Dosing Pattern Research Articles

Antiviral activity of esculin against white spot syndrome virus: A new starting point for prevention and control of white spot disease outbreaks in shrimp seedling culture.

White spot syndrome virus (WSSV) is a pathogenic and threatening virus in shrimp culture for which there is no effective control strategy. Finding antiviral lead compounds for the development of anti-WSSV drugs is urgent and necessary; in this study, esculin from 12 monomeric compounds exhibited an excellent anti-WSSV activity. The results showed that esculin increased the survival rate of WSSV-infected shrimps by 59% and reduced the virus copy number in vivo over 90% at 100μM. In the pre-treatment and post-treatment experiments, esculin could prevent and treat WSSV infection. Compared with the control group, the virus copy number decreased by 30% after 6h of esculin pre-incubation with WSSV particles and inhibited horizontal transmission of WSSV to a certain extent. Considering that the antiviral activity of esculin was stable in the aquacultural water for 2days, we evaluated the dosing pattern of continuous medication changes. Obviously, the survival rate of WSSV-infected shrimps was 0% at 108h when no esculin exchange was made, while at 120h the survival rate was over 40% at continuous medicine changes. In addition, esculin significantly increased the expression of antimicrobial peptides and thus improved the ability of shrimp to resist WSSV. Overall, our findings suggest that esculin has the potential to be developed into an anti-WSSV medicine.

Edoxaban dosing patterns in real life practice – Results from the DRESDEN NOAC REGISTRY

Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism treatment or stroke prevention in atrial fibrillation. Effectiveness and safety of edoxaban depends on adequate dosing, for which renal function, body weight and drug-drug interactions are important. Edoxaban dosing pattern data outside of clinical trials are scarce. Using data from the prospective DRESDEN NOAC REGISTRY we analysed dosing of 1635 edoxaban patients.Between January 2016 and May 2021, 1652 edoxaban treated patients were enrolled and 1635 patients included in the dosing analysis. At baseline, 1257 patients (76.9%) received edoxaban 60 mg daily, 378 patients (23.1%) 30 mg daily. Patients receiving edoxaban 60 mg were more often male, younger and less often had concomitant diseases such as cancer, renal impairment or organ transplantation. Edoxaban dosing was according to label in 1432 (87.6%) and not according to label in 203 patients (6.5% non-recommended 60 mg and 5.9% non-recommended 30 mg). Renal impairment was the dominating reason for dose adjustment, followed by body weight ≤60 kg. Edoxaban dosing was more often adequate in patients younger than 75 years and in male patients compared to older or female patients.Taken together, edoxaban dosing was adequate in up to 90% of patients, with renal impairment being the most important factor for dose reduction. Use of strong P-gp inhibitors was a rare finding and dose reduction was appropriately performed in the majority of these patients. Inadequate dosing seems more frequent in female or older patients and in transplant recipients, indicating areas for further research.

Effect of Pulsed Direct Current on Iontophoretic Delivery of Pramipexole across Human Epidermal Membrane In Vitro.

Pulsed direct current (PDC) iontophoresis, by allowing skin depolarization, was suggested to provide more efficient ion transport, but the extent of its enhancement effect was unclear. PDC could also offer electric-customized drug delivery. This study examined the effect of PDC iontophoresis on transdermal delivery of pramipexole dihydrochloride (PXCl). Iontophoretic delivery of PXCl across human epidermal membrane from pH7.0 solution was conducted in vitro using continuous direct current (DC) and 6- and 12-cycle PDC iontophoresis (0.5mA/cm2 and total applied duration of 6h). Different parameters of PDC iontophoresis were studied, including current density (0.1, 0.2 and 0.5mA/cm2) and on-off current dosing pattern (1h/3h, 0.5h/3.5h, and 0.2h/3.8h). Both 6- and 12-cycle PDC iontophoresis protocols provided modulation of the permeation profile but delivered smaller amounts of PXCl (396 and 400 μg/cm2, respectively) as compared with continuous DC iontophoresis (482 μg/cm2)at 24 h after 0.5 mA/cm2and 180 mA/cm2× min current dose application. Increasing applied current density from 0.1 to 0.5mA/cm2 increased the PDC iontophoretic flux of PXCl linearly from 5.3 to 14.6 μg/cm2·h (R2= 0.887). Varying the current level and duration butat the same applied current dose (36mA/cm2 × min), the total amount of PXCl delivered by PDC iontophoresis at 24 hwas independent of the on-off dosing pattern studied (114-128μg/cm2). The results indicate that PDC iontophoresis can benefit transdermal delivery of PXCl in terms of controlling its permeation but does not enhance iontophoretic transport compared to continuous DC iontophoresis under the conditions studied.

