Mapping of Family Reported Outcome Measure (FROM-16) scores to EQ-5D: algorithm to calculate utility values.

OBJECTIVE: Although decision scientists and health economists encourage inclusion of family member/informal carer utility in health economic evaluation, there is a lack of suitable utility measures comparable to patient utility measures such those based on the EQ-5D. This study aims to predict EQ-5D-3L utility values from Family Reported Outcome Measure (FROM-16) scores, to allow the use of FROM-16 data in health economic evaluation when EQ-5D data is not available. METHODS: Data from 4228 family members/partners of patients recruited to an online cross-sectional study through 58 UK-based patient support groups, three research support platforms and Welsh social services departments were randomly divided five times into two groups, to derive and test a mapping model. Split-half cross-validation was employed, resulting in a total of ten multinomial logistic regression models. The Monte Carlo simulation procedure was used to generate predicted EQ-5D-3L responses, and utility scores were calculated and compared against observed values. Mean error and mean absolute error were calculated for all ten validation models. The final model algorithm was derived using the entire sample. RESULTS: The model was highly predictive, and its repeated fitting using multinomial logistic regression demonstrated a stable model. The mean differences between predicted and observed health utility estimates ranged from 0.005 to 0.029 across the ten modelling exercises, with an average overall difference of 0.015 (a 2.2% overestimate, not of clinical importance). CONCLUSIONS: The algorithm developed will enable researchers and decision scientists to calculate EQ-5D health utility estimates from FROM-16 scores, thus allowing the inclusion of the family impact of disease in health economic evaluation of medical interventions when EQ-5D data is not available.

GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients.

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Effects of Videos and Therapeutic Music on Preoperative Anxiety and Postoperative Anxiety and Pain Levels in Boys Who Undergo Circumcision.

PURPOSE: This purpose of this study was to investigate the effects of having boys aged 5 to 10 years who will undergo circumcision surgery watch informative videos and listen to therapeutic music on preoperative anxiety, and postoperative anxiety, pain, and nausea and vomiting. DESIGN: This was a prospective and ranomized controlled study. MATERIALS AND METHODS: The sample consisted of 90 boys aged 5 to 10 years who underwent circumcision surgery. The boys included in the study were randomly divided into 3 groups of 30 using a computer program. The first group (group V) watched the video; the second group (group M) listened to the music, and the third group (group C) was the control group with usual care. Boys and their parents were not blinded to the grouping. FINDINGS: Heart rate.ßvalues were found to be statistically significantly lower compared to the control group at the 1st minute after local anesthesia in group V (P.ß=.ß.029), at the 5th minute after local anesthesia in group M (P.ß=.ß.030), and at the 10th minute after local anesthesia and after the surgery in both group V and group M (P.ß=.ß.001 and P.ß=.ß.010, respectively). Wong-Baker Faces Pain Rating Scale.ßscores of the control group measured at the 2nd postoperative hour were found to be significantly higher than those of group V (P.ß=.ß.018). Children's Fear Scale.ßscores of group V measured at the time of admission to the postoperative service were found to be significantly higher than those of group M and group C (P.ß<.ß.001). There was no significant difference between the groups in terms of additional analgesic use, nausea and vomiting percentages, and time to discharge. CONCLUSIONS: The results of this study revealed that having boys aged 5 to 10 years who will undergo circumcision surgery watch informative videos and listen to therapeutic music did not have any significant effect on their postoperative pain, fear, and anxiety levels. Further large-scale studies, which will also include children who will not undergo circumcision surgery, are needed to generalize this study's results to larger populations.

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy.

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Crosstalk between primary and secondary metabolism: Interconnected fatty acid and polyketide biosynthesis in prokaryotes.

In primary metabolism, fatty acid synthases (FASs) biosynthesize fatty acids via sequential Claisen-like condensations of malonyl-CoA followed by reductive processing. Likewise, polyketide synthases (PKSs) share biosynthetic logic with FAS which includes utilizing the same precursors and cofactors. However, PKS biosynthesize structurally diverse, complex secondary metabolites, many of which are pharmaceutically relevant. This digest covers examples of interconnected biosynthesis between primary and secondary metabolism in fatty acid and polyketide metabolism. Taken together, further understanding the biosynthetic linkage between polyketide biosynthesis and fatty acid biosynthesis may lead to improved discovery and production of novel drug leads from polyketide metabolites.

