(De-)centralized health care delivery, surgical outcome, and psychosocial health of transgender and gender-diverse people undergoing vaginoplasty: results of a retrospective, single-center study.

PURPOSE: Previous research on genital gender-affirming surgery lacked to build a framework that took various surrounding factors into account. E.g., transgender health care services are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). The present study investigated the effects of different structural and clinical aspects of gender-affirming genital surgery on psychosocial outcomes. METHODS: We surveyed former transgender and gender-diverse people who completed a vaginoplasty between 2014 and 2018. 45 participants were included in the study. We calculated hierarchical linear regression analyses to assess the relationship between psychosocial outcome measures (gender congruence, mental health, quality of life) and different aspects of gender-affirming genital surgery (e.g., setting of service delivery). To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identify predictors that are actually related to the outcomes. RESULTS: A non-responder analysis revealed no systematic bias in the recruitment procedure. Treatment satisfaction was a significant predictor for gender congruence. Moreover, we found the setting of service delivery (centralized, decentralized) to predict psychological health and the physical health dimension of quality of life. The effect sizes of our models were moderate to high, and models explained up to 26% of the total variance with a power up to 0.83. CONCLUSION: The present study is an exploratory attempt into the manifold relationships between treatment-related factors (e.g., aesthetic outcome), the setting of service delivery, and their effects on gender-affirming genital surgery.

Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.

BACKGROUND: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. METHODS: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. FINDINGS: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). INTERPRETATION: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. FUNDING: F Hoffmann-La Roche/Genentech.

Genders and Individual Treatment Progress in (Non-)Binary Trans Individuals.

BACKGROUND: Health care for transgender and transsexual (ie, trans) individuals has long been based on a binary understanding of gender (ie, feminine vs masculine). However, the existence of non-binary or genderqueer (NBGQ) genders is increasingly recognized by academic and/or health care professionals. AIM: To gain insight into the individual health care experiences and needs of binary and NBGQ individuals to improve their health care outcomes and experience. METHODS: Data were collected using an online survey study on experiences with trans health care. The non-clinical sample consisted of 415 trans individuals. An individual treatment progress score was calculated to report and compare participants' individual progress toward treatment completion and consider the individual treatment needs and definitions of completed treatment (ie, amount and types of different treatments needed to complete one's medical transition). OUTCOMES: Main outcome measures were (i) general and trans-related sociodemographic data and (ii) received and planned treatments. RESULTS: Participants reported binary (81.7%) and different NBGQ (18.3%) genders. The 2 groups differed significantly in basic demographic data (eg, mean age; P < .05). NBGQ participants reported significantly fewer received treatments compared with binary participants. For planned treatments, binary participants reported more treatments related to primary sex characteristics only. Binary participants required more treatments for a completed treatment than NBGQ participants (6.0 vs 4.0). There were no differences with regard to individual treatment progress score. CLINICAL TRANSLATION: Because traditional binary-focused treatment practice could have hindered NBGQ individuals from accessing trans health care or sufficiently articulating their needs, health care professionals are encouraged to provide a holistic and individual treatment approach and acknowledge genders outside the gender binary to address their needs appropriately. STRENGTHS AND LIMITATIONS: Because the study was made inclusive for non-patients and individuals who decided against trans health care, bias from a participant-patient double role was prevented, which is the reason the results are likely to have a higher level of validity than a clinical sample. However, because of the anonymity of an online survey, it remains unclear whether NBGQ individuals live according to their gender identity in their everyday life. CONCLUSION: The study highlights the broad spectrum of genders in trans-individuals and associated health care needs and provides a novel approach to measure individual treatment progress in trans individuals. Koehler A, Eyssel J, Nieder TO. Genders and Individual Treatment Progress in (Non-)Binary Trans Individuals. J Sex Med 2018;15:102-113.

Exploring the Relationship between (De-)Centralized Health Care Delivery, Client-Centeredness, and Health Outcomes-Results of a Retrospective, Single-Center Study of Transgender People Undergoing Vaginoplasty.

