Search

Background: There are many paediatric specific challenges such as lack of age-appropriate dosage forms, inability of young children to swallow tablets and capsules and poor acceptability, during administration of oral dosage forms of medications to children. Parents adopt various methods which they consider best to circumvent this problem. The objective of this study was to describe the administration practice by parents when giving oral dosage forms of medications to children. Methods: A descriptive cross-sectional study was conducted to assess the administration practice of 1800 oral dosage forms of medications administered to children under the age of 12 years using validated indicators. A pre-tested interviewer-administered questionnaire given to parents or caregivers was used to collect the necessary data. The data were analysed using descriptive statistics. Results: Data from 1800 oral dosage forms was obtained from 663 children. Of the 1287 solid dosage forms, almost one-third were manipulated by parents at the time of giving the medications to children. They were crushed and dissolved in water given to children. In about 17% of instances safety of water was questionable. In 92% of instances, measuring device was found to be inappropriate. Conclusion: Administration of oral dosage forms of medications to children is far from ideal and hinders successful use of medications in children. [ABSTRACT FROM AUTHOR]

Prior to gene therapy, the patient received iron chelation treatment with deferasirox and deferoxamine and had an intact spleen, with good adherence to standard-of-care treatment. This Greek patient was one of the oldest patients treated in gene therapy trials for -thalassaemia. Keywords: gene therapy; thalassaemia; haemoglobinopathies EN gene therapy thalassaemia haemoglobinopathies 1401 1404 4 03/22/22 20220315 NES 220315 Transfusion-dependent -thalassaemia (TDT) is a severe, rare genetic disease where impaired production of the -globin chain of adult haemoglobin (Hb) results in a deficiency of functional red blood cells (RBCs), bone marrow expansion and ineffective erythropoiesis, chronic anaemia and haemolysis, leading to serious complications, reduced quality of life and a shortened lifespan.1,2 Patients require lifelong supportive care with chronic blood transfusions and iron chelation that are burdensome and many patients fail to comply with the standard of care.1-4 Even under optimal monitoring, transfusion and iron chelation treatment, patients with TDT experience a high proportion of disease- and treatment-related complications.5 Allogeneic haematopoietic stem cell (HSC) transplantation is potentially curative, but is limited by donor availability and patient age, and associated with transplant-related complications.1,2,6 Gene therapy with betibeglogene autotemcel (beti-cel; LentiGlobin for -thalassaemia) showed positive results in patients with TDT and SP + sp genotypes in phase I-II studies7; however, six of nine patients with severe -thalassaemia genotypes (i.e. SP 0 sp / SP 0 sp or homozygous IVS1-110 mutation) did not achieve transfusion independence (TI). [Extracted from the article]