N-acetyl-L-leucine for Niemann-Pick type C: a multinational double-blind randomized placebo-controlled crossover study.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as progressive cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded phase IIb clinical trial. Here, we describe the development of a study protocol (Sponsor Code "IB1001-301") for the chronic treatment of symptoms in adult and pediatric patients with NPC. METHODS: This multinational double-blind randomized placebo-controlled crossover phase III study will enroll patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites. Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments. DISCUSSION: Pre-clinical as well as observational and phase IIb clinical trials have previously demonstrated that IB1001 rapidly improved symptoms, functioning, and quality of life for pediatric and adult NPC patients and is safe and well tolerated. In this placebo-controlled cross-over trial, the risk/benefit profile of IB1001 for NPC will be evaluated. It will also give information about the applicability of IB1001 as a therapeutic paradigm for other rare and common neurological disorders. TRIAL REGISTRATIONS: The trial (IB1001-301) has been registered at www. CLINICALTRIALS: gov (NCT05163288) and www.clinicaltrialsregister.eu (EudraCT: 2021-005356-10). Registered on 20 December 2021.

Golfers have greater preoperative and equal postoperative function when undergoing total knee arthroplasty compared to non-golfers.

BACKGROUND: Approximately 10% to 20% of patients with joint arthroplasties are golfers. The aim of this study was to assess if being a golfer is associated with functional outcomes, satisfaction or improvement in quality of life (QoL) compared to non-golfers following total knee arthroplasty. METHODS: All patients undergoing primary total knee arthroplasty (TKA) over a one-year period at a single institution were included with one-year postoperative outcomes. Patients were retrospectively followed up to assess if they had been golfers at the time of their surgery. Multivariate linear regression analysis was performed to assess the independent association of preoperative golfing status on postoperative function and health-related outcomes. RESULTS: The study cohort consisted of a total of 514 patients undergoing TKA. This included 223 (43.3%) male patients and 291 (56.7%) female patients, with an overall mean age of 70 (SD 9.5) years. The preoperative Oxford Knee Score (OKS) was significantly higher in golfers when adjusting for confounders (Diff 3.4 [95% CI 1 to 5.8], p = 0.006). There was no difference in postoperative outcomes between golfers and non-golfers. There was however a trend towards a higher Forgotten Joint Score (FJS) in the golfers (difference 9.3, 95% CI - 0.2 to 18.8, p = 0.056). Of the 48 patients who reported being golfers at the time of their surgery, 43 (89.6%) returned to golf and 88.4% of those were satisfied with their involvement in golf following surgery. CONCLUSIONS: Golfers had better preoperative and equal postoperative knee specific function compared to non-golfers. The majority of golfers returned to golf by one year and were satisfied with their involvement in the game. LEVEL OF EVIDENCE: III.

Strategies to expand corporate autonomy by the tobacco, alcohol and sugar-sweetened beverage industry: a scoping review of reviews.

