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World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) d...

Background There is a growing number of pediatric procedures requiring sedation outside the operating room. Among these are auditory brainstem response (ABR) tests, the gold standard for objective hearing evaluation in infants and toddlers. Recently, a nurse-led pediatric sedation service based on a structured protocol has been developed for ABR testing. Objectives To retrospectively analyze the safety and efficacy of the pediatric nurse-led sedation protocol (PNLSP) in a tertiary medical center using Chloral Hydrate (CH) in children undergoing ABR testing. Methods Data from medical charts of children who underwent sedation for ABR testing between January 2014 and December 2017, were retrieved. Analysis of sedation success/failure rates, sleep induction time (SIT), sleep duration time (SDT), and adverse events (AE), was performed. Findings 1348 children with a mean age of 13.4 months (range 3–42 months), classified by the American Society of Anesthesiologists Physical Status Classification System (ASA score) 1–3, were included in the analysis. All children received a fixed dose of 75 mg / kg CH orally or rectally. Sedation success rate was 98.7% and enabled completion of ABR testing. Failure to sedate was evident in 17 children (1.3%), all classified as ASA score 1–2. Median SIT and SDT were 25 and 100 min, respectively. Mild AE occurred in 9 children (0.67%), none of which required further intervention. Conclusions Findings support the use of a structured PNLSP using CH as safe and efficient. The suggested protocol is an effective alternative for general anesthesia (GA) for ABR testing in healthy young children.

The review deals with a new form of oral antidiabetic drugs with a fixed dose — the combination of sustained-release metformin and glimepiride. Amaryl®M SR (2/500 mg) — a new dosage form, which provides a rapid release of glimepiride, and then the slow release of metformin from multipolymer hydrophilic matrix independently of pH. Based on the research of therapeutic efficacy and bioavailability, it is shown that this form is characterized by an optimal pharmacokinetics of metformin and glimepiride, does not increase the incidence of hypoglycemia, may be administered once a day, and is associated with less severe gastrointestinal side effects, as well as has more pronounced compliance. Application of Amaryl®M SR creates new possibilities for patients with type 2 diabetes mellitus in terms of optimizing glycemic control and quality of life., Обзор посвящен новой форме пероральных антидиабетических препаратов с фиксированной дозой — комбинации метформина замедленного высвобождения и глимепирида. Амарил®М СР (2/500 мг) — новая лекарственная форма, обеспечивающая быстрое высвобождение глимепирида, а затем медленное высвобождение метформина из мультиполимерного гидрофильного матрикса независимо от рН. На основании исследования терапевтической эффективности и биодоступности показано, что данная форма характеризуется оптимальной фармакокинетикой метформина и глимепирида, не приводит к увеличению частоты гипогликемий, может назначаться однократно в сутки и ассоциирована с меньшей выраженностью желудочно-кишечных побочных эффектов, а также с большей приверженностью к лечению. Применение Амарила®М СР создает новые возможности для больных сахарным диабетом 2-го типа относительно оптимизации гликемического контроля и качества жизни., Огляд присвячений новій формі пероральних антидіабетичних препаратів із фіксованою дозою — комбінації метформіну сповільненого вивільнення та глімепіриду. Амарил®М СР (2/500 мг) — нова лікарська форма, що забезпечує швидке вивільнення глімепіриду, а потім повільне вивільнення метформіну з мультиполімерного гідрофільного матриксу незалежно від рН. На підставі дослідження терапевтичної ефективності та біодоступності показано, що ця форма характеризується оптимальною фармакокінетикою метформіну та глімепіриду, не призводить до збільшення частоти гіпоглікемій, може призначатися одноразово на добу й асоційована з меншою вираженістю шлунково-кишкових побічних ефектів, а також із більшою прихильністю до лікування. Застосування Амарилу®М СР створює нові можливості для хворих на цукровий діабет 2-го типу щодо оптимізації глікемічного контролю та якості життя.

Purpose Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy. Methods We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO2/FiO2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h. Results A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318–528] compared to both the TOF: 665 [IQR 472–927] and the FD arms: 1730 [IQR 1695–1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points. Conclusion Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen.

Objectives: We analyzed patient-reported sleep parameters for an extended-release methylphenidate formulation (PRC-063) in adolescents with attention-deficit/hyperactivity disorder. Methods: Clinic...