Background: In general, safety data following exposure to drugs in the first trimester of pregnancy are scarce. More specifically, data on the safety of artemisinin-based combination therapy (ACT) in pregnancy still remain limited. Therefore, pregnant women from Choma, Zambia, who were exposed to artemether-lumefantrine (AL) for the treatment of uncomplicated malaria were followed up and evaluated in a prospective cohort study. This report assessed the longitudinal safety outcomes of the pregnant women inadvertently exposed during the first trimester. Methods: Participants were classified based on the drug used to treat their most recent malaria episode: artemether-lumefantrine (AL) versus sulphadoxine-pyrimethamine (SP) and/or quinine. All enrolled women were followed up until six weeks post-delivery and the live births for 12 months. Results: There were 294 first trimester exposures in the observational cohort (pregnant women: AL = 150, AL and SP = 9 and SP and/or quinine = 135). Similar rates of perinatal mortality (stillbirths and neonatal deaths) were observed for each treatment arm (AL 4.4%, SP and/or quinine 3.9%). At delivery (newborns: AL = 135, AL and SP = 7 and SP and/or quinine = 129), the gestational age (measured using the Dubowitz total scores), length and head circumference of the newborns were similar between the two arms. Low birth weights were reported in 10.2% (95% CI 6.0, 16.6) and 6.7% (95% CI 3.4, 12.6) of newborns in the AL and SP and/or quinine arms, respectively. Overall development (including neurodevelopmental parameters) was similar between the two arms, both at 14 weeks and 12 months of age. Conclusion: Exposure to AL and SP in the first trimester was not associated with particular safety risks such as perinatal mortality, preterm deliveries or low birth weights. Such outcomes as well as infant neurodevelopmental parameters up to 12 months were similar between the two arms. These findings add to the body of data suggesting that randomized clinical trials could now be the way forward to assess safety and efficacy of ACT in the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Treatment options for adults with attention deficit hyperactivity disorder (ADHD) are limited. The study was conducted to confirm the clinically effective and safe dose of methylphenidate hydrochloride modified-release (MPH-LA) in adults with ADHD and evaluate the maintenance of effect of MPH-LA. Methods: The study consisted of three treatment phases. The double-blind dose-confirmation phase: 9-week double-blind period (3-week titration period, 6-week fixed dose) with randomization to MPH-LA 40, 60, or 80 mg/day or placebo. The real- life dose-optimization phase: a 5-week re-titration period to optimal dose; and the double- blind maintenance of effect phase, a 6-month double-blind randomized placebo-controlled maintenance of effect phase. The three co-primary endpoints were change in Diagnostic and Statistical Manual of Mental Disorders-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores from baseline to end of 9-week confirmation phase and the percentage of treatment failures during the 6-month maintenance of effect phase. Results: 725 of 863 screened patients were randomized to 40 ( N = 181), 60 ( N = 182), or 80 mg ( N = 181) MPH-LA or placebo ( N = 181), and 584 (80.6%) completed. 489 (83.7%) of completers were re-randomized to the double-blinded maintenance of effect phase and 235 (48.1%) of them completed. Improvement from baseline in DSM-IV ADHD RS ( P < 0.0001 for all comparisons) and SDS (40 mg, P = 0.0003; 60 mg, P = 0.0176; 80 mg, P < 0.0001) total scores was significantly greater vs. placebo for all MPH-LA doses. Treatment failure rate was significantly lower with MPH-LA (21.3%) versus placebo (49.6%) during the 6-month maintenance of effect phase. Safety profile was consistent with the profile for MPH-LA in children; percentage of serious adverse events was comparable between all MPH-LA arms (1.3%) and placebo (1.5%), while percentage of adverse events was higher in MPH-LA arms. Conclusion: MPH-LA provided and maintained significant symptomatic and functional improvement in adult ADHD patients. [ABSTRACT FROM AUTHOR]

Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively. Results: Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P,0.0001), indicating improvement in health-related quality of life. Conclusion: ExtaviJect 30G was convenient to use and was associated with high levels of compliance. [ABSTRACT FROM AUTHOR]

Background: The ExtaviPro™ 30G autoinjector has been developed for self-administration of interferon beta-1b (Extavia®), which is used as a first-line, parenteral, disease-modifying therapy in multiple sclerosis (MS). The aim of this survey was to investigate patients' perceptions of the importance of different general attributes of autoinjectors, and patient preferences when comparing the ExtaviPro™ 30G and Betacomfort® autoinjectors. Method: The survey was conducted in France, Germany, Italy, and the USA in patients with relapsing-remitting MS who had been using an autoinjector for at least 1 year. Participants examined the ExtaviPro™ 30G and Betacomfort® devices, viewed fact sheets, and watched a video of these autoinjectors in use, then scored nine prespecified attributes of autoinjectors in terms of importance on a scale of 1-7 (1 = not at all important; 7 = extremely important). They then indicated which device they preferred, both overall and by individual attribute. Results: Among the 201 participants who completed the survey, being reliable to use was considered the most important general attribute of autoinjectors, followed by attributes associated with convenience (ease of operation, one-handed injection, ease of reach of injection sites, ergonomic shape). For each of the nine attributes, a significantly higher proportion of participants (74%-94% by attribute; P, 0.05 for each) preferred ExtaviPro™ 30G to the Betacomfort® autoinjector, and 173 (86%) participants indicated that they preferred ExtaviPro™ 30G overall (P, 0.05). Conclusion: The results of this survey suggest that patients with MS rate reliability and convenience as the most important general attributes of autoinjectors, and are more likely to prefer ExtaviPro™ 30G to the Betacomfort® autoinjector for routine self-administration of interferon beta-1b. [ABSTRACT FROM AUTHOR]