Daratumumab Dose Analysis Among Patients with Multiple Myeloma in a US Community Oncology Setting: A Retrospective Observational Study in Integra Connect Network

BACKGROUND Since the FDA's initial indication for the use of daratumumab in relapsed/refractory multiple myeloma (RRMM) in November 2015, usage has been expanded by subsequent approvals in newly diagnosed, transplant-ineligible MM patients, and more recently in newly diagnosed transplant-eligible patients. Real World Data (RWD) has been published demonstrating daratumumab's efficacy in RRMM settings[1]and its utility of split dosing for the initial dose[2]. However, no study has been published to examine the real-world dosing patterns of daratumumab compared to the FDA standard dosing schedule. While there are minimal variations in the approved dosing schedule of daratumumab, generally accepted dosing is weekly in week 1 through week 8, q 2 Wks in week 9 through week 24, and q 4 Wks after week 24, all at the standard 16 mg/kg dosage[3]. In its approved dosing schedule, adjustments are made in the frequency of administration, but not in the standard weight-based dosing. METHODS Utilizing the Integra Connect database which contains 17 community oncology network accounts and over 1,900 providers in US, we collected all MM patients treated with daratumumab between January 1, 2016 and March 31, 2020. We then excluded any patient whose first line of therapy (LOT) was ambiguous, in order to correctly identify the daratumumab-containing LOTs. We also excluded LOT 1 daratumumab transplant induction due to the wide variation in daratumumab dosing schedules in clinical trials in the transplant eligible patient[4]. LOTs were determined based on International Myeloma Working Group guidelines[5]. Data were collected on the date of each individual daratumumab administration, counting initial split dose, if utilized, as 1 dose. The duration of daratumumab and number of doses administered were calculated and corrected for any time on treatment breaks. The study was conducted per individual patient by LOT cohorts, and for the entire cohort of patients. We utilized the standard dose schedule for daratumumab noted above to establish the expected doses of daratumumab and calculated the compliance dose ratio (ratio of actual doses to expected doses per time on therapy) to evaluate how closely real-world treatment adhered to the standard dosing schedule. RESULTS 1037 MM patients were included with at least 6 doses of daratumumab administration and without stem cell transplant or uncertain LOT. Across all LOTs, the mean duration of daratumumab treatment was 5.6 months with a median duration of 9.8 months. After week twenty-four, 671 (65%) patients remained on daratumumab-containing regimens, with 330 patients continuing q 1 Wk or q 2 Wks dosing, whereas the standard would employ a switch to q 4 Wks dosing (Figure 1). Overall compliance dose ratio was consistently above 100%, implying a significant proportion of patients were receiving more frequent dosing than expected under the standard dosing schedule (Figure 2). We carefully evaluated patients in various LOTs and combination therapies. Drug combination was not found to exert a significant impact on the daratumumab dosing pattern. Compliance dose ratio of daratumumab is slightly higher in RRMM compared to the dose ratio in LOT 1 newly diagnosed MM, but even LOT 1 has a ratio greater than 1 (Figure 3). It should be noted that this increased compliance dose ratio is present in all LOT cohorts despite 25% of patients being started on doses less frequent than weekly (Figure 1). CONCLUSIONS In real-world community oncology practices, daratumumab is utilized in a more frequent dosing schedule than the FDA approved standard dosing. With standard dosing there are 23 daratumumab doses in the first 52 weeks. The compliance dose ratio found in our RWD implies 27.3 doses in the first year for the entire cohort and 26.9 and 28.3 doses in LOTs 2 and 3 respectively. Thus, significantly increased drug and administrative costs are incurred over those anticipated in respect to daratumumab dosing utilization. This study is limited to the EMR and administrative claims data of those individuals who are being treated in a community oncology setting. Residual confounding and bias may exist due to entry error and unobserved patient characteristics.