Objective Gynaecological cancer surgery is associated with high rates of venous thromboembolism (VTE) despite recommended prophylaxis. We sought to investigate the impact of extended prophylaxis with fixed dose and weight based LMWH in patients undergoing gynaecological cancer surgery. Methods VTE rates were recorded in patients who received LMWH prophylaxis (4500 IU Tinzaparin once daily) for the duration of hospital stay (2006–2012) (n = 610) and were compared with VTE rates in patients who underwent surgery after the introduction of extended prophylaxis (3500/4500 IU Tinzaparin for patients with BMI 40 kg/m2) (2012–2017) (n = 651). Peak (4 h) anti-Xa levels in a subset of patients were also evaluated. Results 73 (5.7%) cases of VTE were recorded during 1 year of follow-up. 20 cases occurred during hospital stay. There was no significant difference in the rate of VTE between the extended prophylaxis cohort and the standard prophylaxis cohort. 23/24 patients who developed VTE in the extended prophylaxis cohort received a fixed (4500 units) dose of Tinzaparin. 63% of patients who received a fixed LMWH dose had peak anti-Xa levels below the target range (0.2–0.4 IU/ml). Peak anti-Xa was lower in patients who subsequently developed VTE compared with those who received either fixed dose (P = 0.041) and weight adjusted Tinzaparin (P = 0.0006). Conclusions Extended prophylaxis with Tinzaparin does not significantly reduce VTE rates in gynaecological cancer patients post surgery. Peak anti-Xa levels may be suboptimal in many patients receiving a fixed LMWH dose. Further studies are required to determine whether weight adjusted doses of Tinzaparin may provide more effective prophylaxis following gynaecological cancer surgery.

Background: Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson’s disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.

To compare the ventilatory and clinical outcomes associated with a fixed-dose cisatracurium infusion versus a titrated infusion strategy in patients with Acute Respiratory Distress Syndrome (ARDS).Single-center, retrospective, cohort study in a medical ICU of a tertiary care academic medical center. Adult patients ≥18 years old with a continuous infusion of cisatracurium for ≥12 h for treatment of ARDS were included. The primary outcome was the PaO2 /FiO2 ratio assessed at 24 and 48 h following cisatracurium initiation. Secondary outcomes included amount of average dose of drug administered, 28-day ventilator-free days, LOS, and hospital mortality.167 patients were included; median baseline PaO2/FiO2 was 97 (76-146), median SOFA score of 9 (7-11), and ICU mortality was 71/167 (43%). In a mixed-effects model, fixed dose and titrated cisatracurium associated with similar changes in PaO2/FiO2 assessed at 24 and 48 h (p = 0.316). Fixed-dose was associated with a3-fold increase in drug exposure (average dose 6.4 (5.4-8.0) vs. 2.0 (1.5-2.8) mcg/kg/min; p0.001, respectively). No differences were observed in secondary clinical endpoints.Fixed-dose cisatracurium was associated with similar ventilatory and clinical outcomes compared to titrated strategy, yet it was associated with a 3-fold increase in dose administered.

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.

Fixed-dose prothrombin complex concentrates (PCCs) for the reversal of vitamin K antagonists may decrease the incidence of thromboembolic events, treatment costs, and treatment delays. However, the ideal fixed dose is unknown, with some studies showing inadequate reversal with suboptimal dosing or in patients with a higher international normalized ratio (INR) or weight. This indicates a need for a modified fixed-dose strategy that considers weight and INR. This study was a retrospective chart review comparing efficacy and safety outcomes of the standard variable-dose protocol versus a fixed-dose protocol. The primary outcome was the proportion of patients who achieved INR reversal. Of the total of 113 patients reviewed, INR reversal to

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase

The aim of the current study work was to formulate and assess a fixed dose mixture tablet of instant release oral solid dosage form comprising two anti-diabetic drugs (linagliptin and metformin hydrochloride) for managing of diabetes mellitus type 2.The innovator drug product (Jentadueto Tablet) was evaluated for the various evaluation parameters, which have been taken into consideration during the drug product development. Pre-formulation evaluation was accomplished to safeguard better parameters of formulated drug product. On the result of pre-formulation evaluation and innovator drug product characterization, the model drug product was recognized in various steps. The established formulation was augmented for different excipients. The instant release film covered tablet of linagliptin and metformin HCl was expressed and augmented at laboratory scale. The individual steps (procedures) were improved for the same and the scale-up contemplation have been engaged into account certify the product performance at pilot plant-up to commercial scale-up. Keywords: anti-diabetic, linagliptin, metformin

RATIONALE: Reducing nicotine content in cigarettes to ≤ 2.4 mg per g of tobacco [mg/g] reduces smoking behavior and toxicant exposure among adult daily smokers. However, cigarettes with similar nicotine content could support continued experimentation and smoking progression among young adults who smoke infrequently. OBJECTIVES: This study evaluated the threshold for nicotine in cigarettes that produces reactions associated with smoking progression in a sample of young adults who smoke infrequently. METHODS: Young adults (n=87, 18-25 years, 49% female) using tobacco products ≤15 days per month completed three counterbalanced, double-blinded sessions, each measuring Positive and Negative subjective reactions to fixed doses of smoke from investigational cigarettes containing one of three different nicotine contents: normal (NNC; 15.8 mg/g); very low (VLNC; 0.4 mg/g); and intermediate (INC; 2.4 mg/g). In a final session, participants chose one of the cigarettes to self-administer. RESULTS: Post-cigarette breath carbon monoxide was greater for VLNC than for NNC (p

