Intramuscular injections of botulinum toxin for the treatment of upper back myofascial pain syndrome: A systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a synthesis of the evidence on intramuscular botulinum toxin injections for upper back MPS. DATABASES AND DATA TREATMENT: A systematic review of the literature was performed on the PubMed, Scopus and Cochrane Library, using the following formula: ("botulinum") AND ("musculoskeletal") AND ("upper back pain") OR ("myofascial pain"). RESULTS: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anaesthetic injections + dry needling or anaesthetic injections. The analysis of the trials revealed modest methodological quality: one "Good quality" study, one "Fair" and the other "Poor". No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, weak power analysis, different clinical scores used and non-comparable follow-up periods. Even if there is no conclusive evidence, the favourable safety profile and the positive results of some secondary endpoints suggest a potentially beneficial action in pain control and quality of life. CONCLUSION: The currently available studies show conflicting results. Their overall low methodological quality does not allow for solid evidence of superiority over other comparison treatments. Further insights are needed to properly profile patients who could benefit more from this peculiar injective approach. SIGNIFICANCE: The randomized controlled trials included in this review compared using botulinum toxin to treat upper back MPS with placebo or active treatments (e.g., dry needling or anaesthetics) showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery and disability reduction make it an interesting treatment, particularly in the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed.

Comparative FE biomechanical and microbial adhesion analyses on an implanted humerus.

Objective: In this study a multi fragment humeral fracture, treated with locking plate system implant, was investigate and compared with a healthy humerus by the mining of a Finite Element (FE) analysis. Locking plate implant, in this case AxSOS 3® Titanium produced by Stryker is the preferred solution in presence of multiple fracture or osteoporosis. Methods: Loading conditions were imposed by rotating of 52,5° respect the vertical axe, both the humeri (healthy and fractured), fixing distal end, and loading the top of bones with a vertical force of 543 N (Newton). This finite element analysis aimed to compare stability of implanted humerus, implant-bone interface, stress shielding, with those related to a healthy one. A microbial adhesion analysis was also performed on the implant's material. Results: Results obtained by FE analysis confirm a good agreement of the mechanical behavior of the models tested. The maximum values of the registered stressed, are of about 45 MPa (Mega Pascal) for the intact humerus and 113 MPa for the fractured one. Displacements, confirm higher values on the fractured humerus and no viable bacteria were found after microbial adhesion analyses.Conclusion: comparison between healthy and fractured humerus showed an optimal stability of the implant, when contact surfaces optimization and screws insertion are correctly performed.

Oxygen-ozone therapy for the treatment of low back pain: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of the study was to review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of low back pain (LBP), to understand its therapeutic potential and compare it with other available treatment options. MATERIALS AND METHODS: A systematic review was performed on the PubMed and Scopus databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) published in the last 20 years, (3) dealing with OOT in patients with LBP and herniated disc, (4) comparing the results of OOT with those of other treatments. The risk of bias was assessed by the Cochrane Risk of Bias tool. RESULTS: Fifteen studies involving 2597 patients in total were included. Patients in the control groups received different treatments, from oral drugs to other injections, instrumental therapy and even surgery: corticosteroids were used in 5 studies, analgesic therapy in 2 studies; placebo, microdiscectomy, laser-therapy, TENS and postural rehabilitation, percutaneous radiofrequency intradiscal thermocoagulation and psoas compartmental block were tested in the other trials. Looking at the quality of the literature, none of the studies included reached "good quality" standard, 3 were ranked as "fair" and the rest were considered "poor". Comparison of OOT results with other approaches showed that, in the majority of studies, OOT was superior to the control treatment, and also when compared to microdiscectomy, ozone showed non inferiority in terms of clinical outcomes. CONCLUSIONS: The analysis of literature revealed overall poor methodologic quality, with most studies flawed by relevant bias. However, OOT has proven to be a safe treatment with beneficial effects in pain control and functional recovery at short to medium term follow-up.

Use of public water supply fluoride concentration as an indicator of population exposure to fluoride in England 1995-2015.

