Niacin Extended-Release Therapy in Phase III Clinical Trials is Associated with Relatively Low Rates of Drug Discontinuation due to Flushing and Treatment-Related Adverse Events

Background and Objective

Niacin is a highly effective agent for increasing low high-density lipoprotein cholesterol (HDL-C) levels. It also has beneficial effects on key pro-atherogenic lipoprotein parameters. However, the side effect of flushing can challenge patient adherence to treatment. In this study, we pooled safety data from available trials of at least 16 weeks’ duration to evaluate the impact of flushing on patient adherence to niacin extended-release (NER) therapy.

Methods

Data were pooled from eight NER studies (administered as NER with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40mg/day [NER/S], or lovastatin 20 or 40 mg/day [NER/L]) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events.

Results

While 66.6% of patients experienced flushing, only 5.2% of patients discontinued treatment due to flushing. Of the total number of patients treated with NER (n = 307), NER/S (n = 912), or NER/L (n = 928), 34 (11%), 105 (11%), and 127 (14%) patients discontinued due to any treatment-related adverse event, respectively, while 14 (5%), 43 (5%), and 55 (6%) discontinued due to flushing. Discontinuation for flushing did not differ with regard to maximum dose, or to the presence or type of statin combined with NER.

Conclusion

Although flushing was common with NER treatment, discontinuation due to flushing occurred in only 5–6% of patients in this pooled analysis. This could be due to several factors, including the fact that all patients in the NER trials were educated about flushing and its management. Translation of methodology employed in these trials into clinical practice may improve long-term adherence to NER therapy, which would enhance the therapeutic benefit of NER for reducing cardiovascular risk.     

Serum NT-proBNP concentrations in the early phase do not predict the severity of systolic or diastolic left ventricular dysfunction among patients with ST-elevation acute myocardial infarction

The cohort included 55 consecutive patients with first ST elevation acute myocardial infarction (STEAMI) who underwent reperfusion. Blood samples were drawn for N-terminal pro B-type natriuretic peptide (NT-proBNP), highly-sensitive C-reactive protein (hs-CRP), creatinine kinase (CK), cardiac troponin l (cTnl), and white blood cell (WBC) count within 24 hours of admission. Transthoracic echocardiography, performed within the same time frame, assessed left ventricular (LV) systolic function, as well as diastolic function. Variables significantly associated with poor systolic LV dysfunction were hs-CRP, peak CK, cTnl, and WBC. There was no significant correlation between NT-proBNP and systolic function early after STEAMI (p=0.49). Among patients with diastolic dysfunction, there was no significant correlation between NT-proBNP levels and peak mitral E-wave velocity to peak initial A-wave velocity (E/A ratio) (r =0.19, p=0.18) or E-wave deceleration time (r =0.22, p=0.15). Thus, NT-proBNP levels in the early phase after STEAMI were not indicative of systolic or diastolic function.     

Reduction in ventilator-induced lung injury improves outcome in congenital diaphragmatic hernia?

The purpose of this historical study was to compare the outcome for two treatment strategies, for neonates with congenital diaphragmatic hernia (CDH). The records of 65 infants born between 1991 and 2005 with CDH from a single tertiary care perinatal centre in the United Kingdom were retrospectively reviewed. Conventional mechanical ventilation (CMV) and systemic vasodilators were used from 1991 to 1995 (era 1). High frequency oscillatory ventilation (HFOV) and nitric oxide (NO) were used between 1996 and 2005 (era 2). Main outcome measures were survival and incidence of chronic lung disease. The results showed that the survival rate was 38% (8/21) in era 1 and 73% (32/44) in era 2, 95% CI for difference −59 to −10%. The incidence of chronic lung disease in survivors was 45% (5/11) in era 1 and 30% (9/30) in era 2, 95% CI for difference −18 to 49%. These data show significantly improved survival with elective use of HFOV and NO compared to CMV and systemic vasodilators. The survival results for CDH at St George’s Hospital are comparable to those published from other institutions. The results may reflect a reduction in ventilator-induced lung injury with HFOV compared to CMV.     

