Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Awareness of sun exposure risks and photoprotection for preventing pigmentary disorders in Asian populations: Survey results from three Asian countries and expert panel recommendations.

BACKGROUND: In this article, we review and discuss the photoprotection behavior of Asians based on the literature, along with a subanalysis of an original online survey, and make recommendations to optimize photoprotection for Asian populations to prevent photoaging and pigmentary disorders. METHODS: An international panel of eight dermatologists from Asia (China, Korea, Japan, Singapore, Indonesia, and Vietnam) met to discuss sunscreen photoprotection for Asian patients. Additionally, a subanalysis of an online survey by 3000 respondents from three Asian countries (China, Indonesia, and Japan) investigated general public awareness and attitudes to sun exposure. RESULTS: A pre-meeting survey of the eight experts from Asia showed key concerns of Asian patients consulting dermatologists are pigmentary disorders, especially actinic/senile lentigo, post-inflammatory hyperpigmentation, melasma, vitiligo, and Hori's nevus. The survey subanalysis of participants from China, Indonesia, and Japan with predominantly Fitzpatrick skin types (FST) II to IV revealed that they are particularly concerned about sun exposure causing photoaging and pigmentary disorders. Most of the respondents indicated they have limited knowledge on sunlight radiation and appropriate sunscreen protection factors. Only 22%, 13%, and 3% for China, Indonesia, and Japan, respectively, systematically use multiple protective measures (using sunscreen, avoiding midday sun, staying in the shade, wearing a hat, protective clothing, and sunglasses) when exposed to the sun. CONCLUSIONS: Further education is needed for Asian populations on the importance of comprehensive daily photoprotection, including broad-spectrum sunscreen, with high UVA and visible light protection, to reduce and prevent photoaging and pigmentary disorders.

Sun exposure behaviours as a compromise to paradoxical injunctions: Insight from a worldwide survey.

BACKGROUND: Behavioural interventions can improve attitudes towards sun protection but the impact remains inconsistent worldwide. OBJECTIVE: To assess awareness of and attitudes towards the multiple facets of sun exposure and suggest ways to improve prevention from overexposure to the sun in all geographical zones and multiple skin types. METHODS: Online survey was conducted from 28 September to 18 October 2021. Study population was selected from the Ipsos online Panel (3,540,000 panellists), aged ≥18 years, from 17 countries around the five continents. Demographics, sun-exposure habits and practices, understanding of risks and information on phototypes were documented and analysed using descriptive statistics. RESULTS: Eighty-eight per cent of participants knew that sunlight can cause skin health problems (90% phototypes I-II, 82% phototypes V-VI, >90% in American and European countries, 72% in Asia and 85% in Africa). Eighty-five per cent used some form of protection against sunlight, predominantly: Seeking shade (77%), avoiding the midday sun (66%), facial application of sunscreen (60%) and wearing protective clothing (44%). The perception of sunlight itself is positive ('it gives energy' for 82%; 'tanned skin looks attractive' for 72%), although less in Asian countries and among individuals with dark skin phototypes. Eighty-three per cent reported having experienced sunburn, mainly in Australia, Canada, USA, Germany, France and Russia, and among individuals with dark skin phototypes. Only 12% systematically/often used all types of protection during exposure to the sun and 23% believed it is safe to go out in the sun with no protection when their skin is already tanned. From 13% (skin phototype I) to 26% (phototype VI) reported not using any form of protection against the sun. Knowledge and habits were significantly superior among people who are accustomed to seeing a dermatologist for a complete skin exam. CONCLUSIONS: Dermatologists could play a crucial role in relaying novel prevention messages, more finely tailored to specific risks, populations and areas of the world.

Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU: A Study From the International Contact Dermatitis Research Group.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

Expert consensus on holistic skin care routine: Focus on acne, rosacea, atopic dermatitis, and sensitive skin syndrome.