Introduction: Transgender health care interventions (e.g., gender-affirming surgery) support transgender and gender-diverse people to transition to their gender and are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different institutions spread over several locations). In this exploratory study, we investigated the relationship between centralized and decentralized delivery of transgender health care, client-centeredness, and psychosocial outcomes. Methods: A retrospective analysis of 45 clients undergoing vaginoplasty at one medical center was conducted. Mann-Whitney U tests assessed differences regarding five dimensions of client-centeredness and psychosocial outcomes between the health care delivery groups. To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identified predictors that were actually related to the outcomes. Results: All aspects of client-centered care were scored average or high. Decentralized delivery of care was more client-centered in terms of involvement in care/shared decision-making and empowerment. However, participants from decentralized health care delivery settings scored lower on psychosocial health (p = 0.038-0.005). Conclusions: The factor of (de-)centralized health care delivery appears to have a significant impact on the provision of transgender health care and should be investigated by future research.

How the COVID-19 pandemic affects transgender health care - A cross-sectional online survey in 63 upper-middle-income and high-income countries.

Background: Due to the COVID-19 pandemic, access to medical care is restricted for nearly all non-acute conditions. Due to their status as a vulnerable social group and the inherent need for transition-related treatments, transgender people are assumed to be affected particularly severely by the restrictions caused by the COVID-19 pandemic. Methods: As an ad hoc collaboration between researchers, clinicians and 23 community organizations, we developed a web-based survey in German that was translated into 26 languages. Participants were recruited via community sources, social media channels, and snowball sampling since May 2020. The present sample is based on the data collected until August 9, 2020. We assessed demographical data, health problems, risk factors, COVID-19 data (e.g., contact history), and the influence of the COVID-19 pandemic on access to transgender health care services. To identify factors associated with the experience of restrictions, we conducted multiple logistic regression analysis. Results: 5267 transgender people from 63 upper-middle-income and high-income countries participated in the study. Over 50% of the participants had risk factors for a severe course of a COVID-19 infection and were at a high risk of avoiding COVID-19 treatment due to the fear of mistreatment or discrimination. Access to transgender health care services was restricted for 50% of the participants. Male sex assigned at birth and a lower monthly income were significant predictors for the experience of restrictions to health care. 35.0% reported at least one mental health condition and 3.2% have attempted suicide since the beginning of the COVID-19 pandemic. Discussion: Transgender people suffer under the severity of the pandemic due to the intersections between their status as a vulnerable social group, their high number of medical risk factors, and their need for ongoing medical treatment. The COVID-19 pandemic can potentiate these vulnerabilities, add new challenges for transgender people, and, therefore, can lead to devastating consequences, like severe physical or mental health issues, self-harming behavior, and suicidality.

Centralized and Decentralized Delivery of Transgender Health Care Services: A Systematic Review and a Global Expert Survey in 39 Countries.

Introduction: Transgender health care is delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). However, the health care delivery setting has not gained attention in research so far. Based on a systematic review and a global expert survey, we aim to investigate its role in transgender health care quality. Methods: We performed two studies. In 2019, we systematically reviewed the literature published in databases (Cochrane, MEDLINE, EMBASE, Web of Science) from January 2000 to April 2019. Secondly, we conducted a cross-sectional global expert survey. To complete the evidence on the question of (de-)centralized delivery of transgender health care, we performed a grey literature search for additional information than the systematic review and the expert survey revealed. These analyses were conducted in 2020. Results: Eleven articles met the inclusion criteria of the systematic review. 125 participants from 39 countries took part in the expert survey. With insights from the grey literature search, we found transgender health care in Europe was primarily delivered centralized. In most other countries, both centralized and decentralized delivery structures were present. Comprehensive care with medical standards and individual access to care were central topics associated with the different health care delivery settings. Discussion: The setting in which transgender health care is delivered differs between countries and health systems and could influence different aspects of transgender health care quality. Consequently, it should gain significant attention in clinical practice and future health care research.

Mapping key stakeholders' position towards interdisciplinary transgender healthcare: A stakeholder analysis.

