Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

BACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.

Evolving Project ECHO: delivery of pediatric pain core competency learning for interprofessional healthcare providers.

Introduction: Healthcare providers (HCPs) practicing in community settings are critical to improving access to pain care, yet there are significant gaps in training opportunities designed for interprofessional learners. Project Extension for Community Healthcare Outcomes (Project ECHO®) is an established model for delivering online HCP education through virtual clinics and cultivating a community of practice. However, to our knowledge, the integration of pain core competency education into the ECHO® model has not been previously attempted. This innovation could enhance the ECHO® model while also addressing the growing calls for more accessible interprofessional pain curricula. This paper describes efforts to implement and evaluate core competency curricula within the context of Pediatric Project ECHO for Pain, one of the first pediatric-pain focused ECHO programs in the world. Methods: Needs assessments informed curricula development. The first delivered core competency model consisted of synchronous webinar-style sessions while the second model included a mixture of asynchronous (eLearning course) and synchronous (virtual clinical debrief) elements. A convenience sample of HCPs was recruited from ECHO program registrants. Participants completed baseline and follow-up surveys to assess core competency acceptability as well as impact on knowledge and self-efficacy related to managing pediatric pain. Usability of the eLearning platform (model 2 only) was also evaluated. Surveys used 5-point Likert scales to capture outcomes. A priori targets included mean scores ≥4/5 for acceptability and ≥80% of learners reporting knowledge and self-efficacy improvements. The study received local research ethics approval. Results: The core competency was found to be highly acceptable to interprofessional learners (n = 31) across delivery models, surpassing a priori targets. Specifically, it was characterized as a worthwhile and satisfactory experience that was helpful in supporting learning. The core competency was also associated with improvements in knowledge and self-efficacy by 97% and 90% of learners, respectively. The eLearning platform was reported to have high usability with clinically realistic cases (100% of respondents) that were helpful to inform care delivery (94% of respondents). Conclusion: The integration of core competency learning within the Project ECHO® model was a successful approach to deliver pediatric pain education to interprofessional HCPs.

Spectrum of Clinical Presentations, Imaging Findings, and HLA Types in Immune Checkpoint Inhibitor-Induced Hypophysitis.

Context: Hypophysitis is a known immune-related adverse event (irAE) of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and less often with PD-1/PD-L1 inhibitors. Objective: We aimed to determine clinical, imaging, and HLA characteristics of CPI-induced hypophysitis (CPI-hypophysitis). Methods: We examined the clinical and biochemical characteristics, magnetic resonance imaging (MRI) of the pituitary, and association with HLA type in patients with CPI-hypophysitis. Results: Forty-nine patients were identified. Mean age was 61.3 years, 61.2% were men, 81.6% were Caucasian, 38.8% had melanoma, and 44.5% received PD-1/PD-L1 inhibitor monotherapy while the remainder received CTLA-4 inhibitor monotherapy or CTLA-4/PD-1 inhibitor combination therapy. A comparison of CTLA-4 inhibitor exposure vs PD-1/PD-L1 inhibitor monotherapy revealed faster time to CPI-hypophysitis (median 84 vs 185 days, P < .01) and abnormal pituitary appearance on MRI (odds ratio 7.00, P = .03). We observed effect modification by sex in the association between CPI type and time to CPI-hypophysitis. In particular, anti-CTLA-4 exposed men had a shorter time to onset than women. MRI changes of the pituitary were most common at the time of hypophysitis diagnosis (55.6% enlarged, 37.0% normal, 7.4% empty or partially empty) but persisted in follow-up (23.8% enlarged, 57.1% normal, 19.1% empty or partially empty). HLA typing was done on 55 subjects; HLA type DQ0602 was over-represented in CPI-hypophysitis relative to the Caucasian American population (39.4% vs 21.5%, P = 0.01) and CPI population. Conclusion: The association of CPI-hypophysitis with HLA DQ0602 suggests a genetic risk for its development. The clinical phenotype of hypophysitis appears heterogenous, with differences in timing of onset, changes in thyroid function tests, MRI changes, and possibly sex related to CPI type. These factors may play an important role in our mechanistic understanding of CPI-hypophysitis.

