Journal of Drug Assessment最新文献

In critically ill patients, sleep is generally interrupted. Some factors that lead to such sleep interruption include the intensive care unit (ICU) circumstance, primary medical disease itself, mental stress, and impacts of many drugs and other managements utilized to treat ICU patients. Another illness that may cause profound daytime somnolence is narcolepsy. Modafinil, methylphenidate and amphetamines are used as stimulants to treat symptoms, such as extreme daytime sleepiness, cataplexy and nocturnal sleep disruption. Such stimulants can increase awareness, improve perception and thinking, as well as assist in keeping people awake. The exact mechanism of action of modafinil is unclear. In vitro studies have demonstrated that binding of modafinil to the dopamine reuptake pump can prevent the reuptake of dopamine, resulting in a boost in extracellular dopamine. Modafinil is a racemic compound containing l and d isomers. Peak plasma concentrations of the drug occur at 2-4 h after administration; therefore, the absorption of modafinil is considered fast. Modafinil is properly distributed in tissues by binding to plasma proteins moderately. Despite the likely role of modafinil in improving cognition and arousal in critically ill patients, the available data on the use of modafinil in the ICU setting is limited. The aim of the study was to review the novel usage of modafinil for alleviation of fatigue, excessive daytime somnolence (EDS), and/or depression in critically ill patients.

Background: The aim of management of acute low back pain is to alleviate the pain quickly and improve functional ability. Non-steroidal anti-inflammatory drugs are the first line of treatment. The challenge lies in deciding which NSAIDs will provide greater symptomatic relief, while also being cost-effective. Objective: To compare the effectiveness of aceclofenac and etoricoxib in the management of acute low back pain. Methods: This prospective, open label, observational study was conducted at a tertiary care hospital. Patients over 18 years of age and presenting with low back pain of less than 6 weeks duration were enrolled in the study. Fifty patients with non-specific low back pain were randomized into two groups: Group A received aceclofenac (2 mg/kg) twice a day and Group B received etoricoxib (1 mg/kg) twice a day for 1 week. The Numerical Rating Scale (NRS) and Oswestry Low Back Disability Index (ODI) determined the clinically meaningful outcomes. Results: The decrease in pain intensity in Group A was 52.27%, while in Group B it was 62.53%. However, the decrease in pain scores between the groups was not statistically significant (p = .3795). Improvement in functional ability in Group A and Group B was 57.01% and 61.48%, respectively. However, this improvement between the groups was not statistically significant (p > .999) at the end of 1 week. The average cost-effectiveness ratio indicated that etoricoxib was the dominant treatment over aceclofenac. Therefore, etoricoxib was found to be the cost-effective option for short-term pain relief in acute low back pain for 1 week. Conclusion: Both aceclofenac and etoricoxib were clinically effective in reducing the pain intensity and in improving functional ability. However, etoricoxib was found to be the cost-effective intervention.

Purpose: To describe a standardized protocol of the dexamethasone intravitreal (DEX) implant Ozurdex (Allergan, Dublin, Ireland) performed in a controlled environment surgical cabin (CESC). Methods: Retrospective and observational study conducted on patients who underwent a DEX implant between May 2011 and June 2019, in a third level University Hospital. The controlled environment surgical cabin (ArcSterile, Imex, Valencia, Spain) used in this study was the MB 20 (2 m width, 1.60 m depth, and 2 m height) with an uninterrupted power system (ARSSAI1) to keep the cabin working for 20 min. The cabin was used in the open mode. A standardized protocol of intravitreal injections in controlled environment surgical cabin was designed. Results: From May 2011 to February 2015, a total of 454 DEX implants were performed in the operating room, whereas from March 2015 to June 2019, 1054 DEX devices were implanted using the CESC. The mean number of DEX implants/per week was significantly lower in the operating room than in the CESC [2.3 (2.1 to 2.5) versus 3.8 (3.6 to 4.1), mean difference 1.5 (1.2 to 1.8), p < 0.0001]. The incidence of endophthalmitis was similar in the two populations, 0/454 (0.0%; 95% CI 0.0 to 0.81%) and 0/1054 (0.0%; 95% CI 0.0 to 0.35%) in the operating room and in the CESC, respectively. Conclusions: The CESC may be a good alternative to the conventional operating room for the administration of the intravitreal DEX implant.

Objectives: The current research work has potential for delivery of fluvoxamine moiety in bio-nanosuspension mode for the effective treatment of depression. Depression is a mood disorder characterized by persistently low mood and a feeling of sadness and loss of interest. Methods: The fluvoxamine loaded bio-nanosuspension was prepared using novel bio-retardant isolated from fruit pulp of Cucumis sativa by a novel method with different ratios (1:1, 1:2, 1:3, 1:4, 1:5) and the same ratios with standard polymer eudragit L-100. The bio-nanosuspensions were evaluated for pH stability studies, percentage entrapment efficacy, in vitro drug release, particle size, polydispersity index, zeta potential, and stability studies. Results: The bio-nanosuspension was subjected to the best formulation based on comparison of above mentioned evaluation parameters, and the Fc1 (1:1) formulation was found to be the best formulation. Cucumis sativa provided excellent stability for the formulation, and the resulting particle size was found to be 194 nm. The bio-nanosuspension had a Polydispersity Index (PDI) of 0.13 with zeta potential of -17.9 mV. Conclusion: The fluvoxamine loaded bio-nanosuspension using Cucumis sativa was found to be nontoxic and compatible with drug delivery systems for treatment of depression. This was the first report in which Cucumis sativa as a bioretardant demonstrated greater retardability over the standard polymer eudragit-100.