Treatment Patterns and Characteristics of Individuals Initiating High-Dose Insulin for Type 2 Diabetes Mellitus.

Few studies have examined patient characteristics and treatment patterns of high-dose insulin therapy (> 200 units/day) among patients with type 2 diabetes mellitus (T2DM). To understand patient characteristics, dosing, adherence, and persistence related to high-dose insulin therapy. This was a retrospective observational study that used administrative claims from a large national health plan. Patients were identified who had been diagnosed with T2DM and who were aged 18-89 years, enrolled in a commercial or Medicare Advantage Prescription Drug plan, newly initiated on a total daily dose (TDD) > 200 units of insulin between January 2011 and August 2015. Patients were required to be enrolled 6 months before and 12 months after the index date. Patients were categorized to Regimen-100 if treated with U-100 insulin only or Regimen-500 if treated with U-500R with or without U-100. Baseline demographic and clinical characteristics were evaluated. An adjustment factor for the days supply was calculated as the ratio of median time between insulin claims, and median pharmacy reported days supply for each insulin prescription. Adjusted days supply, quantity, and concentration were used to calculate TDD for each quarter after the index date. Adherence was measured as the proportion of days covered (PDC) for each regimen. Persistence was measured in 2 ways: the percentage of patients remaining on index medications in each quarter and the proportion of patients who maintained TDD > 200 units during all 4 quarters of the 12-month post-index period. We identified 2,339 patients newly titrated up to TDD > 200 units on either Regimen-100 (2,062, 88.2%) or Regimen-500 (277, 11.8%). Patients on Regimen-500 were slightly younger with higher prevalence of comorbidities. The mean TDD (SD) for Regimen-100 decreased from 228.6 (36.0) units during the first quarter to 194.2 (181.4) units during the last quarter. The mean TDD (SD) for Regimen-500 increased from 294.2 (102.2) units in the first quarter to 304.8 (281.6) units in last quarter. The average adherence to the high-dose insulin regimen was 68.2% (30.7; median 72.6%) for the Regimen-100 cohort and 75.5% (27.0; median 85.2%) for the Regimen-500 cohort. In the Regimen-100 and Regimen-500 cohorts, 45.3% and 55.2% had a PDC ≥ 80%, respectively. Only 23.0% and 51.6% of patients maintained TDD > 200 units for the Regimen-100 and Regimen-500 cohorts, respectively, throughout the 4 quarters after the index date. We observed that many patients did not maintain high-dose insulin use over time, especially those on standard U-100 insulin only. This dosing pattern appears to reflect the differences in patient characteristics, insulin needs, and adherence/persistence behavior between those on Regimen-100 and those on Regimen-500. This study was supported by funding from Eli Lilly and Company to Humana as a collaborative research project involving employees of both companies. Chen, Brown, Fan, Taylor, and He are employees of Eli Lilly and Company. Nair and Meah are employees of Humana, which received funding to complete this research. Siadaty was an employee of Humana at the time of this study.

Bioequivalence studies for pharmaceutical products

This review is the summary of Bioequivalence, Bioavailability and its related parameters. Brief description of Bioavailability and Bioequivalence is explained along with the post approval changes. There is a major role played by Bioavailability and Bioequivalence or the development of a drug for generic products. A bioequivalence study is required for generic products so that the rate and extent of drug can be explained which is clinically trivial. The design and conduct of Bioequivalence studies is explained which includes the selection of subject, number of subjects and dosing pattern. This article reviews the role and studies of Bioavailability and Bioequivalence in pharmaceutics.