Pediatric Project ECHO® for Pain: implementation and mixed methods evaluation of a virtual medical education program to support interprofessional pain management in children and youth.

BACKGROUND: Pediatric pain is a complex health challenge requiring a multi-modal management approach. It is critical that healthcare providers (HCPs) have access to ongoing, flexible education and mentorship specific to pediatric pain. However, there are significant gaps in available pain education and a need for more opportunities to support interprofessional training. Project Extension for Community Healthcare Outcomes (Project ECHO®) is a model for delivering online HCP education and cultivating a virtual community of practice. Within the pediatric pain setting, ECHO® has potential to improve local access to specialized pain knowledge, particularly among the physicians, nurses, and allied health providers who primarily manage these cases in community and hospital settings across rural and urban environments. The purpose of this study was three-fold. First, to evaluate the feasibility (participation levels, acceptability) of implementing Project ECHO® in the context of pediatric pain. Second, to measure preliminary program impacts on HCP knowledge, self-efficacy, and clinical practice. Third, to characterize HCP program engagement levels before and after onset of the COVID-19 pandemic. METHODS: A needs assessment was conducted to identify interprofessional education gaps and inform the program curriculum. The no-cost Pediatric ECHO® for Pain program offered TeleECHO sessions (didactic and case-based learning) as well as foundational education. Surveys were distributed at baseline and 6 months to assess outcomes using 7-point Likert scales. Participant engagement was assessed for periods prior to and during the COVID-19 pandemic. Descriptive and inferential statistical analyses were conducted. RESULTS: Eighty-five TeleECHO sessions were hosted, with a mean attendance of 34.1 ± 23.4 HCPs. Acceptability scores at 6 months (n = 33) ranged from 5.0 ± 1.4 to 6.5 ± 0.5. Participants reported statistically significant (p < 0.05) improvements in knowledge (7 out of 7 topics) and self-efficacy (8 out of 9 skills). Most participants reported positive practice impacts, including improved satisfaction with managing children with pain. Exploratory analyses showed a trend of greater engagement from ECHO® learners after onset of the COVID-19 pandemic. CONCLUSIONS: Project ECHO® is a feasible and impactful model for virtual education of interprofessional HCPs in managing pediatric pain.

Carbon dioxide levels in neonates: what are safe parameters?

There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5-64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0-7.3 kPa: 45.0-54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. IMPACT: There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5-7 kPa was inferred following systematic review.

Genetic & virulence profiling of ESBL-positive E. coli from nosocomial & veterinary sources.

CTX-M genes are the most prevalent ESBL globally, infiltrating nosocomial, community and environmental settings. Wild and domesticated animals may act as effective vectors for the dissemination of CTX-producing Enterobacteriaceae. This study aimed to contextualise blaCTX-M-14-positive, cephalosporin-resistant Enterobacteriaceae human infections and compared resistance and pathogenicity markers with veterinary isolates. Epidemiologically related human (n=18) and veterinary (n=4) blaCTX-M-14-positive E. coli were fully characterised. All were typed by XbaI pulsed field gel electrophoresis and ST. Chromosomal/plasmidic locations of blaCTX-M-14 were deduced by S1-nuclease digestion, and association with ISEcp1 was investigated by sequencing. Conjugation experiments assessed transmissibility of plasmids carrying blaCTX-M-14. Presence of virulence determinants was screened by PCR assay and pathogenicity potential was determined by in vitro Galleria mellonella infection models. 84% of clinical E. coli originated from community patients. blaCTX-M-14 was found ubiquitously downstream of ISEcp1 upon conjugative plasmids (25-150 kb). blaCTX-M-14 was also found upon the chromosome of eight E. coli isolates. CTX-M-14-producing E. coli were found at multiple hospital sites. Clonal commonality between patient, hospitals and livestock microbial populations was found. In vivo model survival rates from clinical isolates (30%) and veterinary isolates (0%) were significantly different (p<0.05). Co-transfer of blaCTX-M-14 and virulence determinants was demonstrated. There is evidence of clonal spread of blaCTX-M-14-positive E. coli involving community patients and farm livestock. blaCTX-M-14 positive human clinical isolates carry a lower intrinsic pathogenic potential than veterinary E. coli highlighting the need for greater veterinary practices in preventing dissemination of MDR E. coli among livestock.

