Lars Småbrekke

Severe Apnea in an Infant Exposed to Lamotrigine in Breast Milk

Objective: To report a case of severe apnea in an infant exposed to lamotrigine through breast-feeding. Case Summary: A 16-day-old infant developed several mild episodes of apnea that culminated in a severe cyanotic episode requiring resuscitation. A thorough examination at the hospital gave no evidence of underlying diseases that could explain the reaction. The mother had used lamotrigine in increasing doses throughout pregnancy, and at the time of the apneic episodes, she used 850 mg/day. The infant was fully breast-fed, and the neonatal lamotrigine serum concentration was 4.87 μg/mL at the time of admission. Breast-feeding was terminated, and the infant fully recovered. Discussion: Although there are several reports on extensive passage of lamotrigine into breast milk, this is the first published report of a serious adverse reaction in a breast-fed infant. Lamotrigine clearance increases throughout pregnancy, and maternal dose increases are often necessary to maintain therapeutic effect. After delivery, clearance rapidly returns to preconception levels, enhancing the risk of adverse reactions in both mothers and breast-fed infants if the dose is not sufficiently reduced. In this case, the dose was slowly reduced after delivery, and the maternal lamotrigine serum concentration more than doubled in the week before the neonatal apneic episodes. A high lamotrigine concentration was detected in the breast milk, and the neonatal lamotrigine serum concentration was in the upper therapeutic range. The neonatal lamotrigine elimination half-life was approximately twice that seen in adults. The Naranjo probability scale indicated a probable relationship between apnea and exposure to lamotrigine through breast-feeding in this infant. Conclusions: Infants can be exposed to clinically relevant doses of lamotrigine through breast-feeding. Individual risk/benefit assessment is important, and close monitoring of both mother and child is advisable, especially during the first 3 weeks postpartum.

Educational intervention for parents and healthcare providers leads to reduced antibiotic use in acute otitis media.

We used a controlled before-and-after design with the aims of reducing both the total consumption of antibiotics and the use of broad-spectrum antibiotics against acute otitis media (AOM), and to study to what extent prescriptions for antibiotics against AOM were dispensed. Information on evidence-based treatment of uncomplicated AOM was provided to doctors and nurses, and written guidelines were implemented. Pamphlets and oral information concerning symptomatic treatment and the limited effect of antibiotic use in AOM were given to parents. Eligible patients were 819 children aged 1-15 y. The proportion of patients receiving a prescription for antibiotics was reduced from 90% at baseline to 74% during the study period. The proportion of prescriptions for penicillin V increased from 72% at baseline to 85% during the study period. There were no significant changes at the control site. The proportion of dispensed prescriptions was 70% both at baseline and during the study period. Educational efforts reduced the total consumption of antibiotics and the use of broad-spectrum antibiotics for AOM in children aged 1-15 y at an emergency call service. Data on antibiotic use in AOM based only on prescribing overestimates the use of antibiotics.

Impact of improved treatment of sexually transmitted disease on HIV infection.

Grosskurth and colleagues report the outcomes of a randomized controlled trial to evaluate the impact of improved treatment of sexually transmitted diseases (STD) on HIV infection. The authors congratulate the research team on the high quality of the design and execution of their study. They are amazed by the reported 43% reduction in the incidence of HIV as a result of the medium-strength intervention. The effect upon other STDs is however less apparent. The researchers discussed possible effect modifications of different co-factors but concluded that bias is negligible or very limited. These authors do not however think that the researchers sufficiently consider the implications of the difference in baseline HIV prevalence between intervention and comparison communities. It is important to correct for the initial 14% difference in initial condition since the prevalent cases form the source of subsequent HIV infections. The authors therefore recalculated risk ratios using a correction factor for each of the six matched pair communities. In so doing the overall estimate of HIV reduction as a result of the intervention would be 33% probably a better estimate than the original 43%. The confidence interval for the effect was widened by the correction. A more sophisticated analysis should consider the possibility that frequencies changed during the research period since the HIV epidemic has most likely not yet reached its dynamic equilibrium. The authors stress in closing that a 33% reduction in the frequency of HIV is nonetheless remarkable for this type of intervention.

The antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL-producing Escherichia coli in Norway 2010-2011

Abstract Background: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10–15 years as part of a global pandemic. ESBL producers frequently express co-resistance to other important antimicrobial drug classes, limiting therapeutic options. This has led to regained interest in older antimicrobial agents. The aim of this study was to evaluate the antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin, as well as to perform a comparative analysis of resistance patterns in a nationwide collection of ESBL-producing E. coli. Methods: A nationwide collection of all 105 clinical isolates of ESBL-producing E. coli from the Norwegian Organisation for Surveillance of Antimicrobial Resistance (NORM) during 2010–2011 was analyzed. Detection and identification of ESBL-encoding genes were performed by PCR and sequencing for confirmation of ESBL variants of blaTEM and blaSHV (2010) or microarray (2011). Minimum inhibitory concentrations (MICs) or MIC correlates were determined using MIC gradient tests or VITEK 2, respectively. Comparative analysis of resistance patterns was performed. Results: All isolates were susceptible to fosfomycin, temocillin (urinary tract breakpoint) and meropenem. For mecillinam and nitrofurantoin, 6% and 9% of the isolates, respectively, were non-susceptible. A high level of susceptibility was also observed for amikacin (95%). In contrast, the non-susceptibility proportions to ampicillin (100%), cefotaxime (97%), ceftazidime (77%), aztreonam (87%), gentamicin (42%), tobramycin (52%), ciprofloxacin (76%) and trimethoprim-sulfamethoxazole (71%) were higher. Conclusions: Overall, the in vitro susceptibility to nitrofurantoin, fosfomycin, mecillinam and temocillin was high, indicating that these drugs are good options for treating uncomplicated urinary tract infections caused by ESBL-producing E. coli.