BACKGROUND: Treatment, cleansing, moisturizing, and photoprotection are four major components of holistic skin care for dermatological conditions. While treatment (T) is recognized as a key component in the management of dermatological conditions, there is a lack of practical guidance on the adjunctive role of cleansing, moisturizing, and photoprotection ("CMP"). Limited patient knowledge, confusion over product selection, and lack of guidance on how to choose and use CMP skin care products (in conjunction with pharmacological therapy) are the main barriers to establishing a holistic skin care routine for dermatological conditions. AIMS: This study aimed to review current clinical evidence, identify gaps, and provide practical guidance on conceptualization and implementation of CMP routine in the management of sensitive skin due to underlying acne, atopic dermatitis, or rosacea, including conditions with idiopathic causes referred to as idiopathic sensitive skin syndrome. METHODS: An expert panel comprising of 10 dermatologists from Australia, China, Hong Kong, Taiwan, India, Indonesia, Philippines, Singapore, South Korea, and Thailand convened to develop consensus statements on holistic skin care in acne, rosacea, atopic dermatitis, and idiopathic sensitive skin syndrome using the Delphi approach. RESULTS: Consensus was defined as ≥80% of panel rating statement as ≥8 or median rating of ≥8. The final statements were collated to develop consensus recommendations on holistic skin care. CONCLUSION: A dermatologist-guided holistic skin care routine is essential to improve patient confidence and reduce confusion over product selection. The consensus recommendations presented here highlight the importance of cleansing, moisturization, and photoprotection in holistic skin care and how it can be utilized as a communication tool for physicians and patients to achieve overall better patient compliance, satisfaction, and treatment outcomes.

Transdermal Maltose-Based Microneedle Patch as Adjunct to Enhance Topical Anesthetic before Intravenous Cannulation of Pediatric Thalassemic Patients Receiving Blood Transfusion: A Randomized Controlled Trial Protocol.

Intravenous cannulation is experientially traumatic to children. To minimize this, EMLA® is applied on the would-be-cannulated area before IV cannula insertion. However, the time to achieve its maximum efficacy may be affected due to incomplete cutaneous absorption and the duration of application. The latter may be a limiting factor in a busy healthcare facility. The usage of dissolvable maltose microneedles may circumvent this problem by introducing micropores that will facilitate EMLA® absorption. A randomized phase II cross-over trial will be conducted to compare the Visual Analogue Scale (VAS) pain scores and skin conductance algesimeter index between 4 different interventions (1 fingertip unit (FTU) of EMLA® with microneedle patch for 30 min before cannulation; 0.5 FTU of EMLA® with microneedle patch for 30 min; 1 FTU of EMLA® with microneedle for 15 min; 1 FTU of EMLA® with sham patch for 30 min). A total of 26 pediatric patients with thalassemia aged between 6 and 18 years old and requiring blood transfusion will be recruited in this trial. During the visits, the VAS scores and skin conductance algesimeter index at venous cannulation will be obtained using the VAS rulers and PainMonitor™ machine, respectively. The trial will commence in August 2021 and is anticipated to end by August 2022.

Patch Testing With Nickel Sulfate 5.0% Traces Significantly More Contact Allergy Than 2.5%: A Prospective Study Within the International Contact Dermatitis Research Group.

BACKGROUND: Nickel allergy is the most common contact allergy, and a nickel salt is, therefore, included in most baseline patch test series. In the baseline series of the International Contact Dermatitis Research Group and the American Contact Dermatitis Society, nickel sulfate hexahydrate (NSH) in petrolatum at 2.5% is included, whereas NSH at 5.0% is included in many other baseline series, such as the European and Swedish ones. OBJECTIVE: The aim of the study is to investigate whether NSH at 5.0% detects significantly more contact allergy than NSH 2.5% when both preparations are tested simultaneously in consecutive dermatitis patients. PATIENTS AND METHODS: Two thousand two hundred eighty-seven consecutive dermatitis patients were patch tested simultaneously with NSH in petrolatum at 2.5% and 5.0%. The allergy rates were compared for all clinics individually and combined using McNemar test, 2-sided. RESULTS: Contact allergy to NSH 5.0% and 2.5% was found in 20.3% and 16.8%, respectively ( P < 0.0001). In 6 of 11 clinics, significantly more patients tested positive to the higher NSH concentration. For the 2 clinics in North America combined, significantly more patients tested positive to NSH 5.0%. CONCLUSIONS: The NSH preparation in the International Contact Dermatitis Research Group baseline patch test series should be considered to be changed from NSH 2.5% (1 mg NSH/cm 2 ) to 5.0% (2 mg NSH/cm 2 ).

Isotretinoin Laboratory Monitoring in Acne Treatment: A Delphi Consensus Study.