Objective. The aim of this study was to understand whether enhanced CT can provide more information than unenhanced CT on diagnosis of sarcopenia. Materials and Methods. We reviewed the enhanced CT data of 45 patients of pancreatic cancer. Manual tracing of the psoas muscles was used for measuring the cross-sectional muscle areas and attenuation at umbilicus level; afterwards, PMI, PMD, and Δ PMD were calculated. Results. In the unenhanced scanning, arterial, venous, and parenchymal phases of enhanced CT, PMI values were 6.905 ± 2.170, 6.886 ± 2.195, 6.923 ± 2.239, and 6.866 ± 2.218, respectively, and the difference was not statistically significant. The PMD values at different phases were 34.311 ± 7.535, 37.487 ± 7.118, 40.689 ± 7.116, and 42.989 ± 7.745, respectively, which were gradually increased, and the difference was statistically significant. Meanwhile, the PMD of arterial phase, venous phase, and parenchyma phase showed a linear correlation with PMD of unenhanced scanning phase. 31 patients had low PMD and 14 had normal PMD during the unenhanced scanning phase. With the addition of contrast agent, ΔPMD values increased faster in the low PMD group than in the normal PMD group during the venous and parenchymal phases (7.048 ± 3.067 vs 4.893 ± 2.558; 9.581 ± 3.033 vs 6.679 ± 2.621; p < 0.05 ), which made the gap between PMD after contrast-enhancement vs. unenhanced scanning smaller. Conclusion. The use of contrast agent has no effect on the manually measured PMI values but can change the results of PMD. This change makes the difference of PMD in different enhancement phases smaller than that in plain scan phase and furthermore increases the examination cost; therefore, it is not recommended to use enhanced CT routinely with fixed dose administration of contrast agent for patients’ assessment of PMI and PMD.

The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown. We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model. Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose. The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.

In this study, acute toxicity of kenikir leaf (Cosmos caudatus HBK) ethanolic extract was conducted on Wistar white male rats with fixed dose procedure. The extraction method used was maceration using 70% ethanol. A dose of 2000 mg/kgBW was determined as the starting dose based on the preliminary test result. The rats used in the main test were divided into the normal group and the 2000 mg/kgBW dose group, each used five animals in each group. The results of the test showed that there were no deaths or toxic symptoms both of the normal group and the 2000 mg/kgBW dose group. The conducted preliminary test results a dose of 2000 mg/kgBW as the starting dose. Next, main test is done toward two groups of rats: Normal group and 2000 mg/kgBW dose group each consist of five animals. The main test results in neither deaths nor toxic symptoms from those groups. The range of toxic doses of kenikir leaf ethanolic extract that can cause acute toxicity is >2000 mg/kgBW, and hence, this experiment classified in the practically nontoxic category. Statistical analysis on effect to macroscopic organs of the liver, heart, and kidney showed no significance (P > 0.05) from kenikir leaf ethanolic extract. Average levels of biochemical parameters from the 2000 mg/kgBW group and the normal group were in the normal range. Ethanolic extract at a dose of 333 mg/kg BW does not cause severe pancreatic damage, and hence, it is considered safe for use as an antidiabetic.

Cemiplimab, a human monoclonal antibody targeting programmed cell death-1 (PD-1) receptor, demonstrated antitumor activity in patients with advanced malignancies and a safety profile comparable to other anti–PD-1 therapies. This population pharmacokinetics (PopPK) analysis of cemiplimab included 11,178 pharmacokinetics (PK) observations from 548 patients pooled from a first-in-human study (Study 1423; NCT02383212) in advanced malignancies and a Phase 2 study (Study 1540; NCT02760498) in advanced cutaneous squamous cell carcinoma (CSCC). Most patients (80.3%) received cemiplimab 3 mg/kg every 2 weeks (Q2W) intravenously (IV). A PopPK model was developed by evaluating two-compartment linear models with an empirical non-linear function describing time-varying change in cemiplimab clearance and covariates that improved goodness-of-fit. PopPK simulations were used to describe cemiplimab exposure generated by a fixed 350 mg every 3 weeks (Q3W) IV dose regimen. PopPK modeling showed that a two-compartment model with zero-order IV infusion rate and first-order elimination rate well described individual concentrations of cemiplimab. Although several covariates, including baseline body weight and albumin concentrations, had a modest impact on cemiplimab exposure, the magnitude of influence was within the typical observed PK variability of approximately 30%. Based on PopPK simulation results, the 350 mg Q3W dose regimen was selected for further studies in advanced malignancies, including advanced CSCC. Similarity in observed cemiplimab exposure at the fixed 350 mg Q3W and the weight-based 3 mg/kg Q2W dose regimens confirmed this fixed dose selection. A robust PopPK model was developed to describe cemiplimab concentrations and supported use of the fixed 350 mg Q3W IV dose regimen. Supplementary Information The online version of this article (10.1007/s10928-021-09739-y) contains supplementary material, which is available to authorized users.