BACKGROUND: Noncommunicable diseases contribute to over 70% of global deaths each year. Efforts to address this epidemic are complicated by the presence of powerful corporate actors. Despite this, few attempts have been made to synthesize existing evidence of the strategies used to advance corporate interests across industries. Given this, our study seeks to answer the questions: 1) Is there an emergent taxonomy of strategies used by the tobacco, alcohol and sugar-sweetened beverage (SSB) industries to expand corporate autonomy? 2) How are these strategies similar and how are they different? METHODS: Under the guidance of a framework developed by Arksey and O'Malley, a scoping review was carried out whereby six databases were searched in June 2021 to identify relevant peer-reviewed literature. To be included in this review, studies had to explicitly discuss the strategies used by the tobacco, alcohol, and/or sugar-sweetened beverage multinational corporations and be considered review articles aimed to synthesize existing evidence from at least one of the three industries. Eight hundred and fifty-eight articles were selected for full review and 59 articles were retained for extraction, analysis, and categorization. RESULTS: Results identified six key strategies the industries used: 1) influencing government policy making and implementation, 2) challenging unfavorable science, 3) creating a positive image, 4) manipulating markets, 5) mounting legal challenges, and 6) anticipating future scenarios. Despite these similarities, there are few but important differences. Under the strategy of influencing government policy making and implementation, for example, literature showed that the alcohol and SSB industries have been "privileged with high levels of participation" within international public health organizations. CONCLUSIONS: Understanding how industries resist efforts to control them is important for public health advocates working to reduce consumption of and death and diseases resulting from harmful commodities. Moreover, there is a greater need for the public health community to generate consensus about how to ethically engage or not engage with industries that produce unhealthy commodities. More studies are also needed to build the evidence base of industry tactics to resist regulation, particularly in the case of SSB, and in low-and middle-income countries.

A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia.

BACKGROUND: The lack of approved treatments for the majority of rare diseases is reflective of the unique challenges of orphan drug development. Novel methodologies, including new functionally relevant endpoints, are needed to render the development process more feasible and appropriate for these rare populations and thereby expedite the approval of promising treatments to address patients' high unmet medical need. Here, we describe the development of an innovative master protocol and primary outcome assessment to investigate the modified amino acid N-acetyl-L-leucine (Sponsor Code: IB1001) in three separate, multinational, phase II trials for three ultra-rare, autosomal-recessive, neurodegenerative disorders: Niemann-Pick disease type C (NPC), GM2 gangliosidoses (Tay-Sachs and Sandhoff disease; "GM2"), and ataxia telangiectasia (A-T). METHODS/DESIGN: The innovative IB1001 master protocol and novel CI-CS primary endpoints were developed through a close collaboration between the Industry Sponsor, Key Opinion Leaders, representatives of the Patient Communities, and National Regulatory Authorities. As a result, the open-label, rater-blinded study design is considerate of the practical limitations of recruitment and retention of subjects in these ultra-orphan populations. The novel primary endpoint, the Clinical Impression of Change in Severity© (CI-CS), accommodates the heterogenous clinical presentation of NPC, GM2, and A-T: at screening, the principal investigator appoints for each patient a primary anchor test (either the 8-m walk test (8MWT) or 9-hole peg test of the dominant hand (9HPT-D)) based on his/her unique clinical symptoms. The anchor tests are videoed in a standardized manner at each visit to capture all aspects related to the patient's functional performance. The CI-CS assessment is ultimately performed by independent, blinded raters who compare videos of the primary anchor test from three periods: baseline, the end of treatment, and the end of a post-treatment washout. Blinded to the time point of each video, the raters make an objective comparison scored on a 7-point Likert scale of the change in the severity of the patient's neurological signs and symptoms from video A to video B. To investigate both the symptomatic and disease-modifying effects of treatment, N-acetyl-L-leucine is assessed during two treatment sequences: a 6-week parent study and 1-year extension phase. DISCUSSION: The novel CI-CS assessment, developed through a collaboration of all stakeholders, is advantageous in that it better ensures the primary endpoint is functionally relevant for each patient, is able to capture small but meaningful clinical changes critical to the patients' quality of life (fine-motor skills; gait), and blinds the primary outcome assessment. The results of these three trials will inform whether N-acetyl-L-leucine is an effective treatment for NPC, GM2, and A-T and can also serve as a new therapeutic paradigm for the development of future treatments for other orphan diseases. TRIAL REGISTRATION: The three trials (IB1001-201 for Niemann-Pick disease type C (NPC), IB1001-202 for GM2 gangliosidoses (Tay-Sachs and Sandhoff), IB1001-203 for ataxia telangiectasia (A-T)) have been registered at www.clinicaltrials.gov (NCT03759639; NCT03759665; NCT03759678), www.clinicaltrialsregister.eu (EudraCT: 2018-004331-71; 2018-004406-25; 2018-004407-39), and https://www.germanctr.de (DR KS-ID: DRKS00016567; DRKS00017539; DRKS00020511).