The challenges of diagnosis and treatment of dementia in Down's syndrome.

OBJECTIVES: People with Down syndrome (DS) are at high risk for developing dementia and early diagnosis is vital in enhancing quality of life. Our aim was to compare our practice to consensus recommendations on evaluation, diagnosis and pharmacological treatment of individuals with DS who develop dementia. We also aimed to establish the average time taken to make a diagnosis of dementia and to commence pharmacotherapy, and to assess tolerability to acetylcholinesterase inhibitors. METHODS: Retrospective chart review in an exhaustive sample containing all current service users attending our service with DS and a diagnosis of dementia (n=20). RESULTS: The sample was 75% female and 70% had a moderate intellectual disability. The average age at diagnosis of dementia was 52.42 years old. The average time to diagnosis from first symptom was 1.13 years and the average time to commence pharmacotherapy was 0.23 years. A total of 17 patients commenced on acetylcholinesterase inhibitors, and of these seven discontinued medication due to side-effects or lack of efficacy. CONCLUSIONS: The results on anticholinesterases add to the limited pool of data on treatment of dementia in DS. There was an identified need to improve the rates of medical, vision and hearing assessments, and prospective screening. Deficiencies in screening and diagnosis may be addressed by implementing a standardised dementia assessment pathway to include prospective screening and longitudinal assessment using easily administered scales. We highlight the importance of improving the diagnostic process, as a vital window of opportunity to commence a comprehensive care plan may be lost.

Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005-2006.

BACKGROUND: Exposure to damp indoor environments is associated with increased risk of eczema, allergy and asthma. The role of dampness-related exposures and risk of allergic diseases are yet to be fully explored in the US population. OBJECTIVE: We assess whether exposure to fungi, house dust mites and endotoxin increases the risk of eczema, allergy and asthma in children and adults participating in NHANES 2005-2006. METHODS: A total of 8412 participants (2849 were children aged between 6 and 17 years) were recruited in the 2005-2006 survey. We used multiple logistic regression to investigate whether mildew/musty odour and increased concentrations of Alternaria alternata allergen, Aspergillus fumigatus antigens, house dust mite and endotoxin antigens increase the risk of eczema, allergy and asthma. We stratified models by total IgE < 170 and ≥ 170 KU/L to assess allergic and non-allergic asthma outcomes. Exposure to multiple biological agents and risk of reporting eczema, allergy and asthma were also investigated. RESULTS: Reporting of a mildew/musty odour was associated with increased risk of childhood asthma (OR 1.60; 95% CI 1.17-2.19), and adult eczema, allergy and asthma (OR 1.92; 95% CI 1.39-2.63, OR 1.59 95% CI 1.26-2.02 and OR 1.61 95% CI 1.00-2.57, respectively). Risk of asthma was associated with total IgE ≥ 170 KU/L in children (OR 1.81; 95% CI 1.01-3.25) and total IgE < 170 KU/L in adults (OR 1.91; 95% CI 1.07-3.42). Children and adults exposed to more than eight biological agents present in the home were at reduced risk of eczema (OR 0.17; 95% CI 0.04-0.77) and asthma (OR 0.49; 95% CI 0.25-0.97), respectively. CONCLUSION: Exposure to a mildew/musty odour, as a proxy for exposure to fungus, was implicated in an increased risk of atopic diseases. Sensitisation may play a different role in children and adults, and exposure to multiple allergens may reduce the risk of atopic disease.

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia.