In a previous study, dasotraline demonstrated efficacy at a dose of 8 mg/day in adults with attention deficit hyperactivity disorder (ADHD). The aim of the current study was to evaluate the efficacy and safety of dasotraline in doses of 4 and 6 mg/day. Adults meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for ADHD were randomized to 8 weeks of double-blind, once-daily, fixed-dose treatment with dasotraline 4 mg/day, 6 mg/day, or placebo. The primary efficacy endpoint was changed in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy endpoints included the Clinical Global Impression, Severity (CGI-S) Scale. Least squares mean reduction at week 8 in the ADHD RS-IV HV total score was not significantly greater (vs. placebo) in the dasotraline 4 mg/day group (-15.0 vs. -13.9; n.s.; or in the dasotraline 6 mg/day group (-16.5 vs. -13.9; P = 0.074; Hochberg correction). Treatment with dasotraline 6 mg/day was significant at week 8 (uncorrected) on the ADHD RS-IV total score (P = 0.037) and the CGI-S score (P = 0.011). Treatment with the 4 mg/day dose of dasotraline was NS. Treatment with dasotraline was generally well tolerated. The results provide additional evidence that supports the potential efficacy of dasotraline, in doses of 6 mg/day, in adults with ADHD.

In order to improve the effectiveness of antihypertensive treatment, doctors more often prescribe fixed dose combinations of two or three antihypertensive products. In this case, the concomitant effects of these products contribute to better control of blood pressure, improve patient’s adherence to treatment and reduce the risk of side effects. The fixed dose combination of lercanidipine and enalapril is quite new for Ukrainian physicians; however, there is already a sufficient evidence base for the efficacy and safety of such combination therapy. Lecranidipine – enalapril combination reduce systolic and diastolic blood pressure in patients with moderate hypertension without severe side effects. In addition, this combination is effective and safe in patients with comorbidities.

Suicidal patients often present to the emergency department, where specific anti-suicidal treatment is lacking. Ketamine, a Glutamate modulator and a rapidly acting antidepressant with anti-suicidal properties, might offer relief.Evaluation of single, fixed-dosed intranasal ketamine for acute suicidal ideation in the emergency department.Between August 2016 and April 2018, 30 eligible suicidal subjects, scheduled for psychiatric hospitalization, independently of their psychiatric diagnosis, were randomized to intranasal ketamine 40 mg or saline placebo. Safety and efficacy evaluations were scheduled for 30, 60, 120 and 240 min post administration and on days 1, 2, 3, 4, 5, 7, 21 and 28. Primary outcome was suicidal ideation.Fifteen subjects were randomized for each study group. All were analyzed for primary and secondary outcomes. Four hours post administration, the mean difference in suicidal symptoms between the groups, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) item of suicidal thoughts (MADRS-SI), was 1.267 (95% confident interval 0.1-2.43,Single, fixed-dose, intranasal ketamine alleviated suicidal ideation and improved depressive symptoms four hours post administration. We present here an innovative paradigm for emergency department management of suicidal individuals. Future larger-scale studies are warranted.

Objective: To explore the prokinetic effect of Ranitidine, to compare it with the prokinetic effect of Neostigmineand to observe the potentiating prokinetic effect of Ranitidine and Neostigmine in combination. Study Design: Randomised controlled trial (experimental study). Place and Duration of Study: Multi disciplinary centre, Army Medical College, Rawalpindi, from Jan to Dec 2015. Methodology: Experiments were performed on three groups of rabbits (n=6) and Cumulative dose responsecurves were plotted using isolated duodenal tissue on power lab (USA). In the first two groups of experiments,cumulative concentrations of Neostigmine and Ranitidine were studied separately with neostigmine acting as acontrol and in the third group the potentiating effect of a fixed dose of ranitidine on neostigmine was evaluated. Results: Neostigmine’s response was taken as 100 percent and Ranitidine’s response when compared to it came out to be 197 percent. The dose response curve of Neostigmine was shifted to the left and upwards in the presence of Ranitidine. The percent response with Neostigmine alone was taken as 100 percent and increased to 212 percent when the tissue was pre-treated with Ranitidine. Conclusion: Our study has indicated that Ranitidine has marked prokinetic effect which is found to be greaterthan Neostigmine. It is also inferred that Ranitidine can potentiate the prokinetic effect of Neostigmine.

WHAT IS KNOWN AND OBJECTIVE Therapeutic alternatives to simplify antiretroviral therapy (ART) in HIV-infected children are needed. We report our experience with abacavir(ABC)/lamivudine(3TC) individualized dose compounded capsules (IDCC). COMMENT We present a prospective case series of HIV-infected children who did not weigh enough to receive the adult fixed-dose combination including ABC/3TC 600mg/300mg, and were treated with weight-adapted ABC/3TC IDCC in Barcelona, Spain. Thirteen patients (12 girls) received ABC/3TC IDCC for a median(IQR) time of 30(17-54) months. No significant changes were observed in CD4 cell counts, weight or height z-scores over time. Suppression of viral replication was maintained in 7 patients with undetectable viremia at baseline. Another 5 patients achieved viral suppression with ABC/3TC IDCC-based ART, while one non-adherent girl did not. No adverse events related to ABC/3TC IDCC were observed. WHAT IS NEW AND CONCLUSION Despite small numbers, the long-term use of ABC/3TC IDCC was feasible, safe, and effective in the treatment of HIV-infected children.