Trans individuals experience an incongruence between their sex characteristics and their gender which might cause significant distress called gender dysphoria. Gender dysphoria is commonly treated using transition-related healthcare services, like sex hormones and surgeries, ideally in interdisciplinary settings. The stakeholder environment of an interdisciplinary transgender healthcare centre (ITHC) is considered key in delivering high-quality healthcare. Therefore, a stakeholder analysis was performed seeking to improve stakeholder relationships and service quality through an evidence-based approach. Quantitative data were collected using a questionnaire administered cross-sectionally, and covering attitude towards the ITHC, influence of and influence on stakeholders, level of knowledge about the ITHC, importance of the ITHC for stakeholders and types of interests. The analysis used primary data, collected July to August 2015. N = 79 key stakeholders were identified and n = 42 (53.2%) participated in the survey. Participants were categorised analytically into four stakeholder groups: trans groups, trans health experts, healthcare system and admin departments of the ITHC. Although participants reported low values (e.g. average values on a 5-point Likert scale; importance: 2.54; influence on the ITHC: 2.43), the attitude of the four stakeholder groups towards the ITHC were positive overall. The attitudes varied, however, depending on the group, for example trans health experts and trans groups reported the highest values for most items. The results demonstrate the importance of systematically analyzing stakeholder positions in order to make appropriate policy decisions, improving stakeholder relationships and assuring long-term high-quality healthcare provision. Subsequently, an action plan was developed, focusing on the two groups with the highest values (trans health experts, trans groups). Selected measures are discussed. If stakeholders are to play their part in providing high-quality, interdisciplinary trans healthcare, they need regular information on the latest developments and recurring feedback of their interests and requirements for the ITHC.

How Gender Identity and Treatment Progress Impact Decision-Making, Psychotherapy and Aftercare Desires of Trans Persons.

The gender identity of trans individuals influences their treatment preferences, and this in turn seems to affect their individual treatment progress. However, there has been no research which-next to the impact of gender identity on treatment desires-has also investigated the influence of treatment progress using a measure which assumes various possible transition pathways of trans persons.Therefore, an online community survey of trans people was conducted in Germany in 2015. Data were collected via an online survey from a non-clinical sample of n = 415 trans individuals (over half assigned female at birth), aged 16-76 (Mean (M) = 38.12). Almost one fifth of participants embraced non-binary or genderqueer (NBGQ) identities. Participants progressed 60.77% (standard deviation (SD) = 35.21) through treatment at point of data collection, as measured by the individual treatment progress score (ITPS). All participants, especially participants assigned male at birth, differed significantly in desire to participate in decision-making processes based on transition progress; individuals without treatment experience had less desire to decide treatment plans. NBGQ participants assigned male at birth in early stages of transition had significantly more desire for psychotherapy during transition than participants of the same identity in later transition stages. All participants, especially binary participants, significantly differed in desire for aftercare based on transition progress; individuals without treatment experience indicated more desire for aftercare. Results indicate health professionals should expect changing treatment desires in trans individuals at various stages of transition, particularly at treatment start, and based on gender identity.

Reviewing the environmental and human health knowledge base of carbon nanotubes.

Carbon nanotubes (CNTs) are considered one of the most promising materials in nanotechnology, with attractive properties for many technologic applications. The different synthesis, purification, and postprocessing methods produce CNTs with different physical characteristics, which can be applied in different fields ranging from composite materials, medical applications, and electronics to energy storage. The widespread projected use of CNTs makes it important to understand their potential harmful effects. In this environmental health review we observed a remarkable range of results of some of the toxicology studies. The comparability should be improved by further standardization and introduction of reference materials. However, at present the findings of this review suggest several key points: a) there are different types of CNTs, and therefore they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. The properties of CNTs suggest a possible accumulation along the food chain and high persistence. In organisms the absorption, distribution, metabolism, excretion, and toxicity of CNTs depend on the inherent physical and chemical characteristics such as CNT functionalization, coating, length, and agglomeration state that are influenced by the external environmental conditions during CNT production, use, and disposal stages. Characterized exposure scenarios could therefore be useful when conducting toxicologic studies. However, CNTs produce a toxic response upon reaching the lungs in sufficient quantity; this reaction is produced in a time-and dose-dependent manner. The identification of possible risks to human health and environment is a prerequisite for a successful introduction of CNTs in future applications.

Needs and concerns of transgender individuals regarding interdisciplinary transgender healthcare: A non-clinical online survey.