Public health monitoring of Community Water Fluoridation (CWF) schemes requires estimates of exposure to fluoride in public water supplies (PWS). We aimed to use routine data to estimate population exposure to PWS-fluoride in England and to determine whether PWS-fluoride exposure from 2005 to 2015 could be used as a proxy for exposure for 1995-2004, when fluoride concentration data that could be linked to population health data were unavailable. We calculated annual mean water supply zone PWS-fluoride concentrations from monitoring data for 1995-2015, stratified by fluoridation scheme-flagging. We allocated annual 2005-2015 mean PWS-fluoride concentrations to small area boundaries to describe population exposure within five concentration categories (< 0.1 to ≥ 0.7 mg/L). We compared zone-level 1995-2004 and 2005-2015 mean PWS-fluoride concentrations using Spearman correlation. Most (72%) of the population received PWS with < 0.2 mg/L fluoride and 10% with ≥ 0.7 mg/L. Fluoride concentrations in 1995-2004 and 2005-2015 were similar (median 0.11 mg/L (lower quartile-upper quartile (LQ-UQ) 0.06-0.17) and 0.11 mg/L (LQ-UQ 0.07-0.17), respectively) and highly correlated (coefficient 0.93) if un-fluoridated but differed (1995-2004 median 0.78 mg/L (LQ-UQ 0.59-0.92); 2005-2015 0.84 mg/L (LQ-UQ 0.72-0.95)) and correlated weakly (coefficient 0.31) if fluoridated. Fluoride concentrations in 2005-2015 approximate those in 1995-2004 but with a greater risk of misclassification in fluoridation schemes.

Assessment of pharmacogenomic SLCO1B1 assay for prediction of neuromuscular pain in type 2 diabetes mellitus and cardiovascular patients: preliminary results.

OBJECTIVE: At present, several strategies for preventing neuromuscular pain in Type 2 Diabetes Mellitus (T2DM) have been investigated. Recently, findings on genetic variants associated with adverse events to statin-based therapy have been reported. The study aimed at measuring whether Pharmacogenomics (PGx) profile can affect neuromuscular pain in patients carrying T2DM and cardiovascular diseases. An extensive panel of 5 polymorphisms on 4 candidate genes, previously validated as significant markers related to Sulphonylureas and Glitinides (SU-G) plus Simvastatin neuromuscular toxicity, is herein analyzed and discussed. PATIENTS AND METHODS: We genotyped 76 T2DM patients carrying cardiovascular dyscrasia undergone anti-diabetic and anti-cholesterolemic polypharmacy. 35 subjects out of the total received concurrent SU-G and Statin-based therapy. Candidate variants consisted of drug transporters, such as Solute Carrier Organic 1B1 (SLCO1B1) Val174Ala ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug biotransformers of Cytochrome P450 Family (CYP) including CYP2C9*2 CYP2C9*3 CYP2C8*3, and CYP3A4*22. Moreover, we also focused on an early outline evaluation of the genotyping costs and benefits. RESULTS: 6 out of 35 patients treated with SU-G plus statins (17.1% experienced adverse neuropathy events). Pharmacogenomics analysis showed a lack of any correlation between candidate gene polymorphisms and toxicity, except for the SLCO1B1 T521C allele; 14.3% of patients had a high risk for grade >2 neuromuscular pain (Odds Ratio [OR] 2.61.95% CI 0.90-7.61, p=0.03). CONCLUSIONS: The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits.

Biodegradable antioxidant chitosan films useful as an anti-aging skin mask.

Cosmetics, personal care and biomedical products obtained by bio-based polymers and natural bioactive compounds are a new growing market. The ecological awareness is changing consumers' demands, causing consumers to look for more sustainable options, with a reduced environmental impact. The innovation of this work was to develop a natural polymer matrix (chitosan) entrapping antioxidant actives compounds such as annatto (Bixa Orellana L.) and vitamin C with potential application as sustainable anti-aging skin mask treatment. Films of chitosan (Ch) and reacetylated chitosan (RCh), exhibiting different degrees of acetylation (DA = 13.3 and 33.9%, respectively), were produced. The formulations of active films of chitosan (BCh) and reacetylated chitosan (BRCh) were 1% (w/w) of chitosan, 1% (w/w) of annatto powder, 5% (w/w) of vitamin C and 1% (w/w) of glycerol (as plasticizer). Reacetylated chitosan films (DA = 33.9%) presented higher water affinity than chitosan films (DA = 13.3%). The elongation of RCh and BRCh increased and the resistance decreased, as compared to Ch and BCh. The antioxidants compounds (annatto and vitamin C) of BRCh films released faster than BCh films. Thus, the BRCh films showed potential application as an anti-aging skin mask.