Importance: Although isotretinoin may rarely be associated with laboratory abnormalities such as hypertriglyceridemia, the optimal approach to laboratory monitoring is uncertain, and there is wide variation in clinical practice. Objective: To establish a consensus for isotretinoin laboratory monitoring among a diverse, international cohort of clinical and research experts in acne. Design, Setting, and Participants: Using a modified electronic Delphi process, 4 rounds of anonymous electronic surveys were administered from 2021 to 2022. For laboratory tests reaching consensus (≥70% agreement) for inclusion, questions regarding more time-specific monitoring throughout isotretinoin therapy were asked in subsequent rounds. The participants were international board-certified dermatologist acne experts who were selected on a voluntary basis based on involvement in acne-related professional organizations and research. Main Outcomes and Measures: The primary outcome measured was whether participants could reach consensus on key isotretinoin laboratory monitoring parameters. Results: The 22 participants from 5 continents had a mean (SD) time in practice of 23.7 (11.6) years and represented a variety of practice settings. Throughout the 4-round study, participation rates ranged from 90% to 100%. Consensus was achieved for the following: check alanine aminotransferase within a month prior to initiation (89.5%) and at peak dose (89.5%) but not monthly (76.2%) or after treatment completion (73.7%); check triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not monthly (84.2%) or after treatment completion (73.7%); do not check complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all >70%); do not check gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), low-density lipoprotein (73.7%), high-density lipoprotein (73.7%), or C-reactive protein (77.3%). Conclusions and Relevance: This Delphi study identified a core set of laboratory tests that should be evaluated prior to and during treatment with isotretinoin. These results provide valuable data to guide clinical practice and clinical guideline development to optimize laboratory monitoring in patients treated with isotretinoin.

Expert Recommendations on the Evaluation of Sunscreen Efficacy and the Beneficial Role of Non-filtering Ingredients.

A variety of non-filtering agents have been introduced to enhance sunscreen photoprotection. Most of those agents have only weak erythema protective properties but may be valuable and beneficial in supporting protection against other effects of UV radiation, such as photoimmunosuppression, skin aging, and carcinogenesis, as well as photodermatoses. The question arises how to measure and evaluate this efficacy since standard SPF testing is not appropriate. In this perspective, we aim to provide a position statement regarding the actual value of SPF and UVA-PF to measure photoprotection. We argue whether new or additional parameters and scales can be used to better indicate the protection conferred by these products against the detrimental effects of natural/artificial, UV/visible light beyond sunburn, including DNA damage, photoimmunosuppression and pigmentation, and the potential benefits of the addition of other ingredients beyond traditional inorganic and organic filters to existing sunscreens. Also, we debate the overall usefulness of adding novel parameters that measure photoprotection to reach two tiers of users, that is, the general public and the medical community; and how this can be communicated to convey the presence of additional beneficial effects deriving from non-filtering agents, e.g., biological extracts. Finally, we provide a perspective on new challenges stemming from environmental factors, focusing on the role of the skin microbiome and the role of air pollutants and resulting needs for photoprotection.

Mobile device: a useful tool to teach inhaler devices to healthcare professionals.

BACKGROUND: Proper inhaler device usage is paramount for control of underlying obstructive airway disease. Hence, education to healthcare professionals who will eventually educate patients need to be done effectively. We developed an application for mobile devices for education on six medical inhaler devices, the metered-dose inhaler (MDI), Turbuhaler, Accuhaler, Breezhaler, Ellipta and Respimat, and studied if there were any difference between the application and the manufacturer's instructions on inhaler technique. The aim of this study is to see if inhaler education via a mobile phone app is comparable to manual instruction for health care professions. METHODS: Participants, who were nursing students, were randomized to learn the inhaler devices via the manufacturer's instruction guide or a mobile device app designed specifically for education on inhaler devices. RESULTS: There were 45 participants in each group. 78% of them were females with a median age of 21 (IQR 3). 67% used an Apple mobile device and the remainder used an Android device. The mobile device showed better total improvement points for the Turbuhaler device (262 vs 287 points; P = 0.02). Participants learning from the manufacturer's guide had a significantly higher total improvement points in the Breezhaler (370 vs 327 points; P < 0.01) and Ellipta (214 vs 174 points; P < 0.01) device. Both interventions showed improvement in total scores for demonstrating the correct usage of all inhaler devices. MDI has the least number of correct steps for both interventions. The participants' reported their mean (SD) self-rated knowledge was significantly higher for those using the app for all devices as compared to those that did not (4.33 (0.68) vs 4.73 (0.42); P = < 0.01). Self-reported confidence level was found to be higher in the mobile app group, but this was not statistically significant. The app was well received and scored of 4.42 of 5 with regards to its quality. CONCLUSION: Using a mobile inhaler app is just as effective to teach inhaler device techniques to healthcare professionals and is likely a more convenient, versatile and important adjunct to learning. TRIAL REGISTRATION: National Healthcare Group Ethics Board (2018/00960).