Introduction The phase 2 POPLAR and phase 3 OAK studies of the anti–programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials. Methods POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m2) every 3 weeks. Efficacy and safety outcomes were evaluated. Results A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58–1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68–0.89). The 4-year OS rates in POPLAR were 14.8% (8.7–20.8) and 8.1% (3.2–13.0) and those in OAK were 15.5% (12.4–18.7) and 8.7% (6.2–11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively. Conclusions Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies.

Objective: Migraine headaches are one of the most common and debilitating diseases. Chronic migraine (CM) is a type of migraine that reduces quality of life and causes disability. Botulinum toxin A (BT-A) was approved in 2010 by the Food and Drug Administration for CM as one of the treatment options. In BT-A treatment, follow the pain (FTP), fixed-site fixed-dose (FSFD) methods, and combined injections are prevalent. This clinical trial aimed to compare the effects of two methods of BT-A injections in patients with CM to determine the method with the fewest complications, the strongest therapeutic effects, and the lowest costs in improving quality of life. Materials and Methods: In this preliminary clinical trial, 40 patients with CM were screened, and after examining the inclusion criteria, 18 patients completed the trial. After a baseline examination and experiencing a 28-day baseline period, they were randomly divided into FSFD and FTP groups. In our study, we used the Quality of Life Questionnaire, the Migraine Daily Note, and Headache Impact Test-6. Results: A total of 17 women and 1 man completed the trial. Severity and rate of headaches and quality of life scores had better changes in the following months with similar trends in both groups without a significant difference. Conclusion: The comparison of the scores showed an improvement in most patients, but there was no significant difference between the FSFD and FTP groups. However, the results indicated a greater response to the treatment and a higher rate of drug use in the FSFD group.

Self-medication is widely practiced everywhere in the world. The drug for self medication has proven efficacy and safety for short-term use in minor illnesses but there is the potential for misuse and abuse of them. A cross sectional survey was conducted by visiting 800 houses of Anand district of Gujarat. The details regarding self medication were inquired which include the medical conditions for which they used, availability of Fixed Dose Combinations (FDCs), previously prescribed medicines taken as self medication, sources, reference & reasons for self medication. The Knowledge of the study participants regarding Self medication was inquired by revealing the history of illness in past six months. Ethics Committee approval was taken prior to the study. A total of 501 without prescription medicine formulations were found in 245 (30.63%) houses, more in the urban area (38.25%) than the rural (23%). The common conditions for self medication were body ache, arthritis and fever (36.53%). The commonest source was pharmacy stores whereas family, friends or relatives were commonest sources of information for self medication. The Self decision was taken for 32.93% of medicines. Total 43 medicines prescribed earlier were used as self medication for other family member including 12 preparations for pediatric use. Only 126 participants had 222 illness episodes in past six month. Of them 18 study respondents self medicated. Half of the respondents were having the knowledge regarding medicine. There is a need of emphasizing on proper awareness and education related to self-medication. Keywords: Self-medication, Medicines without prescription, Rural, Urban.