Burkholderia cenocepacia is a bacterial pathogen which causes severe respiratory infections in cystic fibrosis (CF). These studies were aimed at gaining an insight into the iron acquisition strategies of B. cenocepacia. In iron restricted conditions, genes associated with the synthesis and utilisation of ornibactin (pvdA, orbA, orb F) were significantly upregulated compared to the expression of pyochelin associated genes (pchD, fptA). In the absence of alternative iron sources, B. cenocepacia J2315 and 715j utilised ferritin and haemin, but not transferrin or lactoferrin for growth. Significantly, mutants unable to produce ornibactin, (715j-orbI) or ornibactin and pyochelin, (715j-pobA), utilised haemin and ferritin more efficiently than the wild-type. Moreover, both mutants were also able to utilise lactoferrin for growth (P ≤ 0.01) and additionally 715j-pobA utilised transferrin (P ≤ 0.01), potentially facilitating adaptation to the host environment. Furthermore, B. cenocepacia increased ornibactin gene expression in response to pyoverdine from Pseudomonas aeruginosa (P ≤ 0.01), demonstrating the capacity to compete for iron in co-colonised niches. Pyoverdine also significantly diminished the growth of B. cenocepacia (P < 0.001) which was related to its iron chelating activity. In a study of three B. cenocepacia sequential clonal isolates obtained from a CF patient over a 3.5 year period, ornibactin upregulation in response to pyoverdine was less pronounced in the last isolate compared to the earlier isolates, as was growth in the presence of haemin and ferritin, indicating alternative iron acquisition mechanism(s) may dominate as chronic infection progresses. These data demonstrate the multifaceted iron acquisition strategies of B. cenocepacia and their capacity to be differentially activated in the presence of P. aeruginosa and during chronic infection.

Volatile anaesthesia during cardiopulmonary bypass.

Since its inception, administering and ensuring anaesthesia during cardiopulmonary bypass has been challenging. Partly because of the difficulty of administering volatile agents during cardiopulmonary bypass, total intravenous anaesthesia has been a popular technique used by cardiac anaesthetists in the last two decades. However, the possibility that volatile agents reduce mortality and the incidence of myocardial infarction by preconditioning the myocardium has stimulated a resurgence of interest in their use for cardiac anaesthesia. The aim of this review is to provide an overview of the administration of volatile anaesthetic agents during cardiopulmonary bypass for the maintenance of anaesthesia and to address some of the practical issues that are involved in doing so.

Cavernous and inferior petrosal sinus sampling and dynamic magnetic resonance imaging in the preoperative evaluation of Cushing's disease.

The surgical management of Cushing's disease is often complicated by difficulties detecting corticotropic adenomas. Various diagnostic modalities are used when conventional magnetic resonance imaging (MRI) is negative or inconclusive. We sought to analyze our use of two such modalities in the surgical management of Cushing's disease: (1) cavernous/inferior petrosal sinus sampling (central venous sampling, CVS) for adrenocorticotropic hormone and (2) dynamic MRI (dMRI). We conducted a single-center, retrospective review of all patients with Cushing's disease treated by a single neurosurgeon with endonasal transsphenoidal surgery. Accuracy of adenoma localization with CVS and dMRI was analyzed. Ninety-one consecutive patients were included. Pathology confirmed an adenoma in 66. Preoperative dMRI and CVS were performed in 40 and 37 patients, respectively, with 20 undergoing both studies. Surgical pathology was positive for adenoma in 31 dMRI patients, 25 CVS patients, and 13 who underwent both. Among patients with pathology confirming an adenoma, dMRI identified a lesion in 96.8% and correctly lateralized the lesion in 89.7%, while CVS correctly lateralized in 52.2-65.2% (depending on location of sampling). Among patients with both studies, dMRI and CVS correctly lateralized in 76.9 and 61.5-69.2%, respectively. Accuracy of CVS improved if only patients with symmetric venous drainage were considered. In this mixed population of Cushing's disease patients, dMRI was more accurate than CVS at localizing adenomas, supporting the use of advance MRI techniques in the work-up of Cushing's disease. CVS, however, remains an important tool in the workup of Cushing's syndrome.

Pheochromocytoma crisis is not a surgical emergency.

CONTEXT: Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma. OBJECTIVE: We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated. DESIGN: Retrospective cohort study (1993-2011); literature review (1944-2011). SETTING: Tertiary referral center. PATIENTS: There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature. INTERVENTION: Medical management of pheochromocytoma crisis; adrenalectomy. MAIN OUTCOME MEASURE(S): Perioperative complications, conversion, and mortality. RESULTS: In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002). CONCLUSIONS: Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.

Are marine environmental pollutants influencing global patterns of human disease?