A Review on the Combined Use of Soft Tissue Filler, Suspension Threads, and Botulinum Toxin for Facial Rejuvenation.

The aim of combining different minimally invasive techniques is to achieve the most harmonious and most natural-looking facial rejuvenation as effectively and as safely as possible. Due to their safety and versatility, botulinum toxin and soft tissue fillers have become the most sought-after modalities for correcting the signs of facial aging. Recently, bioabsorbable threads used for repositioning ptotic facial tissue have been added into the picture. More practitioners are also combining threads with fillers and botulinum toxin to achieve longer-lasting and natural-looking results. Our aim is to provide guidance on basic anatomical landmarks and areas where botulinum toxin injections, subcutaneous filler injections, and bioabsorbable suspension threads are placed on the face. We would also like to share our best practices on the best combination, spacing the appropriate time intervals in between each procedure to allow for the shortest possible recovery time, as well as periprocedural advice for an integrated treatment approach.

Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial.

BACKGROUND: Predict Prostate is a freely available online personalised risk communication tool for men with nonmetastatic prostate cancer. Its accuracy has been assessed in multiple validation studies, but its clinical impact among patients has not hitherto been assessed. OBJECTIVE: To assess the impact of the tool on patient decision-making and disease perception. DESIGN, SETTING, AND PARTICIPANTS: A multicentre randomised controlled trial was performed across eight UK centres among newly diagnosed men considering either active surveillance or radical treatment. A total of 145 patients were included between 2018 and 2020, with median age 67 yr (interquartile range [IQR] 61-72) and prostate-specific antigen 6.8 ng/ml (IQR 5.1-8.8). INTERVENTION: Participants were randomised to either standard of care (SOC) information or SOC and a structured presentation of the Predict Prostate tool. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Validated questionnaires were completed by assessing the impact of the tool on decisional conflict, uncertainty, anxiety, and perception of survival. RESULTS AND LIMITATIONS: Mean Decisional Conflict Scale scores were 26% lower in the Predict Prostate group (mean = 16.1) than in the SOC group (mean = 21.7; p = 0.027). Scores on the "support", "uncertainty", and "value clarity" subscales all favoured Predict Prostate (all p < 0.05). There was no significant difference in anxiety scores or final treatment selection between the two groups. Patient perception of 15-yr prostate cancer-specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower and more accurate among men in the Predict Prostate group (p < 0.001). In total, 57% of men reported that the Predict Prostate estimates for PCSM were lower than expected, and 36% reported being less likely to select radical treatment. Over 90% of patients in the intervention group found it useful and 94% would recommend it to others. CONCLUSIONS: Predict Prostate reduces decisional conflict and uncertainty, and shifts patient perception around prognosis to be more realistic. This randomised trial demonstrates that Predict Prostate can directly inform the complex decision-making process in prostate cancer and is felt to be useful by patients. Future larger trials are warranted to test its impact upon final treatment decisions. PATIENT SUMMARY: In this national study, we assessed the impact of an individualised risk communication tool, called Predict Prostate, on patient decision-making after a diagnosis of localised prostate cancer. Men were randomly assigned to two groups, which received either standard counselling and information, or this in addition to a structured presentation of the Predict Prostate tool. Men who saw the tool were less conflicted and uncertain in their decision-making, and recommended the tool highly. Those who saw the tool had more realistic perception about their long-term survival and the potential impact of treatment upon this. TAKE HOME MESSAGE: The use of an individualised risk communication tool, such as Predict Prostate, reduces patient decisional conflict and uncertainty when deciding about treatment for nonmetastatic prostate cancer. The tool leads to more realistic perceptions about survival outcomes and prognosis.

Expert Consensus on Soft-tissue Repositioning Using Absorbable Barbed Suspension Double-needle Threads in Asian and Caucasian Patients.