Local Anesthetic Systemic Toxicity (LAST): Increasing Awareness Through Education.

PURPOSE: Local anesthetics are used for procedures in various settings. Although complications related to local anesthetic use is rare, adverse events do occur. A significant knowledge deficit was identified regarding local anesthetic systemic toxicity (LAST) signs, symptoms, and treatment. DESIGN: A learning needs assessment was performed at a local hospital to determine the nurses' baseline knowledge of LAST signs, symptoms, and treatment. METHODS: A self-paced web-based learning module was developed and completed by clinical nurses with an immediate post survey and 6-month follow-up survey. FINDINGS: The repeat learning needs assessment immediately after education resulted in more than 50% improvement in nurses' knowledge of LAST. A 6-month follow-up survey indicated that the gain in knowledge, signs, symptoms, and treatment of LAST was maintained. CONCLUSIONS: An educational gap was identified regarding clinical nurses' knowledge of LAST. An educational program was designed to improve baseline knowledge. The program goal was successfully met with more than half of nurses being able to identify signs, symptoms, and treatment of LAST.

Availability and advertising of electronic cigarettes in two Russian cities following implementation of comprehensive tobacco advertising restrictions.

INTRODUCTION: Electronic cigarettes (e-cigarettes) continue to gain popularity globally. Jurisdictions with comprehensive tobacco control policies, which limit the use and availability of combustible tobacco products but do not regulate e-cigarettes (as in Russia), may be vulnerable to the expansion of the e-cigarette market. METHODS: Using McNemar's test conducted in STATA, this observational study assessed changes between 2014 and 2016 in the availability of e-cigarettes across 239 retail outlets in Moscow and St Petersburg. Also, this study characterized the presence of retail advertising and promotion of e-cigarettes in 2016. RESULTS: Between 2014 and 2016, the availability and display of e-cigarettes increased within traditional tobacco product retail venues (27.6% in 2014 vs 51.9% in 2016; p<0.01). CONCLUSIONS: Observations indicate that there has been an increase in the proportion of retailers selling and displaying e-cigarettes.

Synovial fluid cell counts and its role in the diagnosis of paediatric septic arthritis.

PURPOSE: Clinical presentation of paediatric septic arthritis (SA) can be similar to other joint pathologies. Despite potential for infection in all major joints, most diagnostic criteria are based on values from the hip. This study identifies the best joint aspirate values in diagnosing SA in all joints. METHODS: In all, 166 patients who underwent 172 joint aspirations at the authors' institution between 01 September 2004 and 01 September 2014 were retrospectively identified. Recorded measures included age, sex, duration of symptoms, fever history, weight-bearing status, aspiration results, serum results and antibiotic administration. Patients were placed in the following four categories: 'culture confirmed SA' (C-SA), 'suspected SA' (S-SA), 'Other' and 'Other-rheumatologic' (Other-R), a subcategory of 'Other'. RESULTS: Most common sites of aspiration were the knee (55%) and hip (29%). Diagnostic grouping was as follows: C-SA = 44, S-SA = 45, Other = 83 (Other-R = 21). Fever and non-weight-bearing prior to admission were useful predictors of SA, though in C-SA patients, 21% did not have a fever and 23% could weight bear at the time of admission. Aspirate white blood cell (WBC) count was significantly greater in both C-SA (92 000 cells/hpf) and S-SA (54 000) than in Other (10 000) and Other-R (18 000) patients. The percentage of polymorphonuclear (%PMN) was also significantly greater in C-SA (81.1%) and S-SA (80.9%) than in Other (57.9%) and Other-R (63.3%). CONCLUSION: Joint aspirate values, especially %PMN, are valuable in diagnosing SA. Additionally, antibiotics pre-aspiration did not affect %PMN, facilitating subsequent diagnosis of infection. Lastly, while aspirate WBC count was a valuable indicator of SA, this finding is not as definitive as previous research suggests. LEVEL OF EVIDENCE: IV Case Series.