Use of oral antidiabetic drugs in Japanese working-age patients with type 2 diabetes mellitus: dosing pattern for metformin initiators

Objective: To determine the pattern of antidiabetic drug use, with a particular focus on the metformin dose, among patients with type 2 diabetes mellitus (T2DM) in a Japanese working population.Methods: We used an administrative claims database linked to yearly health check-up data from large corporations. Data were collected for T2DM patients who began using an antidiabetic drug between 2014 and 2017 (n = 20,401). We evaluated the type of antidiabetic drug used and the characteristics of the patients using each type of drug. Among the metformin users, we assessed the titration in its dose or treatment during the 12 month period after initiation at 3 month intervals.Results: Among 20,401 new antidiabetic users, the most frequently used agents during the study period were dipeptidyl peptidase-4 inhibitors (DPP4is; 47.4%), followed by biguanides (18.5%) and sodium glucose cotransporter-2 inhibitors (SGLT2is; 6.7%). Most patients who initiated with metformin were prescribed 500 mg or less daily (72.9%); only 2.0% were prescribed a daily dose of >1000 mg. Moreover, 27% remained on the same daily dose during the 1 year follow-up, whereas another 29.9% discontinued their antidiabetic treatment altogether.Conclusions: A unique pattern of prescription was observed amongst Japanese patients with T2DM, and DPP4is, rather than metformin, were predominantly used as the first-line treatment. SGLT2is were infrequently prescribed. Metformin was prescribed at a daily dose of ≤500 mg in many patients. Greater efforts are needed to assess the comparative effectiveness of these treatment strategies.

DEVELOPMENT OF RENAL DOSING GUIDELINES FOR NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND ANTIBIOTICS - A PROSPECTIVE STUDY

Objectives: The objectives of this study were to determine the impact of renal dosing guidelines on prescribing pattern for nonsteroidal anti-inflammatory drugs and antibiotic in patients with chronic kidney disease (CKD).Methods: This was a prospective interventional study. The study was divided into two phases, pre-intervention and post-intervention phases. Data regarding the kidney function and the pattern of drug dosing will record in the pre-intervention phase. Pocket guides were prepared for the drug dosing in renal impairment and were distributed to clinicians and the pharmacist as a part of intervention. In the post-intervention phase, the dosing pattern of renal eliminated drugs was observed for any improvement. The patterns of dosing of renal eliminated drugs were compared in both the phases.Results: In pre-interventional phase, a total of 43 cases were reviewed, 20 of them were non-hemodialysis (non-HD) (9 female and 11 male) cases with a mean±standard deviation (SD) age of 56.05+8.22 (56) and 23 were undergoing HD (11 female and 12 male) cases with a mean±SD age of 56.72+6.85 (56). In the post-intervention phase, a total of 41 cases were reviewed, 22 of them were non-HD (12 female and 10 male) cases with a mean±SD age of 55.85+6.87 (57) and 19 were undergoing HD (10 female and 9 male) cases with a mean±SD age of 55.77+8.39 (56.6).Conclusion: Health-care professionals have an important responsibility in monitoring the dose for renal impairment patients. Development of renal dosing guidelines for patients hospitalized with CKD can improve the pattern of prescribing in renal failure population.

Non-Feasibility to Estimate the Need for Reversal of Neuromuscular Relaxation from the Applied Rocuronium Dosing Pattern: A Retrospective Analysis of Anaesthesia Records.