Fasika Berhanu Tola,1 Gizachew Tilahun Anbessa,2 Berhan Begashaw Yikna3 1Curative and Rehabilitative Core Process Section, Dire Dawa City Administrative Health Bureau, Dire Dawa, Ethiopia; 2School of Pharmacy, Faculty of Health Science, Jimma University, Jimma, Ethiopia; 3Department of Pharmacy, College of Health Science, Debre Berhan University, Debre Berhan, EthiopiaCorrespondence: Berhan Begashaw Yikna Tel +251-919-365-179Email berhan.uog1912@gmail.comBackground: Health facilities (HFs) need extensive ranges of anti-tuberculosis (TB) drugs and related TB laboratory commodities (LCs) for diagnosis, prevention, and treatment of TB and multi-drug-resistance (MDR)-TB. This study was aimed to assess anti-TB commodities management performance at public HFs of Dire Dawa city administration, Ethiopia.Methods: A cross-sectional study design in 16 HFs providing TB and MDR-TB related service using quantitative and qualitative method was conducted. Semi-structured questionnaires and observation checklists with logistic indicators assessment tools were used to collect data. We used an in-depth interview and analyzed using a thematic approach. Quantitative data were entered into Epi-Data version 3.1 and transported to SPSS version 20 to analyze the results. Chi-square was used to test the association and a P-value< 0.05 was statistically significant.Results: The majority(13; 81.3%) of HFs used a health commodity management information system. Forty-two (40%) bin cards (BCs) for first line anti-TB drugs were not updated, while 62.5% of BCs were updated for second line drugs. On average, 43% of HFs accurately reported a report and requisition format (RRF) had significant association with the presence of a logistic management information system (LMIS) and standard operating procedure (P=0.019). Of the HFs, 50% had good storage conditions and guidelines (P=0.041). Regimen change (56.3%; P=0.035), receive near expiry (56.3%; P=0.035), and defective practice to first expired-first-out (50%; P=0.007) were reasons for wastages. About 50% and 66.6% of HFs were stocked out for isoniazid 300 mg, rifampicin, isoniazid, pyrazinamide (RHZ fixed dose), and ethambutol 400 mg with a mean stock out duration of 10.8, 18.9, and 70.5 days, respectively. Regimen change (68.8%; P=0.026), low demand (56.3%; P=0.041), and delay to resupply (37.5%; P=0.041) were reasons for stock out of anti-TB commodities.Conclusion: Anti-TB drugs and LCs management performance of the HFs were found to be defective, which was confirmed by unsatisfactory data records, inconstant reports, deprived stock record accuracy, long lead time, high stock out rate, wastages, defective storage conditions, lack of training, and management support. Hence, respective organizations should improve their responsible activities to secure an uninterrupted supply of anti-TB drugs and LCs.Keywords: anti-TB drugs, MDR-TB, laboratory commodities, health facilities, Ethiopia

Objective Radioiodine (131I) is an established modality of definitive treatment of hyperthyroidism. In spite of the vast experience available, there are still several aspects to be clarified, such as whether fixed or calculated doses should be used. The aim of this study was to assess whether efficacy of this treatment could be improved by implementing a simple dosimetric calculation method including ultrasonographic estimation of thyroid volume and a single measurement of 24-h 131I thyroid uptake. Methods A prospective non-inferiority study was designed to compare two procedures to calculate radioiodine activity: the “semi-fixed” dose method (A), and the “calculated” dose method (B). The first consisted of activity escalation (185 MBq steps) based on etiology of hyperthyroidism, 131I uptake, and treatment objective. The second method was based on the “dosimetric compromise” concept, considering 24-h uptake and thyroid volume as the only factors and using a standard half-life of 5.5 days. The target absorbed dose was 150 Gy, but after a preliminary analysis (first 100 cases) it was increased to 200 Gy in diffuse toxic goiters (DTGs). Results A total of 212 patients were included. Method B was at least as effective in terms of final and functional outcome, with a trend to more success and less hypothyroidism. In addition, activities administered were significantly lower. Conclusion In radioiodine therapy of hyperthyroidism, a simple dosimetric method that provided results at least equal to those of a fixed dose-based method, with lower administered activities, could be implemented.

Treatment with 131I is one of the standard treatments for benign thyroid disease. In most cases, the prescribed dose is specific for the same disease. Inspired by external radiotherapy, the emergence of personalized pre-therapeutic dosimetry in nuclear medicine departments makes it possible to adapt to the patient's diseases and physiology; more specific to its kinetics of iodine distribution. By personalizing the prescribed activity, dosimetry makes it possible to comply with the ALARA principle in metabolic radiotherapy while at the same time preserving the therapeutic objective. Post-treatment dosimetry permits to validate the methodology and, by recording the dose actually delivered to the organs surrounding the target volume, to contribute to the understanding of the dose-effect relationship. A re-reading of the MIRD formalism guidelines is important as this document lists the procedure to be followed in thyroid dosimetry. Defining the sensitivity, calculating the S factors, estimating the cumulative activity and residence times and then calculating the dose are the different steps presented. The need to switch from fixed dose prescription to personalized prescription seems to be evident. Several studies in progress as well as the emergence of new software compiling all the information essential for its implementation will permit nuclear medicine departments to involve themselves more easily into the process.

Introduction Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. Methods This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. Results A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. Conclusion A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Kasa (Cough) is one of the most frequent symptoms in pediatric age group for which parents look for medical care. It indicates that even after advancements in current medical science, cough is not being effectively controlled in children. With the above background, the present trial was aimed to study the efficacy of herbal tablet named as Shwasa Kasadi gutika in the management of Kasa. The objectives of the study were to assess the efficacy of trial drug on Kasa and its subjective and objective parameters.The study was a single group, single centre, fixed dose, interventional study. The subjective parameters were as per the clinical features of Kasa. Their grading was done as per their intensity. School going age group was more likely to suffer from the cough and male children were more in the study. There was significant improvement in all subjective criteria where as significant changes were noted in adventitious sounds and total leukocyte count. However, as it was conducted in limited samples, further large sample multi-centre studies would be preferable. Developing pharmaceutical standards of the tablet would also be a newer area of research.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all‐cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP 60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed‐dose combinations (FDCs) of BP‐lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP‐lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP‐lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies.