This study investigates the needs and concerns transgender (short: trans) individuals have concerning trans healthcare (THC) in interdisciplinary THC centres. Trans individuals' gender does not (fully/constantly) match their sex assigned at birth. To be able to live in their gender role and to prevent or minimise gender dysphoria, they might require a multidisciplinary set of transition related healthcare services. The current shift from the traditionally highly regulated, hierarchical and pathologising approach to THC towards a more patient-centred approach has highlighted the importance of trans patients' satisfaction with treatment processes and results. As the still influential regulations have a negative effect on patient satisfaction, and might also keep trans individuals from seeking transition related treatment, it is crucial to investigate what trans individuals, whether patients or not, need and fear regarding transition related healthcare. Against the backdrop of mixed reactions received from the local trans community regarding the foundation of the Interdisciplinary Transgender Healthcare Centre Hamburg (ITHCCH), Germany, this study seeks to determine what trans individuals need with respect to THC in order to guarantee for high quality service provision at the ITHCCH. To this end, an online questionnaire was developed. The researchers employed a participatory approach to questionnaire development by involving a working group consisting of local trans support group representatives and (THC) specialists (N = 4). The sample consisted of N = 415 trans-identified individuals aged between 16 and 76. Most of them were based in Germany. 85.2% (n = 382) reported experience with transition related healthcare and 72.5% (n = 301) had (additional) treatments planned. Analysis revealed a need for communication and feedback opportunities. Furthermore, during the treatment process, addressing individual needs was considered crucial by participants. They agreed moderately with concerns towards THC centres. 96.5% of participants would like high decision-making power concerning treatment-associated decisions. The results demonstrate the importance of patient-centred THC that takes patients' individual needs and realities into consideration and involves patients in decision-making processes.

Reviewing the environmental and human health knowledge base of carbon nanotubes.

Carbon nanotubes (CNTs) are one of the most promising materials in nanotechnology. The various synthesis, purification and postprocessing methods produce CNTs with diverse physical characteristics, appliable in many fields. Their extensive projected use makes it important to understand their potential harmful effects. Besides showing a notable range of results of some toxicology studies, this review concluded that: a) there are different types of CNTs; thus, they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. Their properties suggest a possible accumulation along the food chain and high persistence. In organisms, CNT absorption, distribution, metabolism, excretion and toxicity depend on the inherent physical and chemical characteristics (e.g., functionalization, coating, length and agglomeration state), influenced by external environmental conditions during CNT production, use, and disposal. Thus, characterized exposure scenarios could be useful in toxicology studies. However, upon reaching the lungs in enough quantity, CNTs produce a toxic response (time and dose-dependent). The risks to human health and environment should be identified for a successful introduction of CNTs in future applications.

Treatment for horseshoe fistulas-in-ano with primary closure of the internal fistula opening: a clinical and manometric study.

INTRODUCTION: We report on a patient cohort with dorsal horseshoe fistulas-in-ano. We sought to answer the question of whether these fistulas can be operatively treated, implementing a sphincter-preserving fistulectomy with primary closure of the internal opening, as is done when treating transsphincteric anal fistulas. Long-term clinical. course is examined here and operative methods are discussed. METHODS: During the time period from 1985 to 2000, 42 patients (29 men, 13 women) with an average age of 44 +/- 11 years were operatively treated for horseshoe fistulas-in-ano originating in cryptoglandular regions. Twenty patients originally had an abscess, which was surgically drained and then a seton was placed in the tract of the fistula. Later, a fistulectomy or curettage of the fistula tract with primary closure of the internal fistula opening was performed in all patients without severing the sphincter muscle. We implemented four different surgical techniques to facilitate this closure: the mucosa-submucosa advancement flap, the rectal wall advancement flap (part or full thickness), the anocutaneous advancement flap, and direct closure without any further mobilization. The follow-up averaged 58 months (1-14 years). RESULTS: Thirty-seven of the 42 fistulas (88 percent) healed. In 31 patients, restitution occurred after the first operation, in 4 patients after the second operation and in 2 patients after the third operation. One patient developed a recurrence after the first operation and died from secondary causes before a second operation was performed. The other four patients were listed as unclear, because the time of observation was less than one year. The total recurrence rate of flap procedures is 23 percent (mucosa-submucosa advancement flap, 25 percent; rectal wall advancement flap, 35 percent; anocutaneous advancement flap, 25 percent; direct closure, 0 percent; not significant). Thirty-four (81 percent) of the 42 patients had previously been operatively treated on an average of three times. Twelve patients developed deficits in continence. Eight patients developed minor deficits, which included incontinence for flatus and problems with staining. Four patients became incontinent for liquid stools. There was a significant decrease in manometric resting pressure of 25 percent (from 123 +/- 40 cm H2O to 91 +/- 29 cm H2O) and in squeeze pressure of 21 percent (from 262 +/- 70 cm H2O to 207 +/- 66 cm H2O). CONCLUSIONS: As in other high anal fistulas, horseshoe-shaped anal fistulas can be operatively treated implementing a fistulectomy combined with any of the above-mentioned forms of closure of the internal fistula opening, with good success rates and acceptable postoperative continence. Sufficient drainage of the retroanal region is of utmost importance. Through these measures, it is possible to avoid severing the sphincter muscle and to prevent an anal canal deformation (keyhole deformity).