Some anaesthetists are convinced that a long interval since the last relaxant dose may be sufficient to recover from anaesthesia without a pharmacological reversal. We intended to demonstrate that the dosing pattern of rocuronium could not predict the necessity of reversal. In a cohort analysis, we retrospectively analysed 180 anaesthesia records of adult patients who underwent elective surgical interventions in general anaesthesia and tracheal intubation with rocuronium-induced neuromuscular blockade. The extracted records were divided to 3 post hoc groups of 60 each, according to the reversal method employed at the end of anaesthesia: group N with neostigmine, group S with sugammadex and group Z without pharmacological reversal. All cases were terminated after achieving a train of four ratio of 0.9. Dosing patterns of rocuronium were compared by applying a novel pharmacometric calculation method, residual drug activity coefficient (RDAC), which employs both the administered individual drug doses in mg kg-1 and the timing of each drug administration in relation to the time of extubation. The rocuronium dosing pattern was correlated with the employed method of neuromuscular blockade reversal. The dosing for rocuronium in patients without pharmacological reversal was lower than that in both reversal agent groups (n=0.58±0.21, S=0.58±0.17 and Z=0.47±0.17), but there was still a large overlap in the RDAC. The dosage profile of rocuronium alone cannot predict the possibility to refrain from pharmacological reversal.

Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.

To evaluate the current NCI-CTEP recommendation and the clinical use of Calvert Formula-derived carboplatin dosing pattern in the treatment of advanced lung cancer patients and assess carboplatin-related toxicity in relation to the degree of dose fluctuation. This retrospective study involved all histologically confirmed inoperable lung cancer patients receiving palliative-intent carboplatin or carboplatin-combination chemotherapy from 2012 to 2016 at Kingston Health Sciences Centre. The carboplatin dosing pattern and carboplatin-related toxicity were collected and analysed on SPSS IBM for Windows version 24.0 (IBM Corp., Armonk, NY, USA). Results were expressed in percentages and P values. Our findings ( N = 75) suggested that 24% of patients had a high-degree of fluctuation in carboplatin dose (>10% variation from initial dose) if carboplatin dose was readjusted with each new creatinine. In practice, 16% of patients had a fluctuation of greater than 10% in ordered dose in the absence of planned dose reductions. Our study found no significant association between prescribed high-risk dosing fluctuation (>10% increased from initial dose) and carboplatin-related toxicities. In contrast to some prescribing recommendations such as NCI-CTEP, our study suggested that most medical oncologists incorporate new serum creatinine in calculating carboplatin dose for each cycle. Only 9% of patients were treated with a fixed dosing pattern (i.e. no fluctuation). Nonetheless, no significant associations were found between high-risk carboplatin dosing fluctuation and its-related toxicity. Whether such practice was due to the forcing function of the computer order entry system (CPOE), or conscious decisions by medical oncologists was unknown. Further analysis in evaluating physicians' preferences and influencing factors on dosing pattern decision would be recommended.

Effects of apatinib dose interruptions on safety and efficacy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting.

142 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]

Phase I/IIb trial: In-situ vaccine for metastatic colorectal cancer.

TPS871 Background: Except for MSI-H tumors, CRC does not respond to immunotherapy. CRC does respond to the graft vs. tumor (GVT) immune effect that occurs after allogeneic stem cell transplantation. GVT is associated with GVHD toxicity which limits the clinical application. A bioengineered allograft (BAG) has been developed which can elicit host-mediated GVT-like effects without GVHD toxicity, chemotherapy conditioning or a HLA-matched donor. BAG are Th1 memory cells derived from blood of healthy donors with CD3/CD28 microbeads attached. These cells have immunomodulatory properties which enable modulation of Th1/Th2 balance and dysregulation of immunosuppressive circuits. We are evaluating the safety and efficacy of BAG in third-line mCRC. Methods: The study uses a standard 3+3 design followed by an expansion phase with the optimal dosing pattern. The protocol has four components: (A) priming; (B) in-situ vaccination; (C) extravasation and trafficking; and (D) counter immune suppression/avoidance. Priming involves intradermal injections of BAG cells which activates NK cells and develops allo-specific Th1/Tc1 immunity. In-Situ vaccination involves tumor cryoablation to release endogenous HSP which chaperone tumor neoantigens, followed immediately by the intralesional injection of BAG cells as adjuvant. Released HSP are engulfed and processed by immature dendritic cells (DC) attracted to the tissue damage. The inflammatory microenvironment created by the BAG and the subsequent allo-rejection response amplified by the priming induces DC maturation. These DC display processed tumor antigens on upregulated MHCI/II and express co-stimulatory CD80/86 enabling priming of a tumor-specific Th1/Tc1 response. CD40L and interferon-gamma expressed by BAG activates allo-specific and tumor-specific memory cells upon intravenous infusion, permitting trafficking to tumor. The host rejection of BAG releases endogenous danger signals creating a sustained systemic inflammatory cytokine release which serves to counter-regulate immunosuppressive mechanisms. Longitudinal CT scans biopsies, PBMC and serum samples are collected for analysis to verify immune events within each phase of the protocol. Clinical trial information: NCT02380443.