To assess the cost-effectiveness of single pill fixed dose triple combination therapy vs. free triple combination therapy for the prevention of cardiovascular events among patients with hypertension.A Markov model with a five year cycle was constructed. Two decision models incorporating strict and more relaxed adherence definitions estimated quality adjusted life years (QALYs) and health-care costs for single pill fixed triple combination therapy vs. free-drug combination therapy.When theThis study suggested that single pill triple combination therapy was cost-effective in comparison with free combination therapy under a willingness to pay threshold of 50,000 when the strict adherence measurement criteria was applied.

Our study aimed to identify the correlation between the presenting FT4 values and FT4 values after the radioiodine therapy. Patients, after 10 mCi fixed dose radioiodine therapy for thyrotoxicosis were followed up at 03, 06 months intervals at Nuclear Medicine, Peradeniya. The details on base line clinical presentation, FT4 levels and the clinical status after the radioiodine therapy were collected using an interviewer administered questionnaire. Data was analysed using the SPSS version 25 by using Pearson’s correlation and independent sample t-test. There were 70.2% of Graves’ disease patients and 29.8% of toxic multi nodular goitre patients among the 57 patients consented for the follow up. The Pearson’s correlation showed a weak relationship between the FT4 value on diagnosis and the FT4 value after 03 months (r=0.475, P0.003) and a moderate relationship between the presenting FT4 value and the FT4 value before any intervention on or before 06 months after the radioiodine therapy (r=0.644, P

Background: Introduction: Total hip arthroplasty (THA) is a successful surgical procedure for reducing pain and improving physical function in osteoarthritis. It is one of the most effective orthopaedic procedures. Material and methods: Patients were eligible for the study if they were aged 18 years or older and were scheduled for total hip arthroplasty. Patients were ineligible if they were scheduled to undergo staged, bilateral hip arthroplasty were pregnant or breastfeeding, had active bleeding or a high risk of bleeding, or any disorder contraindicating the use of Rivaroxaban/enoxaparin that might necessitate enoxaparin dose adjustment. Results: Of the 52 patients enrolled in study, 52 patients were randomized to receive either Rivaroxaban (n=26) or enoxaparin (n=26). The baseline demographic characteristics of the two randomized treatment groups are well balanced as described in Table 1. The surgical characteristics are described in Table 2. Conclusion: Rivaroxaban, given as a once-daily 10 mg fixed dose 6–8 h postoperatively, is the first new oral anticoagulant to significantly reduce the incidence of venous thromboembolism after total knee arthroplasty, compared with enoxaparin 30 mg twice daily, starting 12–24 h postoperatively, without a significant difference in the risk of major or clinically relevant bleeding.

Objectives: Body weight is one of the factors affecting blood levels of 25-hydroxyvitamin D (25OHD). The aim of this study was to establish whether a vitamin D (vitD) weight-based dosing is more ap...

AIM To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9-39) in patients with post-bariatric hypoglycaemia (PBH). METHODS In this phase 2, multiple-ascending-dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending-dose levels of twice-daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses. RESULTS Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose-dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose

Iatrogenic manganese (Mn) neurotoxicity is a safety concern in neonates receiving parenteral nutrition (PN). Prior studies suggest Mn contamination of PN ingredients represents an unintended source of Mn delivery. In order to determine the relative contribution of unsourced Mn to total Mn exposure in neonatal PN, this study measured Mn concentrations in neonatal PN solutions using inductively coupled plasma mass spectrometry. Solutions prepared using a standard fixed dose neonatal multiple trace element product were compared with test solutions prepared using individual trace element ingredients not including Mn. The standard solutions (n = 6) contained a mean (SD) Mn concentration of 56.63 μg/L (0.94), compared with 6.04 μg/L (0.39) in the test solutions without added Mn (n = 6). This study suggests that neonatal PN contains significant quantities of Mn not intentionally added during PN preparation. Further studies are needed to identify individual ingredient sources of unintentional Mn, and the feasibility of Mn omission strategies.

Purpose The burden of hepatitis C virus infection is particularly high in Asian countries, and new treatments are urgently needed. The purpose of this study was to characterize the pharmacokinetics (PK) and safety of the fixed-dose combination tablet of elbasvir/grazoprevir in healthy Chinese participants. Patient and Methods In this Phase I, single-site, open-label, 3-period study in healthy Chinese adults, participants received a single tablet of elbasvir 50 mg/grazoprevir 100 mg, followed by blood sampling for up to 96 hrs (http://www.chinadrugtrials.org.cn/ CTR20160034; Protocol PN071). Participants then received 1 tablet daily for 10 days, followed by a minimum 10-day washout, after which participants received a single dose of 2 tablets (elbasvir 100 mg/grazoprevir 200 mg). Elbasvir and grazoprevir PK were assessed following single and multiple doses. Safety and tolerability were also evaluated. Results Twelve participants (50% male) were enrolled in and completed the study. Following single-dose oral administration of elbasvir 50 mg/grazoprevir 100 mg or elbasvir 100 mg/grazoprevir 200 mg, the median Tmax was 3-4 hrs and elimination half-life was 18 hrs (elbasvir) and 30 hrs (grazoprevir). Multiple-dose administration resulted in AUC0-24 accumulation ratios of 1.58 (elbasvir) and 2.35 (grazoprevir). Both elbasvir 50 mg/grazoprevir 100 mg and 100 mg/200 mg regimens were generally well tolerated. Conclusion Single-dose administration of elbasvir 50 mg/grazoprevir 100 mg or 100 mg/200 mg and once-daily administration of elbasvir 50 mg/grazoprevir 100 mg for 10 days has been adequately characterized, with PK values within the expected range, and was generally well tolerated in healthy Chinese male and female participants.

