Consensus recommendations on the use of daylight photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in Australia

Australia has the highest prevalence of actinic keratoses (AK) worldwide. Because of the risk of transformation of AK to invasive squamous cell carcinomas, consensus guidelines recommend that AK are removed using appropriate therapies to prevent progression to invasive disease. Daylight photodynamic therapy (PDT) is emerging as an efficacious treatment for AK, particularly for patients who require treatment of large areas of chronic actinic damage that can be exposed easily to daylight. Daylight PDT with methyl aminolevulinate (MAL) cream is a simple treatment for AK, almost painless, well tolerated and convenient, requiring minimal time in the clinic. Randomised controlled studies from northern Europe and Australia support the use of daylight PDT as an effective therapy for grade I and II AK on the face and scalp. There is sufficient daylight to conduct daylight PDT in Australia at any time of the year and during most weather conditions. Hence, daylight PDT with MAL can be included as an effective and well‐tolerated new treatment option for the treatment of AK in Australia. These consensus recommendations provide guidelines for Australian clinicians on the use of daylight PDT in the treatment of diagnosed AK.     

Insecticide-treated bednets for the prevention of Plasmodium falciparum malaria in Cambodia: a cluster-randomized trial

OBJECTIVES: To validate and quantify the impact of insecticide-treated bednets (ITN) on malaria morbidity and mortality in Cambodia. METHODS: A paired, cluster-randomized trial of ITN was conducted in Rattanakiri, North East Cambodia. Thirty-four villages with a total population of 10,726 were randomized to receive deltamethrin-impregnated bednets or to control (no net provision). Cross-sectional surveys measured Plasmodium falciparum prevalence at baseline and 10 months after ITN distribution. Village malaria volunteers in control and intervention villages treated dipstick-positive P. falciparum cases with artesunate and mefloquine. The resulting passive surveillance data were used as an estimate of the incidence of clinical P. falciparum infections. RESULTS: There was a protective efficacy of 28% in P. falciparum incidence (adjusted rate ratio 0.72, 95% CI 0.47-1.08) and 9% in P. falciparum prevalence (adjusted prevalence ratio 0.91, 95% CI 0.65-1.28) in ITN relative to control villages; however, neither of these estimates reached statistical significance. Individual-level analysis indicated a greater reduction in P. falciparum prevalence among under 5-year-olds (adjusted OR = 0.63, 95% CI 0.26-1.53) compared to older individuals (interaction P = 0.042). The protective efficacy of 35% (95% CI -28, 67%) with respect to clinical P. falciparum incidence in under 5-year-olds was more pronounced than the corresponding estimates for prevalence but was again not significant. CONCLUSIONS: Lack of statistical significance in the results is likely to be due to a lack of power. The analysis provides further evidence for ITN effectiveness in South East Asia, particularly among individuals under 5 years of age.     

Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study

BACKGROUND AND OBJECTIVES: This paper reports the results to 1 March 2006 of an ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that Creutzfeldt-Jakob disease (CJD), including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is transmissible via blood transfusion. MATERIALS AND METHODS: Sporadic CJD and fCJD cases with a history of blood donation or transfusion are notified to UKBS. All vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for donation records is instigated and the fate of all donations is identified by lookback. For cases with a history of blood transfusion, hospital and UKBS records are searched to identify blood donors. Details of identified recipients and donors are checked against the NCJDSU register to establish if there are any matches. RESULTS: CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5 fCJD cases reported as blood donors were confirmed to have donated labile components transfused to 66, 20, and 11 recipients respectively. Two vCJD recipients have appeared on the NCJDSU register as confirmed and probable vCJD cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively after receiving non-leucodepleted red blood cells (RBCs) from two different donors who developed clinical symptoms approximately 40 and 21 months after donating. A third recipient, given RBC donated by a further vCJD case approximately 18 months before onset of clinical symptoms, had abnormal prion protein in lymphoid tissue at post-mortem (5-years post-transfusion) but had no clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of labile blood components donated by 125 and 24 donors respectively. Two recipients who developed vCJD were linked to donors who had already appeared on the NCJDSU register as vCJD cases (see above). No further links were established. CONCLUSION: This study has identified three instances of probable transfusion transmission of vCJD infection, including two confirmed clinical cases and one pre- or sub-clinical infection. This study has not provided evidence, to date, of transmission of sCJD or fCJD by blood transfusion, but data on these forms of diseases are limited.     