High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation.

BackgroundThe correct valganciclovir dose for cytomegalovirus (CMV) prophylaxis depends on renal function estimated by the Cockcroft–Gault (CG) estimated creatinine clearance (CG-CrCl) formula. Patients with delayed or rapidly changing graft function after transplantation (tx) will need dose adjustments.MethodsWe performed a retrospective investigation of valganciclovir dosing in renal transplant patients receiving CMV prophylaxis between August 2003 and August 2011, and analysed valganciclovir dosing, CG-CrCl, CMV viraemia (CMV-PCR <750 copies/mL), leucopenia (<3500/µL) and neutropenia (<1500/µL) in the first year post-transplant. On Days 30 and 60 post-transplant, dosing pattern in relation to estimated creatinine clearance was analysed regarding CMV viraemia, leucopenia and neutropenia.ResultsSix hundred and thirty-five patients received valganciclovir prophylaxis that lasted 129 ± 68 days with a mean dose of 248 ± 152 mg/day of whom 112/635 (17.7%) developed CMV viraemia, 166/635 (26.1%) leucopenia and 48/635 (7.6%) neutropenia. CMV resistance within 1 year post-transplant was detected in three patients. Only 137/609 (22.6%) patients received the recommended dose, while n = 426 (70.3%) were underdosed and n = 43 (7.1%) were overdosed at Day 30 post-tx. Risk factors for CMV viraemia were donor positive D (+)/receptor negative R (−) status and short prophylaxis duration, but not low valganciclovir dose. Risk factors for developing leucopenia were D+/R− status and low renal function. No significant differences in dosing frequency were observed in patients developing neutropenia or not (P = 0.584).ConclusionMost patients do not receive the recommended valganciclovir dose. Despite obvious underdosing in a large proportion of patients, effective prophylaxis was maintained and it was not associated as a risk factor for CMV viraemia or leucopenia.

Common error pathways seen in the RO-ILS data that demonstrate opportunities for improving treatment safety

PurposeThe Radiation Oncology Incident Learning System (RO-ILS) receives event reports from facilities across the country. This effort extracted common error pathways seen in the data. These pathways, expressed as fault trees, demonstrate the need for, and opportunities for, preventing these errors and/or limiting their propagation to treatment. Methods and materialsAs of the third quarter of 2016, 2344 event reports had been submitted to RO-ILS and reviewed. A total of 396 of the reports judged highest priority were rereviewed and assigned up to 3 keywords to classify events. Based on patterns among the keyword assignments, the data were further aggregated into pathways leading to 3 general error types: “problematic plan approved for treatment,” “wrong shift instructions given to therapists,” and “wrong shift performed at treatment.” Fault trees were created showing how different errors at different stages in the treatment process combine to flow into these general error types. ResultsA total of 173 of the 396 (44%) events were characterized as belonging to 1 of these 3 general error types. Ninety-nine events were defined as “problematic plan approved for treatment,” 40 as “wrong shift instructions given to therapists,” and 34 as “wrong shift performed at treatment.” Seventy-six of these events (44%) resulted in incorrectly delivered treatment. Event discovery was by therapists (n = 76), physicists (n = 45), physicians (n = 23), dosimetrists (n = 15), or not identified (n = 9); 5 events were found as a result of the patient questioning the staff. For the event type “problematic plan approved for treatment,” 64 of the 99 (65%) events were attributable to physician error: incorrect target or dosing pattern prescribed. ConclusionsData extracted from RO-ILS event reports demonstrate common error pathways in radiation oncology that propagate all the way to treatment. Additional study and coordination of efforts is needed to develop and share best practices to address the sources of these errors and curtail their propagation.