Background: In malaria-endemic countries, large proportions of infected individuals are asymptomatic, constituting a reservoir of parasites for infection of newly hatched mosquitoes. This study evaluated the impact of screening and treatment of asymptomatic carriers of Plasmodium falciparum. Methods: Eighteen villages were randomized (1:1) to study arms and inhabitants participated in four community screening campaigns: three before the rainy season ~1 month apart, and the fourth after the rains at ~12 months. On day 1 of campaigns 1-3, asymptomatic carriers in the intervention arm were identified by rapid diagnostic test and treated with artemether-lumefantrine. Outcomes were symptomatic malaria with parasite density >5,000/µL per person-year in children <5 years and change in haemoglobin between days 1 and 28 of campaign 1. Results: At 12 months, the number of symptomatic malaria episodes with a parasite density >5,000/µL per personyear in children <5 years was not significantly different between arms (1.69 vs 1.60, p = 0.3482). Mean haemoglobin change in asymptomatic carriers during campaign 1 was greater in the intervention vs control arm (+0.53 g/dL vs -0.21 g/dL, p <0.0001). ANCOVA demonstrated that mean asymptomatic carriage at the cluster level was lower in the intervention vs control arm at day 1 of campaigns 2 (5.0% vs 34.9%, p <0.0001) and 3 (3.5% vs 31.5%, p <0.0001), but showed only a small difference at day 1 of campaign 4 (34.6% vs 37.6%, p = 0.2982). Mean gametocyte carriage was lower in the intervention vs control arm at day 1 of campaigns 2 and 3 (0.7% vs 5.4%, p <0.0001; 0.5% vs 5.8%, p <0.0001), but was similar at day 1 of campaign 4 (4.9% vs 5.1%, p = 0.7208). Conclusions: Systematic screening and treatment of asymptomatic carriers at the community level did not reduce clinical malaria incidence in the subsequent transmission season, indicating greater levels of parasite clearance are required to achieve a sustained impact in this setting. [ABSTRACT FROM AUTHOR]

Objectives Gouty arthritis patients for whom non- steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0 100 mm visual analogue scale and time to first new flare. Methods Two 12-week randomised, multicentre, active- controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). Results 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p=0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p=0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p=0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count. Conclusion Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis. [ABSTRACT FROM AUTHOR]

The article explores the available data on the safety and efficacy of artemether-lumefantrine (AL) against uncomplicated Plasmodium falciparum malaria during pregnancy. It mentions that 16 publications with reports of artemether in pregnancy are identified from 1989 to October 2011. It notes that few reports are available on the safety of AL in the first trimester. It also emphasizes the need for further information on the safety and efficacy of using AL in the second and third trimesters.

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, doseranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4χ4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ⩾50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p⩽0.0083), and the percentage of patients experiencing ⩾1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ⩾1 flare for canakinumab doses ⩾50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p⩽0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ⩾50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. [ABSTRACT FROM AUTHOR]

The article presents information on a study that investigated the efficacy and safety of canakinumab in patients with rheumatoid arthritis (RA). The patients were undergoing therapy with doses of methotrexate. The study found that the addition of canakinumab improved therapeutic responses among patients despite treatment with methotrexate.