Thousands of toxic chemicals, many of which pollute marine ecosystems, potentially cause diseases, but building a consensus view of the significance of human body burdens of environmental chemicals is proving difficult. Causative mechanisms are often lacking. Older members of the population, of which there are increasing numbers worldwide, accumulate higher body burdens than the young, and may be especially at risk. It also remains unclear when crucially sensitive periods for chemical exposures occur across the life course. Very early exposures may lead to diseases much later on. The current lack of robust science upon which to base high quality expert advice is hampering effective policymaking that leads to further reductions in marine pollution, greater protection of marine life and lowering of risks to human health.

Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy.

BACKGROUND: Methylaminolaevulinate (MAL)-photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death. OBJECTIVES: This study investigates real-time changes in localized tissue blood oxygen saturation and perfusion in conjunction with PpIX fluorescence monitoring for the first time during dermatological MAL-PDT. METHODS: Oxygen saturation, perfusion and PpIX fluorescence were monitored noninvasively utilizing optical reflectance spectroscopy, laser Doppler perfusion imaging and a fluorescence imaging system, respectively. Patients attending for standard dermatological MAL-PDT were recruited to this ethically approved study and monitored prior to, during and after light irradiation. RESULTS: Significant reductions in mean blood oxygen saturation (P < 0·005) and PpIX fluorescence (P < 0·001) were observed within the first minute of irradiation (4·75 J cm(-2) ) while, in contrast, perfusion was observed to increase significantly (P < 0·01) during treatment. The changes in oxygen saturation and PpIX fluorescence were positively correlated during the initial phase of treatment (r(2) = 0·766). CONCLUSIONS: Rapid reductions in the localized blood oxygen saturation have been observed for the first time to occur clinically within the initial minutes of light irradiation and positively correlate with the concurrent PpIX photobleaching. Furthermore, perfusion increases, suggesting that the microvasculature compensates for the PDT-induced oxygen depletion.

Comparison of protoporphyrin IX accumulation and destruction during methylaminolevulinate photodynamic therapy of skin tumours located at acral and nonacral sites.

BACKGROUND: Topical photodynamic therapy (PDT) is successful in the treatment of nonmelanoma skin cancers and associated precancers, but efficacy is significantly reduced in actinic keratosis lesions not located on the face or scalp. OBJECTIVES: To compare the changes in protoporphyrin IX (PpIX) fluorescence in lesions undergoing routine methylaminolevulinate (MAL) PDT and the clinical outcome observed 3 months after treatment in lesions located at acral and nonacral sites. METHODS: This study was a noninterventional, nonrandomized, observational study, which monitored changes in PpIX fluorescence in 200 lesions during standard dermatological MAL-PDT. These data were subsequently analysed in terms of lesions located at acral and nonacral sites. RESULTS: Clinical clearance was significantly reduced (P < 0·01) in acral skin lesions when compared with lesions located at nonacral sites. The accumulation and destruction of PpIX fluorescence was significantly reduced in these acral lesions (P < 0·05 and P < 0·001, respectively). Specifically, lesion location at acral sites significantly reduced changes in PpIX fluorescence in actinic keratosis lesions during MAL-PDT (P < 0·01 and P < 0·05). CONCLUSIONS: These data suggest that reduced PpIX accumulation and the subsequent reduction in PpIX photobleaching within acral lesions result in the reduced responsiveness of these lesions to MAL-PDT. Future work should therefore aim to improve photosensitizer accumulation/photobleaching within lesions located at acral sites.

The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy.

Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized to successfully treat licensed indications (e.g. actinic keratosis (AK), superficial basal cell carcinoma (sBCC) and Bowen's disease (BD)) in the UK. Air cooling devices (ACD) are commonly utilized as a method of pain relief, however the effect of this on treatment outcome has never been extensively investigated. This non-randomized, retrospective observational controlled study investigated whether the application of the ACD limited photosensitiser (protoporphyrin IX - PpIX) photobleaching during irradiation and/or subsequent clinical outcome. Patients utilizing the ACD throughout treatment were observed to undergo significantly less PpIX photobleaching than the control group (P<0.001) and complete clinical clearances observed at 3 months were also reduced within the ACD group. Separate analysis of the different lesion types indicated that significantly less photobleaching occurred in AK lesions with ACD and all lesion types failed to fully utilize the accumulated PpIX when ACD was employed. The application of the ACD as pain relief during light irradiation therefore resulted in lower PpIX photobleaching which corresponded to a reduction in the efficacy of PDT treatment. Whilst the ACD is an effective method of dermatological PDT analgesia it should be utilized as sparingly as possible to minimize any deleterious effects on treatment outcome.