Effects of post-scenario debriefing versus stop-and-go debriefing in medical simulation training on skill acquisition and learning experience: a randomized controlled trial.

BACKGROUND: Debriefing is a critical component to promote effective learning during simulation-based training. Traditionally, debriefing is provided only after the end of a scenario. A possible alternative is to debrief specific portions during an ongoing simulation session (stop-and-go debriefing). While this alternative has theoretical advantages, it is not commonly used due to concerns that interruptions disturb the fidelity and adversely affect learning. However, both approaches have not been rigorously compared, and effects on skill acquisition and learning experience are unknown. METHODS: We randomly assigned 50 medical students participating in a simulation-based cardiopulmonary resuscitation training to either a post-scenario debriefing or stop-and-go debriefing. After four weeks, participants performed a repeat scenario, and their performance was assessed using a generic performance score (primary outcome). A difference of 3 or more points was considered meaningful. A 5-item questionnaire was used to assess the subjective learning experience and the perceived stress level (secondary outcomes). RESULTS: There was no significant difference between the groups for the performance score (mean difference: -0.35, 95%CI: -2.46 to 1.77, P = 0.748, n = 48). The confidence limits excluding the specified relevant 3-point difference suggest equivalence of both techniques with respect to the primary outcome. No significant differences were observed for secondary outcomes. CONCLUSIONS: Stop-and-go debriefing does not adversely affect skill acquisition compared to the classic post-scenario debriefing strategy. This finding is reassuring when interruptions are deemed necessary and gives simulation instructors the latitude to tailor the timing of the debriefing individually, rather than adhering to the unsupported dogma that scenarios should not be interrupted. TRIAL REGISTRATION: As this study is not a clinical trial, it was not registered in a clinical trials register.

Optimizing pharmaceutical care for pediatric patients with dermatitis: perspectives of parents and pharmacy staff.

Background Atopic dermatitis affects 10-20% of the children worldwide. Unfortunately not all patients who receive treatment have optimal treatment outcomes. Objective To assess the view of parents and pharmacy staff in order to optimize pharmaceutical care for young atopic dermatitis patients. Setting Community pharmacies in the Netherlands. Method We first held an expert panel meeting to determine experts' views on treatment of atopic dermatitis and their suggestions for areas of improvement. This input was used to develop the interview guide. We conducted telephone interviews with parents of children (aged 0-12 years) with atopic dermatitis and face-to-face interviews with pharmacy staff members. All interviews were audiotaped and transcribed verbatim. Transcripts were coded using qualitative data analysis software. Codes were used to identify themes. Main outcome measure Perspectives of parents of young atopic dermatitis patients and pharmacy staff about treatment. Results We interviewed 29 parents and 18 pharmacy staff members. Many parents mentioned fear of steroid adverse effects, with intentional nonadherence as a consequence, and difficulties with the application of topical treatment. Pharmacy employees also mentioned to encounter these issues. Some employees themselves expressed concerns towards use of steroids. Most parents were satisfied with the information they received; however, they need more practical lifestyle advices, e.g. about bathing or clothing. Both pharmacists and pharmacy technicians mentioned that technicians often lack knowledge to support patients optimally in correct medication use. Conclusion Parents' perceptions about topical corticosteroids might negatively influence treatment outcomes. Pharmacy staff has an important role to inform parents of children with eczema on the appropriate use of topical corticosteroids and emollients. Counseling should not be influenced by their own prejudices about topical corticosteroids. Close collaboration between primary care providers should ensure that parents receive uniform messages.

Impact of tranexamic acid use on blood loss and transfusion rates following femoral varus derotational osteotomy in children with cerebral palsy.