Aims: To examine whether the blood pressure (BP) profiles of lumiracoxib and high-dose ibuprofen differed in patients treated with different classes of antihypertensive medications. Methods: A 4-week, multicentre, randomised, double-blind study has compared the effects of lumiracoxib 100 mg once daily (od) ( n = 394) and ibuprofen 600 mg three times daily (tid) ( n = 393) on ambulatory BP in osteoarthritis (OA) patients with controlled hypertension. Here, we present subgroup analyses for patients receiving different antihypertensive classes. The primary outcome was a comparison of the change in 24-h mean systolic ambulatory BP (MSABP) from baseline to week 4. Patients receiving angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) represented the largest subgroups receiving antihypertensive monotherapy. Results: For patients receiving an ARB monotherapy, the least squares mean (LSM) 24-h MSABP at week 4 fell with lumiracoxib 100 mg od and increased with ibuprofen 600 mg tid, creating an estimated treatment difference of 8.1 mmHg in favour of lumiracoxib (p < 0.001). For patients receiving an ACEI and a beta-blocker monotherapy, the estimated treatment difference was 8.2 mmHg (p < 0.001) and 5.8 mmHg (p = 0.002) in favour of lumiracoxib respectively. These treatment differences were greater than observed in the overall population (5.0 mmHg in favour of lumiracoxib). In patients receiving diuretics or calcium channel blockers, treatment differences in MSABP were smaller and not statistically significant, although they remained in favour of lumiracoxib. Conclusion: Lumiracoxib 100 mg od resulted in less destabilisation of BP than high-dose ibuprofen 600 mg tid, and this effect was the greatest in subgroups treated with drugs blocking the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least-squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P <.0001) and +0.43 with lumiracoxib compared with +1.80 mm Hg with naproxen (P <.0001). In conclusion, the use of lumiracoxib and traditional NSAIDs results in differing BP changes; these might be of clinical relevance. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are established as treatment for managing pain associated with primary dysmenorrhea. However, the efficacy and tolerability of lumiracoxib 200 mg once daily (q.d.) has not previously been examined in primary dysmenorrhea. Methods: Two randomized, multicenter, double-blind, placebo-controlled, crossover studies of similar design have assessed the efficacy and tolerability of two regimens of lumiracoxib compared with placebo (Study 1) or naproxen and placebo (Study 2) in women (aged 18–45 years) with moderate to severe primary dysmenorrhea. In Study 1 ( n = 132), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose (p.r.n.) on day 1, or placebo. In Study 2 ( n = 144), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose p.r.n. on day 1, naproxen 500 mg twice daily (b.i.d.), or placebo. Patients recorded study medication use, efficacy assessments, and rescue medication use. Results: The primary efficacy variable, summed (time-weighted) pain intensity difference (categorical scale) over the first 8 hours (SPID-8), was similar between all active treatments (e.g., p = 0.939 for naproxen 500 mg b.i.d. vs. lumiracoxib 200 mg q.d. in Study 2), and all active treatments were superior to placebo ( p < 0.001). Median time-to-onset of analgesia was similar between lumiracoxib 200 mg q.d. and naproxen 500 mg b.i.d. Similar trends were observed for all other secondary efficacy variables. All treatments were well tolerated. Conclusions: Short-term administration of lumiracoxib 200 mg q.d. is effective and well tolerated and provides an alternative treatment option for the management of moderate to severe pain associated with primary dysmenorrhea. [ABSTRACT FROM AUTHOR]

Background: Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions. Methods: This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (n = 154) or rofecoxib 25 mg od (n = 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs. Results: Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (p < 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups. Conclusion: Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib. Trial registration number -: NCT00637949 [ABSTRACT FROM AUTHOR]

Objectives. To demonstrate non-inferiority of lumiracoxib 400 mg once daily (o.d.) compared with indomethacin 50 mg three times daily (t.i.d.) in the treatment of acute gout, and to compare the safety and tolerability of these treatments. [ABSTRACT FROM PUBLISHER]

Lifespan treatment in transfusion-dependent β-thalassemia (TDT) is expected to impact quality of life. This study aimed at evaluating health-related quality of life (HRQoL), well-being, and the burden of TDT on Italian patients. Patients (≥14 years) were invited to complete a cross-sectional, online volunteer survey. HRQoL was measured by the 36-item short-form health survey (SF-36) and wellbeing was measured by the Italian version of the Psychological General-Well-Being-Index (PGWBI). A total of 105/167 completed questionnaires were analyzed (46% males; median age 44, (IQR = 11)). Patients reported lower HRQoL compared with the general population in all SF-36 domains (except for emotional well-being (p = 0.7024) and role limitations due to emotional problems (p = 0.1389)). PGWBI domains general health and vitality and the total PGWBI score were all significantly lower (p = 0.0001) compared with the general population. On average, patients spent 16.62 h/month engaged in care activities that were additional to the time required for completing transfusions. Of the 16.62 h/month, 11.7 h/month were required for therapy management and 4.92 h/month for family management. This study found lower HRQoL and well-being in physical and psychological domains compared with the general population. Further, patients were found to have a high perceived burden of disease. [ABSTRACT FROM AUTHOR]