Effect of MAL-photodynamic therapy on hypertrophic scarring.

BACKGROUND: Patients with localised scleroderma receiving aminolevulinic acid (ALA)/methyl aminolevulinic acid (MAL)-photodynamic therapy (PDT) were noted to show a reduction in skin tightness, suggesting that this therapy reduces skin sclerosis. Karrer and colleagues treated patients with 5-ALA-PDT once or twice weekly for 3-6 months and in all patients the therapy was reported to be highly effective for sclerotic plaques. In view of the potential benefit of PDT in reducing skin sclerosis, the following study looks at the possible clinical and histological effects of topical PDT on the mechanism of scarring, looking particularly at hypertrophic scars. METHODS: Patients with long standing hypertrophic scars were treated with MAL-PDT on two occasions at week apart, and repeated for 3 sessions at 6-weekly intervals. PDT effect was studied by means of fluorescence imaging throughout the treatment and biopsies were taken prior to and 6 weeks post-treatment to observe histological changes. RESULTS AND CONCLUSIONS: Six weeks following the treatment the scarred areas had significantly softened and become more flexible clinically and histologically there had been a significant increase in elastin fibres. This suggests that ALA/MAL-PDT may be a useful treatment or adjuvant therapy in the treatment of scarring.

Psychological variables as predictors of adherence to treatment by continuous positive airway pressure.

STUDY OBJECTIVES: We examined whether psychological variables enable us to predict adherence to CPAP in order to construct a predictive model to identify patients at risk of abandoning treatment. METHOD: One hundred and twenty-two Obstructive Sleep Apnoea (OSA) patients were studied before and one month after beginning CPAP treatment. All patients completed four psychological evaluation instruments before CPAP treatment: a health perception questionnaire (Nottingham Health Profile: NHP), a mental health rating scale (Hospital Anxiety and Depression Scale: HADS) and two disease-specific questionnaires that measure the patient's understanding of OSA and its treatment (Apnea Knowledge Test: AKT) and his attitudes to OSA and CPAP (Apnea Beliefs Scale: ABS). RESULTS: Thirty percent of the participants were non-adherent at one month. Decision-tree analysis indicated that it was possible to correctly classify 85.7% of non-adherent patients using three baseline factors (Emotional reactions score [NHP], age, and total score on ABS). Logistic regression analyses confirmed these two psychological variables as independent predictors of adherence. CONCLUSION: Assessing psychological well-being and subjective health status at onset of CPAP enables the identification of patients at risk of abandoning CPAP treatment. This subgroup could then be targeted early to receive supportive and educational measures to improve adherence rates.

Waiting for change: symptom resolution after adrenalectomy for Cushing's syndrome.

BACKGROUND: The debilitating symptoms and physical changes from Cushing's syndrome may resolve after treatment, but the time course to resolution is not well established. METHODS: Between February 1995 and May 2007, 60 patients underwent adrenalectomy for Cushing's syndrome. Pre-operative and operative variables were collected from a prospective database. Long-term follow-up was obtained via patient survey. RESULTS: Unilateral adrenalectomy was performed in 53% and a bilateral adrenalectomy in 47% of patients. Median time to diagnosis was 24 months (range, 1-384). Three percent had intra-operative complications, and 28% developed post-operative complications. Steroids were required post-operatively for a median of 30 months after unilateral adrenalectomy (range, 0-96). At a median follow-up of 3.7 years (range, 0-13.3), 85% of patients are still alive. The majority of the physical changes resolved after adrenalectomy. The time to symptom resolution varied from a few weeks to up to 4 years. Most of the physical changes resolved by a mean of 7-9 months after surgery. Quality of life improved in 78% of patients, with 68% improving dramatically (P < .001). CONCLUSION: Adrenalectomy can provide excellent palliation of the symptoms of cortisol excess and can dramatically improve patient quality of life, but both patients and physicians must know that these changes may take years.