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers.

Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

Tretinoin (0.05% cream vs. 5% peel) for photoaging and field cancerization of the forearms: randomized, evaluator-blinded, clinical trial.

BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.

Surface wipe and bulk sampling of household dust: arsenic exposure in Cornwall, UK.

Dust elemental levels can be expressed as concentrations (bulk samples) or surface loadings (wipe samples). Wipe sampling has not been widely adopted for elements other than lead (Pb). In this study, 433 wipe samples from 130 households in south west England - a region of widespread, natural and anthropogenic arsenic contamination linked with previous mining activities-were analysed to (i) quantify loadings of arsenic (As); (ii) assess the quality of wipe data using QA/QC criteria; (iii) estimate, using published ingestion rates, human exposure to As in dust using loadings and concentrations from 97 bulk samples and (iv) comparatively assess the performance of wipe and bulk sampling using associations with As biomonitoring data (urine, toenails and hair). Good QC performance was observed for wipes: strong agreement between field duplicates, non-detectable contamination of field blank wipes and good reference material recoveries. Arsenic loadings exceeded an existing urban background benchmark in 67 (52%) households. No exceedances of tolerable daily As intake were observed for adult exposure estimates but infant estimates exceeded for 1 household. Infant estimates calculated using bulk concentrations resulted in 4 (3%) exceedances. Neither wipe nor bulk As metrics were sufficiently better predictors of As in biospecimens. Sampling strategies, analytical protocols, exposure metrics and assessment criteria require refinement to validate dust sampling methodologies.

Estudio radiográfico de la asociación de antioxidantes y bifosfonatos en remodelación ósea peri-Implantaria / Radiographic antioxidants association and biphosphonates study in bone remodeling peri-implant

Estudios previos han demostrado que los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) es rico en ácidos grasos monoinsaturados con potentes propiedades anti-oxidantes. El objetivo de este estudio fue estudiar el efecto del tratamiento de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración tisular. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/ Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100g de peso corporal de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. La cirugía consistió en una incisión longitudinal en las tibias realizando un defecto circular en la parte plana de cada tibia hasta llegar al hueso medular. Se tomaron radiografías a los 0, 7, 15, 30, 60 y 90 días y fueron analizadas con el Software Image Pro Plus. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Se evidencio un incremento en la densidad mineral ósea promedio (DMO) conforme avanza el tiempo en todos los grupos, siendo evidentes con PA a los 60 días. El tratamiento O mostró eficacia en la remodelación ósea, observándose un pico a los 60 días. Esto sugiere que O representa una opción terapéutica para el tratamiento de las patologías óseas.

Previous studies have shown that bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) is rich in monounsaturated fatty acids with potent anti-oxidant properties. The objective of this work was to study the effect of alendronate treatment (AL) and pamidronate (PA) and O on tissue regeneration. Formulas 0.5 mg / kg for AL dosed, and 0.6 mg / kg for PA. O was administered in the diet, 50 g / kg. Fifty-four male rats Wistar were divided into 6 groups. The control group (C) received weekly 0.3 ml / 100g body weight of saline subcutaneously. The group (AL) received a weekly dose subcutaneously in the left posterior limb. The group (PA) was placed as the previous group. The group (O) was treated in food and in the areas of surgery received subcutaneousinjection with saline. The group (ALO) received combined treatment with Al and O. The group (PAO) was treated the same as before. Surgery consisted of a longitudinal incision in the warm using a circular on the flat side of each tibia until the medullary bone defect. X-rays at 0, 7, 15, 30, 60 and 90 days were taken and analyzed with Image Pro Plus Software. Statistical studies were conducted through analysis of variance to two and three classification criteria. Results: an increase in the average bone mineral density (BMD) was evident as time progresses in all groups, with PA still evident at 60 days. Or treatment showed efficacy in bone remodeling observed a peak at 60 days. Conclusions: This suggests that O represents a therapeutic option for the treatment of bone disease.

Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK.

Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 µg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 µg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman's ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-As(IMM), of urinary inorganic As species, arsenite (As(III)) and arsenate (As(V)), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman's ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

Prolonged exposure to arsenic in UK private water supplies: toenail, hair and drinking water concentrations.

Chronic exposure to arsenic (As) in drinking water is an established cause of cancer and other adverse health effects. Arsenic concentrations >10 µg L(-1) were previously measured in 5% of private water supplies (PWS) in Cornwall, UK. The present study investigated prolongued exposure to As by measuring biomarkers in hair and toenail samples from 212 volunteers and repeated measurements of As in drinking water from 127 households served by PWS. Strong positive Pearson correlations (rp = 0.95) indicated stability of water As concentrations over the time period investigated (up to 31 months). Drinking water As concentrations were positively correlated with toenail (rp = 0.53) and hair (rp = 0.38) As concentrations - indicative of prolonged exposure. Analysis of washing procedure solutions provided strong evidence of the effective removal of exogenous As from toenail samples. Significantly higher As concentrations were measured in hair samples from males and smokers and As concentrations in toenails were negatively associated with age. A positive association between seafood consumption and toenail As and a negative association between home-grown vegetable consumption and hair As was observed for volunteers exposed to <1 As µg L(-1) in drinking water. These findings have important implications regarding the interpretation of toenail and hair biomarkers. Substantial variation in biomarker As concentrations remained unaccounted for, with soil and dust exposure as possible explanations.

Variability in the chemistry of private drinking water supplies and the impact of domestic treatment systems on water quality.

Tap water from 497 properties using private water supplies, in an area of metalliferous and arsenic mineralisation (Cornwall, UK), was measured to assess the extent of compliance with chemical drinking water quality standards, and how this is influenced by householder water treatment decisions. The proportion of analyses exceeding water quality standards were high, with 65 % of tap water samples exceeding one or more chemical standards. The highest exceedances for health-based standards were nitrate (11 %) and arsenic (5 %). Arsenic had a maximum observed concentration of 440 µg/L. Exceedances were also high for pH (47 %), manganese (12 %) and aluminium (7 %), for which standards are set primarily on aesthetic grounds. However, the highest observed concentrations of manganese and aluminium also exceeded relevant health-based guidelines. Significant reductions in concentrations of aluminium, cadmium, copper, lead and/or nickel were found in tap waters where households were successfully treating low-pH groundwaters, and similar adventitious results were found for arsenic and nickel where treatment was installed for iron and/or manganese removal, and successful treatment specifically to decrease tap water arsenic concentrations was observed at two properties where it was installed. However, 31 % of samples where pH treatment was reported had pH < 6.5 (the minimum value in the drinking water regulations), suggesting widespread problems with system maintenance. Other examples of ineffectual treatment are seen in failed responses post-treatment, including for nitrate. This demonstrates that even where the tap waters are considered to be treated, they may still fail one or more drinking water quality standards. We find that the degree of drinking water standard exceedances warrant further work to understand environmental controls and the location of high concentrations. We also found that residents were more willing to accept drinking water with high metal (iron and manganese) concentrations than international guidelines assume. These findings point to the need for regulators to reinforce the guidance on drinking water quality standards to private water supply users, and the benefits to long-term health of complying with these, even in areas where treated mains water is widely available.

Comparison of the Sofia and Veritor direct antigen detection assay systems for identification of influenza viruses from patient nasopharyngeal specimens.