Bioabsorbable barbed suspension double-needle threads have recently been thrust into the limelight as a minimally invasive alternative for skin repositioning. When compared to surgical face lifting, use of these threads requires reduced procedural and recovery time, no general anesthesia, confers immediate patient satisfaction, with no cutaneous incisions and no apparent scars, and is more tolerable. There is currently limited literature providing clinical guidance on the use of these suspension threads; hence, this consensus document was developed as the first publication to discuss the technical aspects of facial rejuvenation using the double-needle barbed bioabsorbable and hydrolyzable thread composed of copolymer poly (ε-caprolactone-co-L-lactic acid) or PCxLyA, that is, Definisse threads. The Board of Aesthetic Leaders and Investigators (BALI) is a panel of dermatologic surgery and plastic surgery experts who convened last July 2018 in Indonesia to discuss the aforementioned challenges. A thorough literature search was done where a review of specific technical recommendations based on prevailing practice and available guidelines pertaining to suspension threads were described and are summarized in this paper. A detailed list of pretreatment recommendations in the assessment of both Asian and Caucasian facial types, aging facial types, guidance on insertion techniques, and aftercare instructions for clinicians to review has been included here.

Hierarchical HZSM-5 for Catalytic Cracking of Oleic Acid to Biofuels.

Solid acid catalyzed cracking of waste oil-derived fatty acids is an attractive route to hydrocarbon fuels. HZSM-5 is an effective acid catalyst for fatty acid cracking; however, its microporous nature is susceptible to rapid deactivation by coking. We report the synthesis and application of hierarchical HZSM-5 (h-HZSM-5) in which silanization of pre-crystallized zeolite seeds is employed to introduce mesoporosity during the aggregation of growing crystallites. The resulting h-HZSM-5 comprises a disordered array of fused 10-20 nm crystallites and mesopores with a mean diameter of 13 nm, which maintain the high surface area and acidity of a conventional HZSM-5. Mesopores increase the yield of diesel range hydrocarbons obtained from oleic acid deoxygenation from ~20% to 65%, attributed to improved acid site accessibility within the hierarchical network.

Patch Testing With a New Composition of the Mercapto Mix-A Multicenter Study from the International Contact Dermatitis Research Group.

BACKGROUND: Mercaptobenzothiazole compounds are associated with allergic contact dermatitis caused by rubber products. Several screening substances have been used for patch testing. OBJECTIVE: To compare the frequency of positive test reactions to a mercapto mix containing a higher concentration of 2-mercaptobenzothiazole with reactions to the combination of 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0%. METHODS: There were 7103 dermatitis patients in 12 International Contact Dermatitis Research Group dermatology departments who were patch tested with 2-mercaptobenzothiazole 2.0% petrolatum (pet.), mercapto mix 2.0% pet., and mercapto mix 3.5% pet. RESULTS: Contact allergy to the 3 test preparations varied among the 12 centers: 2-mercaptobenzothiazole 2.0% pet. (0-2.4%), mercapto mix 2.0% pet. (0-4.9%), and mercapto mix 3.5% pet. (0-1.4%). 2-Mercaptobenzothiazole 2.0% and mercapto mix 2.0% detected a few more positive patients compared with mercapto mix 3.5%, but the difference was statistically insignificant (mercapto mix 2.0% pet., P = 1.0; 2-mercapto-benzothiazole 2.0% pet., P = 0.66). CONCLUSIONS: Mercapto mix 3.5% pet. is not better than 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0% by a difference that is significant. By using only 1 test preparation (mercapto mix 3.5%), an additional hapten could be tested. No cases of suspected/proven patch test sensitization were registered.

Patch Testing With Methylchloroisothiazolinone/Methylisothiazolinone Using a New Diagnostic Mix-A Multicenter Study From the International Contact Dermatitis Research Group.

BACKGROUND: In the early 1980s, a preservative containing a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) in a ratio of 3:1 was introduced. This mixture (mix) has been patch tested at 100 ppm (0.01%) worldwide and at 200 ppm (0.02%) in Sweden since 1986 and also in the European baseline series since 2014. OBJECTIVE: A new aqueous mix of MCI 0.015% and MI 0.2% was compared with patch testing with the 2 aqueous baseline preparations of MCI/MI 0.02% and MI 0.2%. METHODS: Four thousand three hundred ninety-seven patients with dermatitis in 12 International Contact Dermatitis Research Group dermatology departments from 3 continents were patch tested simultaneously with the 3 preparations. RESULTS: The frequency of positive patch tests to the allergens varied between 0% and 26.7% in the 12 test centers. The new mixture MCI/MI 0.215% in aqua (aq) detected significantly more patients with MCI/MI allergy than both MCI/MI 0.02% aq (P < 0.001) and MI 0.2% aq (P < 0.001) alone and combined. CONCLUSIONS: The results favor replacing the preparations MCI/MI 0.02% aq and MI 0.2% aq with the mixture MCI/MI 0.215% aq in the International Contact Dermatitis Research Group baseline series.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.

BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.