Brain-derived neurotrophic factor silences GABA synapses onto hypothalamic neuroendocrine cells through a postsynaptic dynamin-mediated mechanism

In the paraventricular nucleus of the hypothalamus (PVN), experimental stress paradigms that suppress gamma-aminobutyric acid (GABA) inputs to parvocellular neuroendocrine cells (PNCs) also increase the expression of brain-derived neurotrophic factor (BDNF). In the adult CNS, BDNF regulates the efficacy of GABAergic transmission, but its contributions to functional changes at inhibitory synapses in the PVN have not been investigated. Analysis of quantal transmission revealed a decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in response to BDNF with no accompanying changes in their amplitude. These effects were completely blocked by prior inclusion of the TrKB receptor antagonist K252a in the patch pipette. Inclusion of a dynamin inhibitory peptide in the patch pipette also blocked the effects of BDNF, consistent with an all-or-none removal of clusters of postsynaptic GABAA receptors. Finally, to confirm a decrease in the availability of postsynaptic GABAA receptors, we tested the effects of BDNF on focal application of the GABAA agonist muscimol. Postsynaptic responses to muscimol were reduced after BDNF. Collectively, these data indicate that BDNF remodels functional synaptic contacts putatively by reducing the surface expression of postsynaptic GABAA receptors.     

Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines

Infantile haemangiomas (IH) are common birthmarks in babies consisting of dilated blood vessels. They are also known as strawberry naevi. Most of them grow for a few months, then gradually shrink spontaneously over a period of months or years. However, in about 15% of cases they can cause serious functional problems when they involve important structures such as the eye, ear, mouth, nose and the peri‐anal area. In addition they can sometimes resolve, but leaving significant disfigurement. In 2008 it was reported that the beta‐blocker drug propranolol, given orally (by mouth), was very effective in causing these birthmarks to shrink rapidly. This paper is designed to provide guidance to doctors on how best to administer propranolol to children with IH. Developing the guidelines involved several stages: an international survey of current practice in eight European countries; a systematic review of the literature; collecting current local guidelines from 19 centres leading to the generation of 70 statements. These 70 statements were then scrutinised by 19 experts from relevant specialities (Dermatology, Paediatrics, Paediatric Cardiology and Paediatric ENT surgery). Using an established research protocol, agreement was reached by these experts on 47 statements covering eight categories. These categories include: indications for starting propranolol (i.e. it which situations it should be used); contraindications (i.e. in which situations it should not be used); pre‐treatment tests needed; initiation of treatment; monitoring during treatment and when to stop treatment. They also cover treatment of children with additional medical complications.Although these guidelines are UK‐based, the authors hope that they will be useful in other European countries also.     

Prolonged Vaginal Bleeding in an Adolescent Secondary to a Foreign Body: Need for a Comprehensive Assessment and Complex Surgery

Background

Heavy, prolonged menstrual bleeding is common in adolescents and results from a variety of etiologies.

Prevalence and predictors of refractive error in a genetically isolated population: the Norfolk Island Eye Study

Background: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. Design: Population‐based study on Norfolk Island, South Pacific. Participants: All permanent residents on Norfolk Island aged ≥15 years were invited to participate. Methods: Patients underwent non‐cycloplegic autorefraction, slit‐lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. Main Outcome Measures: Prevalence and multivariate associations of refractive error and myopia. Results: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15–81). Three hundred and seventy‐six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥?1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). Conclusions: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.