PURPOSE: Previous studies have established the safety and efficacy of tranexamic acid (TXA) in reducing blood loss after total joint arthroplasty and spinal fusion surgery; however, literature regarding the effectiveness of intraoperative TXA in children with cerebral palsy (CP) is limited. The aim of this study was to investigate the safety and efficacy of intraoperative TXA in reducing blood loss and transfusion requirements for children with CP undergoing a proximal femoral varus derotational osteotomy (VDRO). METHODS: This is a retrospective review of 258 children with CP who underwent VDRO performed at the author's institution between 2004 and 2017. In all, 36 subjects underwent VDRO surgery with administration of intravenous TXA and 222 subjects underwent VDRO without administration of TXA. Outcome measures including blood loss, transfusion requirements and venous thromboembolic events were compared between groups using t-tests and chi-squared tests. RESULTS: No significant differences were seen in the rates of transfusion between groups for the entire hospitalization (TXA group: 11.1% versus No TXA group: 19.8%), intraoperatively (TXA: 2.8% versus No TXA: 9.0%) or postoperatively (TXA: 8.3% versus No TXA: 14.4%). Intraoperative estimated blood loss (TXA: 144.4 mL versus No TXA: 159.0 mL) and percentage blood loss (TXA: 8.9% versus No TXA: 9.2%) were similar between groups. No major thromboembolic complications events occurred in either group. CONCLUSION: The use of TXA was not associated with thromboembolic complications in this series of children with CP undergoing VDRO surgery. Though there was a trend toward lower rates of intraoperative and postoperative blood transfusion with TXA use in these patients, the differences were not significant, possibly due to low estimated blood loss in both groups and sample size. LEVEL OF EVIDENCE: III- retrospective comparative study.

"Decide Now, Buy Marlboro": Examining the influence and appeal of Marlboro's new brand architecture among Filipino adolescents.

In recent years, Philip Morris International (PMI) launched a global rebranding strategy to expand the reach of Marlboro. Using a mixed-methods design, this study evaluated the appeal and influence of Marlboro advertising among Filipino youth. Six hundred and twenty-three adolescents aged 13-17 years old in Metro Manila participated in a survey, including three advertising conditions: two for Marlboro and one for Mighty, a local cigarette brand. One-way repeated measures analysis of variance (ANOVA) and paired t-tests evaluated differences between the three conditions on participants' attitudes toward advertisements [measured as identification, likeability, and perceived effectiveness (PE)]. Compared to Mighty, never-smokers rated Marlboro advertisements as more identifiable and likeable. Comparing by smoking status (never vs. ever), multivariable logistic regression assessed the influence of these attitudes on intention to smoke. Increased likeability was associated with greater intention to smoke among never-smokers, and greater PE increased odds of intention to smoke for both never- and ever-smokers. Additionally, six focus group discussions (FGD) explored responses to campaign messaging. Themes were compared within and across groups. Marlboro was also appealing to FGD participants, who described the ads as attractive to youth and promoting "adventure" and "freedom", whereas the Mighty brand was seen as being for adults and current smokers. Our findings illustrate that Marlboro advertisements are distinctly appealing to youth. Marlboro rhetoric - where consumers are urged to "decide" to "Be Marlboro" - was particularly powerful. These findings support the need for addressing gaps in policies regulating the marketing and promotion of tobacco in the Philippines.

Thermographic skin temperature measurement compared with cold sensation in predicting the efficacy and distribution of epidural anesthesia.

Due to the high rates of epidural failure (3-32%), novel techniques are required to objectively assess the successfulness of an epidural block. In this study we therefore investigated whether thermographic temperature measurements have a higher predictive value for a successful epidural block when compared to the cold sensation test as gold standard. Epidural anesthesia was induced in 61 patients undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic picture was recorded at 5, 10 and 15 min following epidural anesthesia induction. After 15 min a cold sensation test was performed. Epidural anesthesia is associated with a decrease in skin temperature. Thermography predicts a successful epidural block with a sensitivity of 54% and a PPV of 92% and a specificity of 67% and a NPV of 17%. The cold sensation test shows a higher sensitivity and PPV than thermography (97 and 93%), but a lower specificity and NPV than thermography (25 and 50%). Thermographic temperature measurements can be used as an additional and objective method for the assessment of the effectiveness of an epidural block next to the cold sensation test, but have a low sensitivity and negative predictive value. The local decrease in temperature as observed in our study during epidural anesthesia is mainly attributed to a core-to-peripheral redistribution of body heat and vasodilation.