Objective: The purpose of this study was to investigate the potential ability of autologous conditioned serum (ACS) to decrease pain and improve joint functionality in patients affected by knee osteoarthritis (OA). Methods: Fifteen patients with clinical and radiological signs of OA of the knee were recruited for this study. Each patient received 4 injections of ACS (Orthokine; orthogen, Dusseldorf, Germany) at the site of OA once per week for 4 weeks. Clinical and functional evaluation was performed using the VAS scale for pain, WOMAC scale and KSS functional and clinical scores before the first injection, at one week, at two weeks, at three weeks, at one month and at six months. Statistical analysis was done with the Wilcoxon Signed-Rank Test. Results: Our results show an improvement of all the evaluation scales at 6 months follow-up. Particularly, VAS scales among all patients decreased by 35.8% (p = .00148), KSS functional scores improved by 38.2% (p = .00148), KSS clinical scores improved by 28.9% (p = .00236) and WOMAC scores were reduced by 19.8% (p = .00188). Few adverse effects were observed in our sample. The most common complaint was pain and swelling in the subsequent days after performing the intra-articular injection. Only one patient reported rigidity following the injection of the ACS. Conclusion: Our results, in conjunction with preexisting studies in the medical literature regarding ACS, demonstrate the viability of this therapy for the treatment of knee OA, showing positive influence on pain and joint function without significant adverse effects.

Background: To enhance the outcome in patients with invasive candidiasis, initiation of an efficient antifungal treatment in a suitable dosage is necessary. Echinocandins (e.g. caspofungin) inhibit the enzyme β(1,3)-D-glucan synthase of the fungal cell wall. Compared to azoles and other antifungal agents, echinocandins have lower adverse effects and toxicity in humans. Echinocandins are available in injectable (intravenous) form. Methods: In this study, to identify the novel oral drug-like compounds that affect the fungal cell wall, downloaded oral drug-like compounds from the ZINC database were processed with a virtual screening procedure. The docking free energies were calculated and compared with the known inhibitor caspofungin. Four molecules were selected as the most potent ligands and subjected to hydrogen bonds analysis. Results: Considering the hydrogen bond analysis, two compounds (ZINC71336662 and ZINC40910772) were predicted to better interact with the active site of β(1,3)-D-glucan synthase compared with caspofungin. Conclusion: The introduced compound in this study may be valuable to analyze experimentally as a novel oral drug candidate targeting fungal cell walls.

Objective: To assess the consistency between current recommendations that women of body weight (BW) or body mass index (BMI) above a defined threshold should use a double dose of levonorgestrel (LNG) for emergency contraception (EC) and observed frequency of pregnancy in historic studies of single-dose LNG for EC. Methods: We applied double dose recommendation criteria to individual participant level data from three historic studies of the WHO's Human Reproductive Program to categorize subjects into single dose-recommended (SDR) and double dose-recommended (DDR) groups and compared the latter to the former using pregnancy risk ratios (RR). Results: A total of 5859 subjects with 59 pregnancies made up the full dataset. Depending on the recommendation source (USA or UK) and inclusion or exclusion of heavy outlier data, DDR criteria were satisfied by 3.7% to 18.9% of subjects. Pregnancy proportions were mostly lower in DDR than in SDR subjects, with risk ratio estimates ranging from zero to 1.17, exceeding unity only when the USA criterion was used with outliers included. DDR subjects had a significantly lower relative frequency of pregnancy than SDR subjects when the UK criteria were used and outliers excluded (RR = 0.17 [95% CI: 0.04; 0.70], p = .0024). Conclusions: Our findings are consistent with the notion that there is no real loss of pregnancy control with single-dose LNG-EC in high-BMI and/or high-BW users, and today's double dose recommendations were prematurely issued and remain questionable.

Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNβ) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNβ are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.

Objectives: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha₂-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. Methods: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. Results: Study 1 (N = 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1-7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N = 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1-5 for lofexidine 2.16 mg/day and placebo, respectively (p = .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. Conclusion: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis. ClinicalTrials.gov identifier: Study 1, NCT01863186; Study 2 NCT00235729. URL: https://clinicaltrials.gov/.

Background: There are limited data on the real-world evidence of Humalog 200 units/ml KwikPen (U-200) insulin. We assessed the use of U-200 insulin in UK routine clinical practice to provide information on clinical characteristics, treatment satisfaction and short-term clinical outcomes. Methods: Nine patients with type 2 diabetes who initiated U-200 in secondary care and a further 12 identified from primary care electronic database were enrolled. A treatment satisfaction questionnaire was administered to the 19 secondary care patients. Follow-up data on clinical parameters were collected at 3 and 6 months following initial U-200 insulin administration and the data were used to assess changes in clinical outcomes from baseline. Results: Secondary care patients had a mean age 60 ± 11 years, mean HbA1c of 8.6% ± 1.3% and a mean BMI of 39.7 ± 5.3 kg/m² at baseline. Primary care database patients had a mean age 57 ± 13 years, mean HbA1c 10.3% ± 1.7 and a mean BMI 42.3 ± 3.8 kg/m². The nine participants' responses to the questionnaire suggested a high preference for U-200 over a previous mealtime insulin pen (PMIP). On average, the patients agreed that U-200 was quicker to inject, had a better controlled home blood glucose reading and less discomfort at the injection site compared to a PMIP. Patients were willing to continue with their U-200 treatment. No significant HbA1c reduction was observed at 3 months in the secondary care group (-0.5%), but marked significant reduction in HbA1c was seen at 3 months in the primary care dataset to (-2.8%; p < .0004). There was also some suggestion of weight loss in both the secondary and primary care groups. Conclusion: Humalog U-200 insulin users were comprised mainly of older patients with diabetes complications and high HbA1c levels at the time of U-200 initiation. Overall, U-200 improved patients' satisfaction with diabetes treatment and short-term metabolic outcomes.