In vitro blood culture bottle inoculation of whole blood with clinically relevant antibiotic concentrations: a word of caution

European Journal of Clinical Microbiology & Infectious Diseases -     

The management of drooling problems in children with neurological dysfunction: a review and case report

Drooling in children with neurological dysfunction indicates neurogenic failure to coordinate the muscles of the tongue, soft palate, and face which act in the first stage of swallowing. This causes excessive pooling of saliva in the anterior part of the mouth and consequent overspill. Treatment for drooling includes behavioral, pharmacological, and surgical modalities. Correcting a malocclusion has also been reported to help eliminate drooling. This paper describes the treatment of a child with neurofibromatosis, psychomotor, developmental, and neurologic retardation, and difficulty with speech. The patient was referred to our clinic to correct his drooling. Simple orthodontic treatment succeeded in eliminating the drooling and Improving his speech .     

Distraction With Virtual Reality Goggles in Paediatric Dental Treatment: A Randomised Controlled Trial

AimThe aim of this study was to examine whether screening content through virtual reality (VR) goggles can diminish pain perception during local anaesthesia administered using the inferior alveolar nerve block technique and rubber dam placement in routine paediatric dental treatment.Materials and methodsThis is a crossover study of healthy 4- to 12-year-old children who were scheduled to receive local anaesthesia administered using the inferior alveolar nerve block technique and rubber dam placement in 2 visits. The participants were randomly assigned to undergo 1 treatment performed with Oculus GO VR goggles and the other treatment without. Pain was evaluated using the Wong-Baker FACES Pain Rating Scale and the Modified Behavioral Pain Scale (MBPS).ResultsThe study group included 29 children with a mean age of 8.29 years (SD, 1.96). Whilst administering local anaesthesia, no significant difference was observed in the Wong-Baker FACES Pain Rating Scale and in MBPS movements between visits with and without the VR goggles. However, significantly lower pain perception was observed in the other parameters of MBPS when using the VR goggles: Face (P = .007) and Cry (P = .046). During placement of a rubber dam, significantly less pain was reported by the patients (P = .005) and observed by the assessor (Face [P = .005], Cry [P = .029], and Movement [P = 0.028]) when the VR goggles were used.ConclusionsVR can decrease pain perception during rubber dam placement in children, but it has limited benefit during administration of local anaesthesia.     

Fish Oil as an Adjuvant in the Treatment of Hypertension

Study Objective . To evaluate the effects of ω-3 fatty acids on blood pressure control and lipid levels. Design . Double-blind, placebo-controlled, randomized study. Setting . Veterans Affairs Medical Center teaching hospital. Patients . Twenty-one men whose blood pressure was not optimally controlled with antihypertensive agents, who met the inclusion criteria. Interventions. Patients were randomized to receive either fish oil (4.5 g ω-3 fatty acids/day) or placebo. Measurements and Main Results . Blood pressure readings were taken at baseline, and 4 and 8 weeks. Sitting systolic and diastolic blood pressures were significantly reduced in the fish oil group at both week 4 (148/97 to 132/90, p<0.05) and week 8 (148/97 to 134/91, p<0.05). Sitting diastolic blood pressure was significantly reduced in the placebo group at week 8 (94 to 88, p<0.05). There was no difference in percentage change of sitting systolic and diastolic pressures at week 8 comparing the placebo group (−6.4% and −6.3%, respectively) and the fish oil group (−8.8% and −6.6%, respectively). Triglyceride levels (−40.9%, p<0.05) and platelet counts (−8.7%, p<0.05) were significantly reduced at 4 weeks, and low-density lipoprotein (LDL) cholesterol levels were significantly increased both at 4 and 8 weeks (13.5% and 19.1%, respectively) in the fish oil group. Conclusion . Adjunctive fish oil supplementation did not substantially augment blood pressure lowering in treated hypertensive men with suboptimally controlled blood pressure. Effects on plasma lipid values were mixed, with an increase in LDL cholesterol and a decrease in plasma triglyceride levels.