Multilocus sequence analysis of Porphyromonas gingivalis indicates frequent recombination.

In this study, the genetic relationship of 19 Porphyromonas gingivalis isolates from patients with periodontitis was investigated by multilocus sequence analysis. Internal 400-600 bp DNA fragments of the 10 chromosomal genes ef-tu, ftsQ, hagB, gpdxJ, pepO, mcmA, dnaK, recA, pga and nah were amplified by PCR and sequenced. No two isolates were identical at all 10 loci. Phylogenetic analyses indicated a panmictic population structure of P. gingivalis. Split decomposition analysis, calculation of homoplasy ratios and analyses of clustered polymorphisms all indicate that recombination plays a major role in creating the genetic heterogeneity of P. gingivalis. A standardized index of association of 0.0898 indicates that the P. gingivalis genes analysed are close to linkage equilibrium.

Reviewing the environmental and human health knowledge base of carbon nanotubes / Revisão sobre a base de conhecimento de saúde ambiental e humana dos nanotubos de carbono

Carbon nanotubes (CNTs) are one of the most promising materials in nanotechnology. The various synthesis, purification and postprocessing methods produce CNTs with diverse physical characteristics, appliable in many fields. Their extensive projected use makes it important to understand their potential harmful effects. Besides showing a notable range of results of some toxicology studies, this review concluded that: a) there are different types of CNTs; thus, they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. Their properties suggest a possible accumulation along the food chain and high persistence. In organisms, CNT absorption, distribution, metabolism, excretion and toxicity depend on the inherent physical and chemical characteristics (e.g., functionalization, coating, length and agglomeration state), influenced by external environmental conditions during CNT production, use, and disposal. Thus, characterized exposure scenarios could be useful in toxicology studies. However, upon reaching the lungs in enough quantity, CNTs produce a toxic response (time and dose-dependent). The risks to human health and environment should be identified for a successful introduction of CNTs in future applications.

Os nanotubos de carbono(CNT)são um dos materiais mais promissores da nanotecnologia. Os métodos de síntese, purificação e pós-processamento produzem CNT com diversas características físicas e uso em várias áreas. A projeção de uso abrangente do CNT urge a compreensão de seus possíveis efeitos nocivos. Essa revisão mostra um leque de resultados de estudos toxicológicos e concluiu que: a) há diferentes tipos de CNT; portanto, não pode ser considerado um grupo uniforme de substâncias; e b) em compartimentos ambientais,o CNT pode ser biodisponível aos organismos. Suas propriedades sugerem possível acúmulo na cadeia alimentar e alta persistência. Em organismos, sua absorção, distribuição, metabolismo, excreção e toxicidade do dependem de características físicas e químicas inerentes (e.g., funcionalização, revestimento, comprimento e estado de aglomeração), influenciadas por condições ambientais externas durante a produção, uso e eliminação de CNT. Portanto, os cenários de exposição caracterizados podem ser úteis em estudos toxicológicos. Contudo, quando chega aos pulmões em quantidade suficiente, o CNT produz uma resposta tóxica (tempo e dose dependente). Os riscos à saúde humana e meio ambiente devem ser identificados para que o CNT possa ser usado com sucesso em futuras aplicações.