for the treatment of type 1 diabetes. Expert opinion Due to the non-inferiority treat-to-target design of insulin, RCTs treatment differences primarily appear as differences in hypoglycemia risk. Data suggest that the first generation long-acting insulin analogs insulin glargine U100 and insulin detemir have a similar glucose lowering efficacy compared to NPH insulin but a lower risk of hypoglycemia, particularly during nighttime. The newer analogs insulin glargine U300 and insulin degludec provide non-inferior efficacy, although insulin glargine U300 is less potent unit-to-unit. Insulin degludec reduces hypoglycemia risk compared to insulin glargine U100. Future studies should explore the potential for further improvement of treatment results in type 1 diabetes by a structured approach to personalization of basal insulin therapy.

Long-acting injectable antipsychotics (LAIs) increase drug compliance and offer a reliable treatment option with stable pharmacokinetics. The aim of our study is to examine the rate and predictors of LAIs' prescription at discharge in inpatients with schizophrenia and other psychotic disorders. This retrospective study included 400 inpatients. Sociodemographic and clinical characteristics of the patients, the treatments applied in the past and prescribed at discharge were obtained from the hospitalization files. We compared these characteristics of those who were given LAI treatment at discharge to the patients who were given oral treatments. Thirty-nine percent of the patients were prescribed a LAI at discharge. Duration of illness was longer, and number of previous hospitalizations was higher in the LAI group. Nonadherence to the antipsychotics before the hospitalization, the previous history of LAI use, lack of insight at the admission and no previous antidepressant use were found as independent contributors to LAI prescription as the treatment of discharge in logistic regression analysis. Our study showed that LAIs are used at a high rate in our clinic; however, they are still initiated at a later stage, mostly in chronic patients with a lack of insight and compliance at admission.

International schizophrenia guidelines endorse seeking the patient's preference for guiding antipsychotic therapy. There exists a small niche of patients who prefer, or are required to use, long-acting injectable antipsychotic medications due to the adherence benefit. However, they may not be able to achieve adequate symptom reduction prior to experiencing treatment-limiting adverse effects from a single agent. Here, we present a patient case prescribed concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate due to patient preference in the setting of a history of nonadherence to oral medications, treatment-limiting adverse effects to long-acting injectable paliperidone, and failure to achieve adequate symptom reduction with long-acting injectable aripiprazole monotherapy.