Evaluation of Prescription Pattern and Quality of life in Acne in Tertiary Care Hospital in North Indian population

Objective: The aim of this study was to evaluate the prescription pattern and Quality of Life of patients and severity of the disease by using Cardiff Acne Disability Index and Global Acne Grading System score respectively. Methods: A cross-sectional study was conducted in North India with 150 samples of patients included into the study. The prescription pattern comprehends the information about the prescribed drugs and also their dosing pattern for different indications that are currently being used in clinical practice. The prescription pattern varies according to the severity of the disease. Results: The cases in the study diagnosed were mostly of acne vulgaris (96.7%), followed by acne conglobata (1.3%), acne rosaceae (1.3%) and acne fulminans (0.7%). Conclusion: It was noted that oral Isotretinoin was the drug of choice for the treatment of moderate and severe forms and antibiotics included into the therapy were minocycline, clindamycin, azithromycin and erythromycin for mild and severe forms. There was not a strong degree of association between therapy and improvement in Cardiff Acne Disability Index and Global Acne Grading System but by observing overall Cardiff Acne Disability Index improvement it can be estimated that the prescription practice used for therapy enhances Quality of Life of the patient.

Philosophical Issues and Psychological Variables that Influence the Determination of Opioid Effectiveness: A Narrative Review

Background: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked. Objectives: This manuscript provides a selective review and narrative summary of the philosophical issues and psychological factors which can influence opioid effectiveness. Study Design: A selective review and narrative analysis of the literature. Methods: Experimental and clinical-based studies examining the impact of psychological factors on the effectiveness of opioids were extracted from the literature. Studies in which psychological factors were used as an independent variable were given preference. Results: The philosophical issues reviewed include: (a) one’s understanding of the nature of chronic pain, (b) the meaning of the score on the pain numerical rating scale (NRS), and (c) the selection of outcome measures. The psychological factors found to influence the effectiveness of opioids include: (a) role conditioning and learning, especially as they relate to conditioned analgesia, non-associative tolerance, and the nocebo effect, (b) dosing pattern, (c) patient specific factors, e.g., mood, overall psychological and neurocognitive status, (d) social variables, e.g., personal environment and the media, and (e) the dysfunctional endogenous opioid system and its relationship to various psychological disorders. Limitations: This is a selective review of the literature. Some of the hypotheses presented have not been experimentally validated. The review includes animal, human, experimental, and clinical studies. Conclusions: In general, the effectiveness of opioids may be influenced as much by the overall context in which they are used, including the physician-patient relationship as well as their pharmacological properties. Data obtained from short-term and well-controlled trials may not generalize to the clinical setting, which is often more complex and dynamic. Appreciating the impact of psychological factors may assist the clinician in proper patient selection, monitoring, and improved outcomes. Key words: Psychological factors, philosophical issues, chronic pain, opioid therapy, effectiveness, conditioning, placebo, cognitive dysfunction

Stereotactic radiotherapy of the prostate: fractionation and utilization in the United States.

PurposeTo analyze the utilization and fractionation of extreme hypofractionation via stereotactic body radiotherapy (SBRT) in the treatment of prostate cancer.Materials and MethodsData was analyzed on men diagnosed with localized prostate cancer between 2004–2012 and treated with definitive-intent radiation therapy, as captured in the National Cancer Database. This database is a hospital-based registry that collects an estimated 70% of all diagnosed malignancies in the United States.ResultsThere were 299,186 patients identified, of which 4,962 (1.7%) were identified as receiving SBRT as primary treatment. Of those men, 2,082 had low risk disease (42.0%), 2,201 had intermediate risk disease (44.4%), and 679 had high risk disease (13.7%). The relative utilization of SBRT increased from 0.1% in 2004 to 4.0% in 2012. Initially SBRT was more commonly used in academic programs, though as time progressed there was a shift to favor an increased absolute number of men treated in the community setting. Delivery of five separate treatments was the most commonly utilized fractionation pattern, with 4,635 patients (91.3%) receiving this number of treatments. The most common dosing pattern was 725 cGy × 5 fractions (49.6%) followed by 700 cGy × 5 fractions (21.3%).conclusionsExtreme hypofractionation via SBRT is slowly increasing acceptance. Currently 700-725 cGy × 5 fractions appears to be the most commonly employed scheme. As further long-term data regarding the safety and efficacy emerges, the relative utilization of this modality is expected to continue to increase.