A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study

Following a TV documentary in 2013, there was a tremendous increase in low dose naltrexone (LDN) use in a wide range of unapproved indications in Norway. We aim to describe the extent of this sudden and unprecedented increase in LDN prescribing, to characterize patients and LDN prescribers, and to estimate LDN dose sizes.

Validation of a Simplified Netilmicin Dosage Regimen in Infants

The aim of this study was to validate a simplified high-dosage, extended-interval netilmicin dosage regimen for infants. A total of 129 infants receiving 163 treatment courses of netilmicin (6 mg/kg every 24 or 36 h depending on gestational age (GA), postnatal age and postmenstrual age) was analysed. Serum netilmicin concentrations were monitored before (Cmin), 30 min (C0.5h) after and 7.5 h (C7.5h) after the third dose. In 110 patients during first week of life mean C0.5h was 10.5 mg/l. Mean C0.5h was significantly lower (9.0 mg/l) in 38 infants older than 1 week of age. 14 of 15 patients with Cmin levels≥2 mg/l receiving netilmicin every 36 h were <28 weeks of gestation. In the first week of life significant correlations between GA and elimination half-life (p<0.001) and between plasma creatinine and elevated Cmin (p<0.002) were found, but no correlation between C0.5h and GA. In this high-dosage regimen a dosing interval of 48 h for GA<29 weeks, 36 h for GA 29–36 weeks and 24 h for full term babies seems appropriate, during first week of life, to avoid the majority of elevated trough levels and still obtain maximal therapeutic efficacy.

A pharmacist-led follow-up program for patients with coronary heart disease in North Norway–a qualitative study exploring patient experiences

BackgroundCoronary heart disease (CHD) is one of the leading causes of death worldwide. Scientific literature shows that prevention of CHD is inadequate. The clinical pharmacist’s role in patient-centred care has been shown favourable in a large amount of studies, also in relation to reduction of risk factors related to CHD. We developed and piloted a pharmacist-led follow-up program for patients with established CHD after hospital discharge from a hospital in North Norway. The aim of the present study was to explore how participants in the follow-up program experienced the program with regard to four main topics; medication knowledge, feeling of safety and comfort with medications, the functionality of the program and the clinical pharmacist’s role in the interdisciplinary team.MethodsWe performed semi-structured thematic interviews with four patients included in the program. After verbatim transcribing, we analysed the interviews using “qualitative content analyses” by Graneheim and Lundman. Trial registration http://www.clinicaltrials.gov: NCT01131715.ResultsAll participants appreciated the follow-up program because their medication knowledge had increased, participation had made them feel safe, they were reassured about the appropriateness of their medications, and they had become more involved in their own medication. The participants reported that the program was well structured and the clinical pharmacist was said to be an important caretaker in the health-care system. The importance of collaboration between pharmacists and physicians, both in hospital and primary care, was emphasized.ConclusionOur results indicate that the follow-up program was highly appreciated among the four participants included in this study. The results must be interpreted in the context of the health care system in Norway today. Here, few pharmacists are working in hospitals or in close relation to the general practitioners. In addition, physicians are short of time in order to supply appropriate medication information, both in hospital and primary care. Involving pharmacists in follow-up of patients with CHD seems to be highly appreciated among patients and may be a step towards improving patient care. The study is limited by the low number of participants.

Low-dose naltrexone and opioid consumption: a drug utilization cohort study based on data from the Norwegian prescription database

Low‐dose naltrexone (LDN) is used in a wide range of conditions, including chronic pain and fibromyalgia. Because of the opioid antagonism of naltrexone, LDN users are probably often warned against concomitant use with opioids. In this study, based on data from the Norwegian prescription database, we examine changes in opioid consumption after starting LDN therapy.

Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study

Low dose naltrexone (LDN) has become a popular off-label therapy for multiple sclerosis (MS). A few small, randomized studies indicate that LDN may have beneficial effects in MS and other autoimmune diseases. If proven efficacious, it would be a cheap and safe alternative to the expensive treatments currently recommended for MS. We investigated whether a sudden increase in LDN use in Norway in 2013 was followed by changes in dispensing of other medications used to treat MS. We performed a quasi-experimental before–and–after study based on population data from the Norwegian Prescription Database (NorPD). We included all patients that collected at least one LDN prescription in 2013, and had collected at least two medications with a reimbursement code for MS, or collected a medication with MS as the only indication in 2009 or 2010. Outcomes were differences in cumulative dispensed doses and incidence of users of disease modifying MS therapies, and medications used to treat MS symptoms two years before and two years after dispensing the initial LDN prescription. The eligible 341 patients collected 20 921 prescriptions in the observation period. Apart from changes in line with general trends in MS therapy in Norway, there was no difference in neither dispensed cumulative doses or number of prevalent users of MS specific medication. Initiation of LDN was not followed by reductions of other medications used to treat symptoms associated with MS.

MAT‐CAP: a novel medication assessment tool to explore adherence to clinical practice guidelines in community‐acquired pneumonia

Community‐acquired pneumonia (CAP) is a disease with high morbidity and mortality. Adherence to clinical practice guidelines (CPGs) in treatment of CAP is associated with favourable outcome. We aimed to develop and validate a medication assessment tool (MAT) to explore adherence to CPG recommendations in patients with CAP admitted to a Norwegian hospital. The tool is named MAT‐CAP.