Influenza antigen detection assays (Sofia fluorescent immunoassay [FIA] and Veritor) yield objective results, which are potentially useful for point-of-care testing. The assays were evaluated with reverse transcriptase PCR (RT-PCR) using 411 nasopharyngeal swab specimens. Sensitivity and specificity values (percentages) of 79.0/99.0 and 64.0/99.4 for influenza A and 92.9/96.7 and 78.6/98.7 for influenza B were obtained for the Sofia and Veritor assays, respectively.

Silicone/vegetable oil Janus emulsion: topological stability versus interfacial tensions and relative oil volumes.

Several aspects were studied of the formation and destabilization in bulk of silicone/vegetable oil, SO/VO, Janus emulsions, stabilized by Tween 80. In the formation of the emulsions, it was unexpectedly found that the dispersions tended to contain both single and flocculated drops irrespective of the emulsification intensity. Microscopy of the emulsions with no cover glass revealed flocculated drops of a large (200-500 µm) central SO drop with many small VO drops attached. Applying a cover glass did not significantly change the drop size; instead two-oil Janus drops of well-defined contact angle were found. The emulsions showed rapid creaming irrespective of the preparation method, but a few days storage did not significantly change the drop size in the creamed layer, nor was separation of the oils detected. The total interfacial free energy of the Janus drops at equilibrium was compared to the two relevant alternatives; engulfed and separate drops. The Janus drop free energies were found less for all volume ratios of the oils, when the surfactant concentrations in the aqueous phase was sufficient to prevent spreading of VO on SO. Changing the surfactant concentration to bring the interfacial tensions closer to the critical value for spreading gave declining interfacial free energy difference to that of engulfed drops.

Evaluation of respiratory syncytial virus (RSV) direct antigen detection assays for use in point-of-care testing.

RSV infections cause lower respiratory tract infections and result in surges in physician's office, emergency department visits and hospitalizations, especially in infants and toddlers. Point-of-care (POC) testing reduces healthcare costs and permits informed decisions on treatment, however, optimal POC assays must be sensitive, easy to perform and provide rapid results. A prospective study tested 230 patient nasopharyngeal specimens using 4 RSV direct antigen detection assays (Directigen, Quickvue, Sofia and Veritor) and RT-PCR. A RSV dilution study was also performed to evaluate sensitivity. RSV fluorescent antibody testing in 46/230 patients was also evaluated. Sensitivity values obtained for the Sofia, Veritor, Directigen and Quickvue assays (%) were 85, 72.5, 70 and 57.5, respectively. Fluorescent result interpretation may account for Sofia's enhanced sensitivity. Specificity (%) was 97-100 among assays. Sensitivity data were confirmed in the dilution studies. Fluorescent antibody testing demonstrated 64% sensitivity compared with RT-PCR. Objective result reporting, walk away testing and high sensitivity make the Sofia a valuable choice for POC testing. Veritor's sensitivity may also render it acceptable in POC. Lack of objective results by Directigen and the poor sensitivity observed by Quickvue may preclude their value in diagnostic testing.

Preparedness for a major incident: creation of an epidemiology protocol for a health protection register in England.

Large incidents and natural disasters are on the increase globally. They can have a major impact lasting many years or decades; and can affect large groups of people including those that are more susceptible to adverse consequences. Following a major incident, it may be considered necessary to establish a register of those people affected by the incident to provide appropriate advice on relevant immediate and longer-term public health interventions that may be required, provide reassurance to the public that their care is paramount, to reassure the worried well to avoid them inappropriately overwhelming local services, and to facilitate epidemiological investigations. Arrangements for the prompt follow-up of populations after large incidents or disasters have been agreed in England and a protocol for establishing a register of individuals potentially affected by a large incident has been developed. It is important for countries to have a protocol for implementing a health register if the circumstances require one to be in place, and are supported by Public Health Authorities. Health registers facilitate the initial descriptive epidemiology of exposure and provide the opportunity of carrying out long term analytical studies on the affected population. Such epidemiological studies provide a greater understanding of the impact that a large incident can have on health, which in turn helps in the planning of health care provision. Registers can also assist more directly in providing access to individuals in need of physical and mental health interventions. The challenge that still remains is to formally pilot the register in the field and refine it based on that experience.

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.