The home blood pressure control by a single-pill combination of cilnidipine and valsartan (HOPE-Combi) survey sought to evaluate the safety and efficacy of cilnidipine 10 mg/valsartan 80 mg single-pill combination (SPC of Cil/Val) treatment in patients with hypertension for over 12 months. Of 2622 subjects’ data; we analyzed 2572 cases for safety and 2372 cases for efficacy. Adverse drug reaction (ADR) incidence rate was 3.77% (97 of 2572 patients). The frequency of ADRs did not differ between patients aged P P : The SPC of Cil/Val was safe and effective in treating BP of hypertensive patients in real-world settings.

Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide‐type and thiazide‐like diuretics as first‐line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first‐line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide‐like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide‐type diuretics are more widely used than thiazide‐like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.

Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate (MF/IND) and mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY), both delivered via the Breezhaler® device, are approved for the maintenance treatment of asthma. Across these fixed-dose combinations, while the doses of bronchodilators remain the same, the nominal doses of mometasone furoate in micrograms differ. This article presents the steps followed in bridging the mometasone furoate doses at the corresponding dose strengths in the mometasone furoate formulation delivered via the Twisthaler® and mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulations delivered via the Breezhaler®. These were: (i) bridging the mometasone furoate doses in the Twisthaler® (previously approved) to mometasone furoate doses in the Breezhaler®; (ii) bridging the mometasone furoate doses in the Breezhaler® to mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation. Following this stepwise approach, it was determined that mometasone furoate 80 μg o.d. (medium-dose strength) and 160 μg o.d. (high-dose strength) in mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation provided comparable inhaled corticosteroid efficacy to mometasone furoate 160 μg o.d. (medium-dose strength) and 320 μg o.d. (high-dose strength) in the mometasone furoate/indacaterol acetate formulation, respectively. These doses were used in the PLATINUM Phase III clinical program that investigated the efficacy and safety of mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide combinations in patients with asthma.

BACKGROUND This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. METHODS Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any

We report four cases of ulcerated striae following misuse of fixed dose combinations creams containing clobetasol propionate with antifungal and antibacterial agents.

Introduction Challenges with personalised prophylaxis in haemophilia remain, including designing unique dosing schedules that require continual adjustments and monitoring using complex sampling procedures. Aim To assess long-term efficacy and pharmacokinetic outcomes with fixed-dose N8-GP prophylaxis. Methods Descriptive analyses were performed on data from the pathfinder 2 and pathfinder 5 trials of patients with severe haemophilia A. Bleed frequency and reoccurrence were assessed in relation to several clinical criteria of interest. Bleed risk relative to time since last dose was assessed using calculated annualised bleeding rate (ABR). Long-term ABR and mean factor VIII (FVIII) trough levels were assessed in patients who received consistent N8-GP prophylaxis every 4 days (Q4D). Results During pathfinder 2, 117/136 patients with study-drug exposure of ≥600 days experienced bleeding episodes; 8.6% of bleeds were reoccurring bleeds; bleed reoccurrence decreased over time. For patients who received consistent Q4D prophylaxis across the trial (n = 61), mean ABR decreased from 3.5 bleeds/year (Year 1) to 1.6 bleeds/year (Year 6); mean FVIII trough levels stabilised at approximately 5% (Year 6). Across patients who received prophylaxis at some point during pathfinder 2 (n = 177), 125/126 (99%) reoccurring bleeds were joint bleeds. For patients receiving Q4D prophylaxis, bleeding risk generally increased as the time since the last prophylaxis dose increased. A similar reduction in ABR and stabilisation of trough level was observed in pathfinder 5. Conclusion Long-term exposure (> 5 years) to fixed-dose N8-GP prophylaxis resulted in a protective haemostatic effect, with reduction in bleed frequency and reoccurrence, and stabilisation of FVIII trough level over time.

Aim: The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). Materials and methods: Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. Results: One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5–90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0–50.0 min with SC and 130.0–300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1–3 IV → cycles 4–6 SC: 77.5% → 72.5%; cycles 1–3 SC → cycles 4–6 IV: 77.5% → 63.8%). Conclusion: Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.