Advance of DNA and CCPs-based nanocarriers in drug delivery systems.

Development of smart and functional polymeric carriers, which enable controlled or timed release of a bioactive material, thereby providing a better dosing pattern and minimizing side effects, becomes a new requirement in the field of drug delivery. In the recent few decades, a great many advancements of polymer synthetic methods have led to a new generation of bioactive polymers' applications as drug controlled release carriers. In this review, we focus on the use of bioactive polymers for drug delivery system, with a particular in the utility of DNA-based nanocarriers and cell-penetrating peptides (CCPs)-based nanocarriers to provide precision control for drug targeting or stimuli responsive systems.

Long-Term Dosing of Intrathecal Baclofen in the Treatment of Spasticity After Acquired Brain Injury

BackgroundIntrathecal baclofen (ITB) often is used to treat severe spasticity of cerebral origin. Although literature exists regarding the efficacy of ITB, there has been minimal investigation related to dosing in the adult-acquired brain injury population, particularly at long-term duration. ObjectiveTo investigate long-term dosing of ITB in adult patients with spasticity of cerebral origin due traumatic brain injury (TBI), stroke, and hypoxic-ischemic encephalopathy (HIE). DesignRetrospective cohort study. SettingAn academic outpatient rehabilitation clinic. PatientsForty-two adult patients with spasticity secondary to TBI, stroke, or HIE treated with ITB for greater than 3 years. MethodsMedical records and device manufacturer records of included patients were reviewed to obtain demographic data, dosing information, dates of pump and catheter placements, and revisions. Main Outcome MeasureAverage daily ITB doses and mean change in ITB dose over 1, 2, and 3 years. Goal of ITB treatment (active function versus comfort/care/positioning) also was compared. ResultsOf 42 total patients, spasticity was attributed to either TBI (n = 19), stroke (n = 11), or HIE (n = 12). The mean (standard deviation) age was 35.21 (10.17), 56.7 (13.1), and 35.1 (12.4) years for the TBI, stroke, and HIE groups, respectively (P < .001). There was a significant difference in the goal of therapy with “improving functional independence,” accounting for 27.8%, 72.8%, and 0% in the TBI, stroke, and HIE groups, respectively (P = .002). The mean duration of ITB therapy was 8.5 (5.0), 7.8 (3.4), and 9.1 (4.6) years in the TBI, stroke, and HIE groups, respectively (P = .79). The mean daily ITB dose was 596.9 (322.8) μg/d, 513.2 (405.7) μg/d, and 705.2 (271.7) μg/d for the TBI, stroke, and HIE groups, respectively (P = .39). In the subset of the cohort with ITB therapy for more than 5 years, the mean percent change in daily ITB dose between time of chart review and 1, 2, and 3 years previously was 7.3% (13.6), 12.7% (16), and 24.7% (50.3), respectively. A complex dosing pattern was used more frequently in those with stroke (36.4%) compared with the TBI and HIE (9.7%) groups (P = .04). ConclusionDespite the long-term use of ITB therapy in this cohort, the mean daily dose of ITB continued to require adjustments. There was no significant difference in the mean daily dose between patients with a diagnosis of TBI, stroke, or HIE. A complex dosing pattern was used more frequently in patients with stroke. Level of EvidenceIII

Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.

Context:Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect.Aim:This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients.Design:Retrospective cohort study.Materials and Methods:Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria.Statistical Analysis:P < 0.05 was considered as statistically significant.Results:Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058).Conclusion:Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity.