Survivorship

Mobility in survivors with chemotherapy-induced peripheral neuropathy and utility of the 6-min walk test Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and often lasting side effect of cancer treatment, with increasing CIPN severity associated with increasing deficits in balance, gait, and mobility. The 6-min walk test (6MWT) is a widely validated and utilized measure of general physical functioning and mobility, although its utility in a CIPN context is unclear. This study aimed to determine the utility of the 6MWT as an assessment of mobility deficits in a CIPN cohort and utilize the 6MWT to compare mobility data from CIPN patients to those of healthy and clinical populations. Methods Cancer survivors exposed to neurotoxic chemotherapies (N = 100; mean 17 ± 13 months post-treatment; mean age 59 ± 13 years) completed a single cross-sectional assessment of patient-reported and objective CIPN, mobility (6MWT), and disability. Results CIPN symptoms were reported in the majority of the cohort (87%). Increasing age, patient-reported and objective CIPN symptoms, and disability were associated with decreasing 6MWT distance (.48 ≤ R ≤ .63; p < .001) in bivariate models. Multiple regression models of 6MWT distance included age, sex, and patient-reported or objective CIPN severity as significant independent correlates (.62 ≤ R ≤ .64; p < .03). 6MWT distances in patients with CIPN symptom severity above the cohort mean were consistent with mean values reported in diabetic neuropathy and clinical populations. Conclusions Increased CIPN symptoms are associated with increased mobility deficits. The 6MWT demonstrates promising utility as a mobility assessment in a CIPN cohort. Implications for Cancer Survivors The impact of the progression of CIPN on mobility deficits in survivors emphasizes the need for effective interventions to treat and prevent CIPN.

Racial and socioeconomic disparities in adherence to preventive health services for ovarian cancer survivors Abstract Purpose To examine ovarian cancer survivors' adherence to evidence-based guidelines for preventive health care. Methods A case-control, retrospective study of Medicare fee-for-service beneficiaries diagnosed with stage I, II, or III epithelial ovarian cancer from 2001 to 2010 using the Surveillance, Epidemiology, and End Results-Medicare database. Survivors were matched 1:1 to non-cancer controls from the 5% Medicare Beneficiary file on age, race, state of residence, and follow-up time. Receipt of flu vaccination, mammography, and bone density tests were examined in accordance with national guidelines. Adherence was assessed starting 1 year after cancer diagnosis, across 2 years of claims. Interaction with the health care system, including outpatient and cancer surveillance visits, was tested as a potential mechanism for receipt of services. Results 2437 survivors met the eligibility criteria (mean age, 75; 90% white). Ovarian cancer survivors were more likely to be adherent to flu vaccination (5 percentage points (pp); < 0.001) and mammography guidelines (10 pp.; < 0.001) compared to non-cancer controls, but no differences were found for bone density test guidelines (− 1 pp.; NS). Black women were less likely to be adherent to flu vaccination and bone density tests compared with white women. Women dually eligible for Medicare and Medicaid were less likely to be adherent compared to those without such support. Adherence was not influenced by measures of outpatient visits. Conclusion Ovarian cancer survivors are receiving preventive services with the same or better adherence than their matched counterparts. Minority and dual-eligible survivors received preventive services at a lower rate than white survivors and those with higher income. The number of outpatient visits was not associated with increased preventive health visits. Implications for Cancer Survivors Ovarian cancer survivors are receiving adequate follow-up care to be adherent to preventive health measures. Efforts to improve care coordination post-treatment may help reduce minority and low SES disparities.

The survivorship experience for patients with metastatic melanoma on immune checkpoint and BRAF-MEK inhibitors Abstract Purpose Immune checkpoint inhibitors (ICI) and BRAF and MEK inhibitors (BMi) have improved survival in metastatic melanoma (MM). However, the experience of long-term responders remains undescribed. This study characterised survivorship issues faced by long-term responders to ICI or BMi. Methods Patients with MM, aged ≥ 18 years old, ≥ 6 months post-ICI or BMi initiation with an objective response or stable disease. A 72-question survey assessed physical and psychological effects, impact on lifestyle, access to information, satisfaction with care, and availability of supports. Results One hundred and five of 120 (88%) patients completed the survey (ICI 69/BMI 36). For the ICI cohort, 39 (57%) were receiving ongoing treatment, 17 ceased due to toxicity and 13 due to a sustained response. For the BMi cohort, 31 (85%) were receiving ongoing treatment, 4 ceased due to toxicity and 1 due to a sustained complete response. At data cut-off on 18 December 2018, median PFS (range) was 2.5 years (1.3–8.5) for ICI and 3.1 years (0.6–7.3) for BMi. Long-term toxicities included dry/itchy skin (ICI 51, 74%/ BMi 25, 69%), arthralgias (ICI 30, 58%/ BMi 23, 64%) and fatigue (ICI 62, 90%/ BMi 33, 92%). Psychological morbidity was common, including anxiety awaiting results (ICI 50, 72%/ BMi 29, 81%), fear of melanoma recurring or progressing (ICI 56, 81%/ BMi 31, 86%) or death (ICI 44, 64%/ BMi 26, 72%). Conclusion MM survivors experience chronic treatment toxicities and frequently report psychological concerns. Implications for Cancer Survivors Survivors may benefit from discussions regarding long-term toxicities and tailored psychological supports.

Correction to: Health care services use among long-term breast cancer survivors: a systematic review The article Health care services use among long-term breast cancer survivors: a systematic review, written by Anna Jansana, Margarita Posso, Inmaculada Guerrero, Alexandra Prados-Torres, Maria Isabel Del Cura, Xavier Castells and Maria Sala, was originally published electronically.

Prescribing fitness apps for people with cancer: a preliminary assessment of content and quality of commercially available apps Abstract Purpose The benefits of physical activity for cancer survivors are increasingly recognised and smartphone applications are available to assist them to become more physically active. Cancer clinicians, however, lack confidence about which physical activity apps to recommend as evidence on their quality and content is limited. Therefore, we reviewed freely available commercial physical activity/fitness apps to systematically assess their behavioural change content and quality of their design. Methods Systematic searches of the app stores for Apple and Android operating systems were conducted and apps were screened to identify free apps appropriate for cancer survivors. Quality was assessed using the Mobile App Rating Scale (MARS) and behavioural content was evaluated using the Behavioural Change Techniques Taxonomy (BCTT). Results Of 341 apps identified, 67 were judged appropriate for cancer survivors and 46% combined aerobic and strength/stretching content. The overall number of behavioural change techniques (BCT) included was 3.96 (SD = 2.09), with the most frequent being 'feedback on behaviour' and 'goal setting behaviour'. The mean scores for objective and subjective quality were 4.11 (SD = 0.59) and 3.07 (SD = 0.91) respectively (range 0 to 5). Finally, a modest positive correlation was found between the number of BCT and the quality of engagement, awareness and knowledge as assessed by the MARS. Conclusion Only a fifth of retrieved physical activity apps contained potentially suitable content for people affected by cancer. Overall, most apps we reviewed appeared to perform well in terms of their objective quality, but less well at promoting knowledge and awareness or help seeking related to physical activity. Implications for Cancer Survivors Many physical activity apps are available but the combined use of MARS and BCTT suggests that not all of them are suitable to the needs is a promising and feasible approach for assessing the applicability, usability and content of physical activity of apps employed by cancer survivors and this study is a first step toward developing a guide.

Contraceptive utilization and counseling among breast cancer survivors Abstract Purpose To explore contraceptive counseling and utilization among breast cancer survivors. Methods We enrolled reproductive-aged women with a history of breast cancer for a cross-sectional study. Participants were recruited via the Athena Breast Health Network and via the Young Survival Coalition's social media postings. Descriptive statistics were calculated to understand utilization of and feelings about contraceptive methods before, during, and after breast cancer treatment. Results Data presented here are from an online survey of 150 breast cancer survivors who completed the survey. Seventy-one percent (n = 105) of respondents reported being sexually active and not pregnant during their primary cancer treatment (surgery, chemotherapy, and/or radiation). Of these, 90% (n = 94) reported using any form of contraceptive, and the most common method was condoms (n = 55, 52%). Respondents reported that safety concerns had the biggest influence on their contraception method choice. Sixty-one percent (n = 92) reported receiving contraceptive counseling by their oncologist either before or after treatment; however, 49% (n = 45) of those did not receive a specific recommendation for a contraceptive method. Of respondents who reported receiving contraceptive counseling from their gynecologist, 44% (n = 35) reported that their gynecologist specifically recommended a copper intrauterine device (IUD). The majority of respondents (n = 76, 52%) wanted their oncologist to discuss contraceptive options with them and preferred to receive this counseling at the time of diagnosis (n = 81, 57%). Conclusions Breast cancer survivors in this study remained sexually active across the cancer care continuum and predominantly used condoms as their contraceptive method during treatment. Breast cancer patients would prefer contraceptive counseling from their oncologist at the time of their cancer diagnosis. Implication for Cancer Survivors Education efforts in the future should focus on initiatives to improve comprehensive contraceptive counseling at the time of diagnosis by an oncologist.

Impact of lymphoma survivorship clinic visit on patient-centered outcomes Abstract Purpose Cancer survivors may experience physical, social, and emotional effects of cancer and its treatments. National Comprehensive Cancer Network (NCCN) guidelines recommend the development of a survivorship care plan (SCP) for cancer patients following completion of treatment with curative intent. Our institution developed a lymphoma survivorship clinic (SC) to assess patient needs, provide education, and create and deliver SCPs. This study analyzed the impact of a SC visit on patient-centered outcomes. Methods Surveys were sent to lymphoma patients at Mayo Clinic Rochester within 4 weeks of their post-treatment visit to the SC that queried patient-reported outcomes, including experience of care, quality of life (QOL), and distress. We compared survey responses between those who attended the SC and those who were eligible but did not attend. Results From November 2013 to May 2015, 236 lymphoma patients were surveyed, 96 of whom had a SC visit and 140 of who were eligible but did not attend. Those who attended the SC were more likely to "definitely" recall discussion on improving health, preventing illness, and making changes in habits/lifestyle, diet, and exercise. There were no differences in QOL or distress. Adjusted analyses revealed that SC attendance was associated with better self-reported overall health among younger patients and better physical well-being in Hodgkin lymphoma patients compared to those with other subtypes of lymphoma. Conclusions Participation in the lymphoma SC improved patient education on survivorship issues, particularly health behaviors. There may be a particular benefit in younger patients. However, there were no differences in QOL or distress. Further study is needed to determine if improved survivorship education and SCP delivery leads to long-term health benefits in cancer survivors. Implications for Cancer Survivors Our study evaluates the clinical impact of a SC in patients treated for lymphoma. We demonstrate that a SC visit improves patient education regarding health behaviors.

Adherence to multiple health behaviours in cancer survivors: a systematic review and meta-analysis Abstract Purpose Multiple health behaviours (not smoking, minimal alcohol consumption, and maintaining a healthy weight by having a healthy diet and regular physical activity) improve quality of life and longevity of cancer survivors. Despite international guidelines, there are no existing reviews that synthesise cancer survivors' adherence to healthy lifestyle recommendations. Method Five databases (Embase, MEDLINE, PsycINFO, Web of Science, and Google Scholar) were searched for relevant articles published from 2007 until January 2018. Studies reporting adult cancer survivors' adherence to at least two lifestyle behaviours (body mass index, physical activity, smoking, fruit and vegetable intake, fiber intake, red meat intake, caloric intake, sodium intake, and alcohol consumption) based on the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations were included in the review. The pooled prevalence of adherence to single and multiple behaviours was calculated using a random-effects model. Subgroup analysis (mean years of survival and publication year) was undertaken. Results A total of 3322 articles were identified. Of these, 51 studies matched the inclusion criteria, presenting data from 2,620,586 adult cancer survivors. Adherence to single behaviours, which was estimated from studies that assessed at least two health behaviours, was highest for not smoking (PE 87%; 95% CI, 85%, 88%) and low or no alcohol intake (PE 83%; 95% CI, 81%, 86%), and lowest for fiber intake (PE 31%; 95% CI, 21%, 40%). Adherence to multiple healthy behaviours (13 studies), ranged from 7 to 40% (pooled estimate (PE) 23%; 95% CI, 17%, 30%). Recent survivors (< 5-year survival time) had relatively better adherence to multiple behaviours (PE 31%; 95% CI, 27%, 35%) than long-term (> 5 years) survivors (PE 25%; 95% CI, 14%, 36%). Adherence to multiple behaviours improved over time since 2007. Conclusion Adherence to physical activity, dietary, and multiple lifestyle behaviours recommendations was low amongst cancer survivors. Recent cancer survivors were relatively more adherent to WCRF/AICR recommendations compared to long-term survivors. Implications for Cancer Survivors Health promotion programs help support healthy lifestyle behaviours of cancer survivors. PROSPERO registration number: CRD42018091663

Breast cancer survivors reduce accelerometer-measured sedentary time in an exercise intervention Abstract Purpose Cancer survivors are highly sedentary and have low physical activity. How physical activity interventions impact sedentary behavior remains unclear. This secondary analysis examined changes in sedentary behavior among breast cancer survivors participating in a physical activity intervention that significantly increased moderate-to-vigorous physical activity (MVPA). Methods Insufficiently active breast cancer survivors were randomized to a 12-week physical activity intervention (exercise arm) or control arm. The intervention focused solely on increasing MVPA with no content targeting sedentary behavior. Total sedentary behavior, light physical activity (LPA), and MVPA were measured at baseline and 12 weeks (ActiGraph GT3X+ accelerometer). Separate linear mixed-effects models tested intervention effects on sedentary behavior, intervention effects on LPA, the relationship between change in MVPA and change in sedentary behavior, and potential moderators of intervention effects on sedentary behavior. Results The exercise arm had significantly greater reductions in sedentary behavior than the control arm (mean − 24.9 min/day (SD = 5.9) vs. − 4.8 min/day (SD = 5.9), b = − 20.1 (SE = 8.4), p = 0.02). Larger increases in MVPA were associated with larger decreases in sedentary behavior (b = − 1.9 (SE = 0.21), p < 0.001). Women farther out from surgery had significantly greater reductions in sedentary behavior than women closer to surgery (b = − 0.91 (SE = 0.5), p = 0.07). There was no significant group difference in change in LPA from baseline to 12 weeks (b = 5.64 (SE = 7.69), p = 0.48). Conclusions Breast cancer survivors in a physical activity intervention reduced total sedentary time in addition to increasing MVPA. Implications for Cancer Survivors Both increasing physical activity and reducing sedentary behavior are needed to promote optimal health in cancer survivors. These results show that MVPA and sedentary behavior could be successfully targeted together, particularly among longer-term cancer survivors. Clinical trial registration This study is registered at www.ClinicalTrials.gov (NCT 02332876).

The social and economic toll of cancer survivorship: a complex web of financial sacrifice Abstract Purpose To assess the financial outcomes and associated social and economic effects on cancer survivors and their families. Methods We assessed the responses of 1656 cancer survivors to a survey with both closed- and open-ended questions about cancer-related financial sacrifices they and their family experienced and evaluated differences in financial sacrifice by reported levels of cancer-related debt. Results The most commonly reported financial sacrifices included cutbacks on household budgets, challenges with health care insurance and costs, career/self-advancement constraints, reduction/depletion of assets, and inability to pay bills. Survivors who incurred $10,000 or more in debt were significantly more likely to report social and economic impacts, including housing concerns and strained relationships. Conclusions Our analysis demonstrates both the frequency with which cancer survivors and families must make financial sacrifices as a result of their cancer, and the variety of forms that this sacrifice can take, even for individuals who have health insurance. The many types of financial hardship create challenges that are unique to each survivor and family. Implications for Cancer Survivors Interventions that allow for personalized assistance with the specific financial and social needs of cancer survivors and their families have the potential to address a critical aspect of the long-term wellbeing of this important population.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Gerontology

Do Income Supplemental Programs for Older Adults' Help Reduce Primary Caregiver Burden? Evidence from Mexico Abstract In countries such as Mexico without formal public long-term care policies, informal care becomes the main source of support for older adults. Alternative social programs, such as supplemental income programs, for older adults could alleviate caregiver burden, especially if supplemental income were to be used for paid care or to compensate non-paid family caregivers. This work is the first to analyze the effects of a supplemental income program for older adults on primary caregiver burden. To identify how such a program might affect caregiver burden, we analyze rich panel data on 433 adults 70 years and older in two communities, one receiving a supplemental income program and the other not, in Yucatan, Mexico. Data were collected in 2008 and 2009 among treatment and control groups before and 6 months after program introduction. We employ a difference-in-differences approach. In our sample, most care is provided by non-paid female caregivers. We find that individuals in both the treatment and control groups received fewer hours of care over time. The decrease was lower for older adults who received the supplemental income, but the difference with those who did not was not statistically significant. We also observe few changes on caregiving burden; even after program introduction, more than 98% of caregivers remained unpaid and the same primary caregiver remained. Altogether, our work suggests supplemental income programs have negligible effects on caregiving, making evident the urgent need for other strategies to support non-paid caregivers who bear most of the burden for old-age care in Mexico.

Risk and Resiliency in the Relationship Between Widowhood and Depressive Symptoms Among Older Mexican Americans Abstract This study examined the association between widowhood and depressive symptoms and the extent to which the association is contingent upon risk and resiliency, including immigration status, functional limitations, financial strains, and intergenerational support, among older Mexican Americans. The sample included 344 parent-child pairs reported by 83 respondents. Clustered regression analysis showed that widowhood elevated risks for depressive symptoms. We found that having some functional limitations, having more children and living in the same city with children exacerbated the adverse effects of widowhood on depressive symptoms. We also found that living in the same city with children increased the detrimental effects of widowhood on the depressive symptoms in men, whereas we did not find this pattern in women. The findings highlight the heterogeneity within the widowed Mexican American older adults. Implications for future research and practice are discussed.

Rural Native and European American Custodial Grandparents: Stressors, Resources, and Resilience Abstract Native American grandparents by tradition are expected to play a role in rearing grandchildren. However, in many Native grandfamilies, grandparents are rearing grandchildren not by choice or tradition, but as the result of family crises that necessitated grandparent intervention. European American grandparents have likewise been called to rear their grandchildren when their adult children are unable or unwilling to perform parental duties. Less is known about these custodial grandparents' resilience pathways, particularly among rural grandfamilies. Guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation, this study examined the relationships between stressors, resources, and resilience among rural Native and European American custodial grandparents. Correlates of resilience were economic stress and stress management. Significant interactions were found between economic stress and government assistance and economic stress and stress management, indicating complex resilience pathways. Implications of study findings for research and intervention are discussed.

"I Go Upstairs and Eat in Front of the Television:" the Cooking and Eating Behaviors of Mexican Older Women Living Alone Abstract The increasing tendency of older people living alone may pose a number of challenges including factors related to food insecurity, such as functional impairment, social isolation, and financial vulnerability. The purpose of this study was to explain the cooking and eating behaviors of Mexican older women living alone using a life course perspective. A qualitative research methodology was chosen and deductive thematic analysis was used to examine accounts given by 14 older women through one-on-one interviews. Findings showed that age-related transitions, role changes, and the social context in which older women are embedded have changed their cooking and eating behaviors. Participants mentioned the need to accept and adapt to changes in later life; however, the loss of commensality, cooking for one, economic constraints, a decline in health, and the disruption of family roles and rituals were identified as the negative aspects affecting the cooking and eating behaviors of older women.

Cognitive Advantages in Adult Turkish Bilingual Immigrants – a Question of the Chicken or the Egg Abstract A number of studies suggest both cognitive disadvantages and advantages of bilingualism. In the current study, it is attempted to provide an account of the cognitive advantages associated with bilingualism in a Turkish immigrant population in Denmark.The total sample consisted of 71 middle-aged and older adults born and raised in Turkey who had migrated to Denmark in their teenage years or later. All participants were assessed with a neuropsychological test battery and degree of Turkish-Danish bilingualism was estimated via rater assessment according to a three-point scale. Associations between bilingualism and cognitive function were established for five cognitive domains: executive function, memory, language, visuospatial function and speed. Analysis of covariance was used to estimate the independent association between bilingualism and cognitive function for each cognitive domain. Covariates included education, gender, ethnicity, and proportion of life lived in Denmark. In unadjusted analyses, greater degree of bilingualism was associated with better executive functioning (p < .001), visuospatial functioning (p = .002) and speed (p < .001). However, in analyses adjusted for covariates only executive functioning (p = .01) and task switching ability (p = .01) remained significant, while a trend for better memory function was found in those with a high degree of bilingualism (p = .07).The current study indicates that bilingual Turkish immigrants have better executive functioning and episodic memory compared to Turkish immigrant monolinguals. Whether this is due to the effects of bilingualism or reflects inherent cognitive abilities in those able to acquire bilingualism in later life remains to be resolved.

Early Hour, Golden Hour: an Exploration of Slovenian Older People's Meaningful Occupations Abstract People are occupational beings and enabling older people to engage in meaningful occupations contributes to their health and well-being. Experiences of engagement and meaning in an occupation may differ in different socio-cultural contexts. The aim of this study was to explore Slovenian older people's individual experiences of engagement in occupation, with a particular emphasis on their meaningful occupations. The study employed a phenomenological research approach. Semi-structured interviews were conducted with ten Slovenian older adults, living independently in their home environment. Interpretative Phenomenological Analysis was used to approach and analyze the data. The findings highlighted that meaningful occupations and daily rituals represented an important part of the participants' identities. The meanings they attached to their occupations were informed by Slovenian socio-cultural, historical and physical context. A range of people and places were identified as significant in generating and maintaining these meanings. Participants gave particular significance to the role of productive, health-promoting and family-related occupations. The study contributes new occupational science knowledge and the findings support the case for increased recognition of the importance of meaningful occupation for older people.

Planning Ahead for End-of-Life Healthcare among Iranian-American Older Adults: Attitudes and Communication of Healthcare Wishes Abstract The purpose of this study was to examine relationships between attitudes toward planning for end-of-life (EOL) care and social supports, spirituality, distrust of the US healthcare system, and acculturation; and to investigate a relationship between attitudes and communication of EOL wishes in Iranian-American older adults. A descriptive, cross-sectional study was used. Older adults (N = 135) were surveyed using Qualtrics online software. The participants were new immigrants to the U.S., highly educated, and insured with a generally positive self-reported health status. Of this sample, 47.4% reported that they communicated their EOL wishes orally or through written documentation. Favorable attitudes toward planning were associated with acculturation and healthcare system distrust, and, inversely, were negatively associated with spirituality. No significant association was found between attitudes and social support. Favorable attitudes predicted participants' communication of wishes. The findings can inform the provision of effective interventions to enhance culturally competent EOL care.

Overcoming a Bad Day: a Qualitative Look into the Dementia Caregiving Experiences of Mexican-Origin Women in East Los Angeles Abstract The number of Latinos with Alzheimer's disease (AD) is projected to more than double by 2030. Yet, the current literature is lagging on Alzheimer's caregiving among Latinos. This study explores how Mexican origin women experience dementia caregiving, and the coping strategies they use to manage their caregiving situations. Nine women were identified as caregivers of a family member with AD or dementia from a larger study on caregiving. Interviews with them were collected and subsequently analyzed using a modified grounded theory approach to reduce the data to identify thematic content. All but one participant described caregiving as "tiring," "wearing," or "hard." They reported suffering from stress, insomnia, nervousness, migraines, and/or depression because of their caregiving experiences. Participants engaged in various coping strategies to help combat the perceived negative consequences of their caregiving experiences. The most commonly reported strategies were various forms of distraction, and meditation or prayer. The Mexican origin women in this study experience faced two types of interpersonal challenges related to dementia caregiving: changes in the care receiver's personality and behaviors, and physical care needs. They engaged in various coping to strategies to address the difficulties of their situation. This study provides formative research for identifying research questions and topics of examination in the future.

Attitudes Towards and Use of Information and Communication Technologies (ICTs) Among Older Adults in Italy and Sweden: the Influence of Cultural Context, Socio-Demographic Factors, and Time Perspective Abstract This study examined determinants of attitudes towards and use of information and communication technologies (ICTs) in older adults, including variations in cultural context, socio-demographic factors (age, education, and gender) and the individual's time perspective. Towards this end, 638 older adults in Italy (n = 262, M = 71.7 years) and Sweden (n = 376, M = 69.9 years) completed the Swedish Time Perspective Inventory (S-ZTPI), the Attitude toward Technologies Questionnaire (ATTQ), and questions regarding use of specific digital technologies (e.g. Internet, Skype, Facebook); data were collected in 2013–2014. The results showed more positive attitudes toward ICTs in Swedish compared with Italian elderly as well as more frequent use of technologies. Regardless of nationality, younger age and higher levels of educational attainment was positively associated with attitudes towards ICTs. Male gender was associated with higher ATTQ scores in the Italian, but not in the Swedish, sample. Time perspective accounted for significant variance beyond the foregoing variables. S-ZTPI Past Negative, Future Negative and Present Fatalistic in particular, were (negatively) related to ATTQ scores, with a similar pattern for ICT use. Future Positive and Present Hedonistic were positively associated with ATTQ scores, across the samples. In conclusion, between-person differences in time perspective organization are an important factor to account for variability in attitudes towards and use of ICTs in old age, and appears to exert an influence over and beyond other significant predictors, such as cultural context, age/cohort membership, and educational level.

Language and Culture in the Caregiving of People with Dementia in Care Homes - What Are the Implications for Well-Being? A Scoping Review with a Welsh Perspective Abstract The loss of language skills is one of the most challenging aspects of living with dementia. This is particularly true for bilingual individuals, who have difficulty in maintaining fluency in more than one language. Language and culture overlap greatly, with potential implications for the well-being of people with dementia (PWD) being cared for in their 'second' language or culture. Our aim was to review the available relevant literature, together with an examination of the potential effects of linguistic incongruity on healthcare in general for Welsh speakers in Wales. A literature search yielded 50 articles, which were analysed using the scoping review methodological framework. We found that the presence of cultural and linguistic congruity was beneficial for PWD living in care homes, and that their absence was detrimental. The absence of linguistic congruity is a strong predictor for decreased well-being in people in such settings, due to communication barriers between residents and carers, which result mainly from the loss of PWD's second language skills. Such barriers may lead to inappropriate care, e.g. being unable to obtain help to self-care, as well as social isolation. This review suggests that strategies need to be developed across the world to accommodate bilingual individuals requiring a care home for their dementia needs. There is a particular dearth of research regarding the influence of bilingualism on the experience of dementia care in those areas of the UK where the indigenous population are most likely to be bilingual (i.e. parts of Wales).

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Der Hautarzt

Fallstrick kryothermische Dermatitis artefacta Zusammenfassung Wir präsentieren 4 klinisch-histologisch korrelierte Fälle junger Patienten mit kryothermischer Dermatitis artefacta, die initial als primär bullöse Dermatosen oder Arzneimittelreaktionen fehldiagnostiziert wurden. Die kryothermische Dermatitis artefacta weist Ähnlichkeiten mit authentischen Dermatosen wie der linearen Ig(Immunglobulin)A-Dermatose, Herpes-Virus-Infektion, dem bullösen Pemphigoid oder einer fixen Arzneimittelreaktion auf. Sie sollte als Differenzialdiagnose bei ungewöhnlichen Verläufen wiederkehrender Blasen bei adoleszenten und jungen erwachsenen Patienten mit in Betracht gezogen werden. Wir fassen die klinischen und histologischen Merkmale zusammen, die für die korrekte Diagnosestellung und damit ursächliche Behandlung der Patienten hilfreich sind.

Rezepturvorschläge zu Mometasonfuroat-Kombinationen

Einfluss von Ernährung, autoimmunen Volkskrankheiten und Rauchen auf die Erkrankungshäufigkeit von Fußmykosen Zusammenfassung Hintergrund Fußmykosen einschließlich Onychomykosen sind weltweit verbreitete Infektionserkrankungen. Zur Abklärung möglicher präventiv nutzbarer Einflussfaktoren sollte erstmalig im Rahmen einer regional landesweiten flächendeckenden Erhebung anhand zufällig ausgewählter Einwohner in Mecklenburg‐Vorpommern der Einfluss bestimmter Ernährungsgewohnheiten, häufiger autoimmuner Komorbiditäten und Rauchen auf die Prävalenz von Fußmykosen untersucht werden. Ziele Es erfolgte die Ermittlung potenzieller neuer Einflussfaktoren der Mykoseentstehung, um ggf. präventive Maßnahmen ableiten zu können. Methodik Im Rahmen der Study of Health in Pomerania (SHIP) in Mecklenburg‐Vorpommern wurden insgesamt 2523 Probanden auf das Vorliegen von Mykosen am Körper untersucht und mykologisch beprobt. Mittels Fragebogen wurden die Komorbiditäten Leiden unter Allergie, Heuschnupfen, Neurodermitis und Psoriasis erfragt, außerdem Ernährungsgewohnheiten sowie Rauchverhalten. Ergebnisse Bei 8 % der 2504 untersuchten Probanden wurde eine Mykose am Körper, bei 6,5 % eine Onychomykose, bei 3,7 % eine Tinea pedis und bei 0,2 % Tinea corporis diagnostiziert. Tinea pedis zeigte eine signifikante Assoziation mit Psoriasis, Heuschnupfen und atopischer Dermatitis sowie mit häufigem Verzehr von gekochten Kartoffeln, Haferflocken, Müsli, Cornflakes, Teigwaren und Reis. Die Onychomykose zeigte eine positive Assoziation mit dem gehäuften Verzehr von gekochten Kartoffeln. Zigarettenkonsum war im Trend protektiv für das Auftreten kulturpositiver Fußmykosen, dabei signifikant protektiv gegenüber dem Nachweis von Dermatophyten allgemein und signifikant gegenüber Trichophyton (T.) rubrum und T. mentagrophytes complex. Schlussfolgerungen Die Autoimmunkrankheiten Psoriasis und atopische Dermatitis und Rhinitis allergica scheinen Fußpilzerkrankungen zu begünstigen. Bei rezidivierenden Fußmykosen sollte eine kohlenhydratreiche Ernährung hinterfragt werden. Nikotingenuss scheint die Haut vor Pilzbefall und möglicherweise auch vor klinischer Manifestation zu schützen.

Schnitzler syndrome Abstract Schnitzler syndrome is a very rare acquired systemic disease with many similarities to hereditary autoinflammatory syndromes. The main characteristics are generalized exanthema and IgM monoclonal gammopathy. Other clinical features include fever, muscle, bone, and/or joint pain, and lymphadenopathy. About 15–20% of patients with Schnitzler syndrome develop lymphoproliferative diseases and, in rare cases, amyloid A (AA) amyloidosis can occur if the disease is not treated. Activation of the innate immune system, especially interleukin (IL)-1β, is central to the pathogenesis of disease. Consequently, complete control of disease symptoms can be achieved in 80% of patients by treatment with the IL-1 receptor antagonist anakinra.

Genomnachweis von Dermatophyten Zusammenfassung Für die Diagnostik bei Verdacht auf Dermatophytosen sind neben der Kulturdiagnostik seit einiger Zeit auch molekulargenetische Verfahren verfügbar. Seit März 2016 bietet INSTAND e. V. in Zusammenarbeit mit dem Nationalen Konsiliarlabor für Dermatophyten 2‑mal jährlich einen Ringversuch für den Genomnachweis von Dermatophyten an. Mehr als die Hälfte der Teilnehmer dieses Ringversuchs verwenden für die Analyse der Ringversuchsproben kommerzielle Kits. Proben, die Trichophyton rubrum oder keinen Dermatophyten enthielten, wurden von allen Kits mit hoher Sicherheit korrekt bestimmt. Bei der Speziesdiagnostik über Trichophyton rubrum hinaus gibt es große Unterschiede zwischen den einzelnen Kits. Diese werden hier anhand von klinischen Studien und den Ergebnissen aus dem Ringversuch näher beleuchtet.

Bedeutung des adäquaten Drucks in der Kompressionstherapie Zusammenfassung Hintergrund Der Druck, der von einem Kompressionsmittel auf ein Körperteil ausgeübt wird, entspricht der Dosierung der Kompressionstherapie. Daher sollten die Druckverläufe unter Kompressionsmaterialien in unterschiedlichen klinischen Situationen untersucht werden. Material und Methoden Es wurden Druckmessungen unter verschiedenen Kompressionsmaterialien im Liegen, im Stehen und im Gehen im Rahmen von Schulungen, im Selbstversuch sowie bei Patienten mit Ulcus cruris venosum durchgeführt. Ergebnisse In Abhängigkeit von dem verwendeten Material, der Festigkeit beim Anlegen, der lokalen Konfiguration (Körperhaltung) und dem Zeitabstand zur Anlage variiert der Druck beträchtlich. Unter jeder Kompressionstherapie tritt ein Druckverlust auf, besonders unter unelastischem Kurzzugmaterial; dies ist vorwiegend durch Bewegung und Ödemreduktion bedingt. Dieser Druckverlust ist ausschlaggebend für den Zeitpunkt des Verbandwechsels und ein Grund für die gute Verträglichkeit von hohen Druckwerten bei mobilen Patienten. Schlussfolgerung Niedrige Drücke eignen sich v. a. zur Ödemreduktion. Hämodynamische Effekte benötigen höhere Drücke (60–80 mmHg). Hierfür wird unelastisches Material bevorzugt, das niedrigere Drücke im Liegen erlaubt (40–60 mmHg). Da Kompressionsverbände von vielen Anwendern zu locker angelegt werden, sind Druckindikatoren auf Binden oder adaptive Bandagen mit Schablonen hilfreich, um das Material mit korrektem Druck anzuwenden. Als Konsequenz dieser Erkenntnisse ist zu fordern, dass zumindest in Studien zum Vergleich verschiedener Kompressionsmittel zukünftig Druckmessungen durchgeführt werden sollten, wobei der Messpunkt und die Körperhaltung anzugeben sind.

Follikuläre Hyperkeratosen bei Zöliakie

Erratum zu: 31/w mit livid-erythematösen Papeln und Knoten. Vorbereitung auf die Facharztprüfung: Folge 6 Erratum zu: Der Hautarzt 2018 https://doi.org/10.1007/s00105-018-4240-4 Sehr geehrte Leserin, sehr geehrter Leser, in Tab. 1 des oben genannten Beitrags wurde der sog. kutane inflammatorische Pseudotumor leider falsch zugeordnet. Er gehört zu den B‑Zell-Pseudolymphomen. Die richtige Tabellenversion …

Primärprävention im Rahmen des Hautkrebsscreenings Zusammenfassung Hintergrund Das Programm zur Früherkennung von Hautkrebs in Deutschland dient der frühzeitigen Identifizierung von Hauttumoren mit dem Ziel der risikoärmeren Entfernung und der Vermeidung einer Progression. Ziel der Arbeit Ziel der Studie ist es zu untersuchen, inwieweit im Zuge der Früherkennungsuntersuchung auf Hautkrebs (HKS) auch primärpräventives Wissen vermittelt wird. Methoden Diese Fragestellung wurde aus Sicht von Screeningteilnehmern und Dermatologen untersucht. Der Anteil an entsprechend informierten Personen unter den Gescreenten wurde anhand einer Befragung einer repräsentativen Stichprobe der deutschen Standardbevölkerung von n = 1004 Personen ermittelt. Die Vermittlung von Informationen zu primärpräventivem Verhalten wurde anhand einer Befragung dermatologischer Praxen (n = 444) erfasst. Beide Erhebungen wurden deskriptiv ausgewertet. Ergebnisse In der Allgemeinbevölkerung gab unter denjenigen Personen, die ein HKS bei sich durchführen ließen (n = 397), der Großteil (74 %) an, dass im Zuge des Screenings Informationen über den Schutz vor UV-Strahlen vermittelt wurden. Unter den Dermatologen, die das HKS anbieten (n = 424), gaben 70 % an, alle HKS-Teilnehmer über Maßnahmen zur Vorbeugung von Hautkrebs persönlich zu informieren, 46 % gaben stets oder überwiegend schriftliches Material im Anschluss an das HKS aus. Diskussion Dem HKS kommt neben der sekundärpräventiven auch eine wichtige primärpräventive Funktion zu, wobei Verbesserungspotenzial besteht, da ca. ein Viertel der HKS-Teilnehmer keine Informationen zu präventivem Verhalten vom untersuchenden Arzt erhält. Die Beantwortung der Frage, in welchem Umfang diese Informationen von den HKS-Teilnehmern tatsächlich umgesetzt werden, bedarf einer Längsschnittstudie.

Diffuse plane Xanthome bei Mycosis fungoides Zusammenfassung Kutane Xanthome werden bei Patienten mit Störungen im Lipidmetabolismus, chronisch inflammatorischen oder malignen Erkrankungen beobachtet. Insbesondere bei myeloproliferativen Erkrankungen können dystrophe Xanthome auftreten. Wir berichten über einen normolipämischen Patienten mit xanthomatisierten Hautveränderungen im Rahmen einer Mycosis fungoides (MF), dem häufigsten kutanen T‑Zell Lymphom. Neben illustrativen klinischen und histopathologischen Bildern wird eine Literaturübersicht bezüglich dystropher Xanthome bei Mycosis fungoides präsentiert.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

HEC Forum is an international, peer-reviewed publication featuring original contributions of interest to practicing physicians, nurses, social workers, risk managers, attorneys, ethicists, and other HEC committee members. Contributions from all pertinent sources are included, written in a style written appealing to HEC members and lay readers. HEC Forum publishes essays and research papers, and includes such sections as Essays on Substantive Bioethical/Health Law Issues; Analyses of Procedural and Operational Committee Issues; Document Exchange; Special Articles; International Perspectives; Mt./St. Anonymous: Cases and Institutional Policies; Point/Counterpoint Argumentation; Case Reviews, Analyses, and Resolutions; Chairperson's Section; `Tough Spot'; Critical Annotations; Health Law Alert; Network News and Letters to the Editors. HEC Forum is an official partner journal of the American Society for Humanities + Bioethics: http://www.asbh.org/

The Clinical Ethics Consultant: What Role is There for Religious Beliefs? Abstract Religions often operate as comprehensive worldviews, attempting to answer the deepest existential questions that human beings can ask: Who am I? Where do I come from? Where am I going after I die? How should I live? Often ethical systems are embedded and justified within these broader narratives. Inevitably, the clinical ethics consultant will encounter and engage with religiously based ethical systems. In this issue, the authors reflect seriously and deeply on the implications of such engagement.

The Appropriate Role of a Clinical Ethics Consultant's Religious Worldview in Consultative Work: Nearly None Abstract Ethical reasoning is an integral part of the work of a clinical ethics consultant (CEC). Ethical reasoning has a close relationship with an individual's beliefs and values, which, for religious adherents, are likely to be tightly connected with their spiritual perspectives. As a result, for individuals who identify with a religious tradition, the process of thinking through ethical questions is likely to be influenced by their religious worldview. The connection between ethical reasoning and one's spiritual perspective raises questions about the role that CECs' personal religious worldviews should play in their professional lives and their consultative work. This paper offers numerous arguments critiquing the inclusion of a consultant's own spiritual perspective in her work and has identified only limited circumstances under which such inclusion might be permissible. In particular, these arguments lead to the conclusion that a CEC's personal beliefs should never influence her ethical analysis or development of a recommendation. Further, religious appeals should not be used in communication during decision-making conversations other than to describe the patient or surrogate's stated perspective. There may be limited cases in which a CEC may share her spiritual worldview with a patient with the intent of building a collaborative relationship, but such situations should be approached with extreme caution.

Moral Conflicts and Religious Convictions: What Role for Clinical Ethics Consultants? Abstract Moral conflicts over medical treatment that are the result of differences in fundamental moral commitments of the stakeholders, including religiously grounded commitments, can present difficult challenges for clinical ethics consultants. This article begins with a case example that poses such a conflict, then examines how consultants might use different approaches to clinical ethics consultation in an effort to facilitate the resolution of conflicts of this kind. Among the approaches considered are the authoritarian approach, the pure consensus approach, and the ethics facilitation approach described in the Core Competencies for Healthcare Ethics Consultationreport of the American Society for Bioethics and Humanities, as well as a patient advocate approach, a clinician advocate approach, and an institutional advocate approach. The article identifies clear limitations to each of these approaches. An analysis of the introductory case illustrates those limitations, and the article concludes that deep-seated conflicts of this kind may reveal inescapable limits of current approaches to clinical ethics consultation.

Religion, Authenticity, and Clinical Ethics Consultation Abstract A clinical ethics consultant (CEC) may, at times, be called upon to make independent substantive moral judgments and then offer justifications for those judgments. A CEC does not act unprofessionally by utilizing background beliefs that are religious in nature to justify those judgments. It is important, however, for a CEC to make such judgments authentically and, when asked, to offer up one's reasons for why one believes the judgment is true in a transparent fashion.

When Religion and Medicine Clash: Non-beneficial Treatments and Hope for a Miracle Abstract Patient and family demands for the initiation or continuation of life-sustaining medically non-beneficial treatments continues to be a major issue. This is especially relevant in intensive care units, but is also a challenge in other settings, most notably with cardiopulmonary resuscitation. Differences of opinion between physicians and patients/families about what are appropriate interventions in specific clinical situations are often fraught with highly strained emotions, and perhaps none more so when the family bases their desires on religious belief. In this essay, I discuss non-beneficial treatments in light of these sorts of disputes, when there is a clash between the nominally secular world of fact- and evidence-based medicine and the faith-based world of hope for a miraculous cure. I ask the question whether religious belief can justify providing treatment that has either no or a vanishly small chance of restoring meaningful function. I conclude that non-beneficial therapy by its very definition cannot be helpful, and indeed is often harmful, to patients and hence cannot be justified no matter what the source or kind of reasons used to support its use. Therefore, doctors may legitimately refuse to provide such treatments, so long as they do so for acceptable clinical reasons. They must also offer alternatives, including second (and third) opinions, as well the option of transferring the care of the patient to a more accommodating physician or institution.

When Religious Language Blocks Discussion About Health Care Decision Making Abstract There is a curious asymmetry in cases where the use of religious language involves a breakdown in communication and leads to a seemingly intractable dispute. Why does the use of religious language in such cases almost always arise on the side of patients and their families, rather than on the side of clinicians or others who work in healthcare settings? I suggest that the intractable disputes arise when patients and their families use religious language to frame their problem and the possibilities of solution. Unlike clinicians, they are not bilingual and thus lack the capacity to understand and negotiate differences in terms that are responsive to those who work in healthcare settings. After considering a representative case, I explore whether an ethics consultant or chaplain can function as a translator and suggest that, at best, such efforts at mediation depend on contingent aspects of a case and will only be partially successful. To appreciate limits on the role for bilingual translators, I consider a futility dispute where a parent using religious language demands that everything be done for a permanently unconscious child. I challenge the traditional interpretation that says the parent values "mere duration of biological life irrespective of quality." From a religious perspective, human life is never "merely biological." This effort to slot the dispute into standard philosophical schemas misses what is crucial in the dispute. I suggest that a better interpretation views the dispute at a meta-level as one about whether withholding and withdrawing care is morally distinguishable from killing. Curiously, this interpretation makes the advocate of futile care into an ally of those "quality of life" advocates who also challenge this distinction. The crux of their dispute now rests on the normative ethics of killing. While I think my interpretation comes much closer to the views of many who demand 'futile care,' I suggest that it still falls short because of the way it reconstructs the religious concerns in nonreligious terms. I close by considering an analogy between the language of suffering and the language of faith, suggesting that both require a much richer understanding of the narratives that orient the lives of patients and their families.

Integrative Clinical Ethics Support in Gender Affirmative Care: Lessons Learned Abstract Clinical ethics support (CES) for health care professionals and patients is increasingly seen as part of good health care. However, there is a key drawback to the way CES services are currently offered. They are often performed as isolated and one-off services whose ownership and impact are unclear. This paper describes the development of an integrative approach to CES at the Center of Expertise and Care for Gender Dysphoria (CEGD) at Amsterdam University Medical Center. We specifically aimed to integrate CES into daily work processes at the CEGD. In this paper, we describe the CES services offered there in detail and elaborate on the 16 lessons we learned from the process of developing an integrative approach to CES. These learning points can inform and inspire CES professionals, who wish to bring about greater integration of CES services into clinical practice.

Talking the Talk: Enhancing Clinical Ethics with Health Literacy Best Practices Abstract A significant proportion of the U.S. population exhibits low health literacy. Evidence suggests that low health literacy is correlated with higher medical costs and poorer health outcomes. Even more concerning, evidence suggests that low health literacy threatens patients' and families' autonomy and exacerbates injustices in patients who are already vulnerable to difficulties navigating the health care system. There is also, however, increasing evidence that health literacy interventions—including initiatives such as plain language practices and teach-back—improve comprehension and usefulness of health care information. I show how health literacy best practices can enhance the work of clinical ethicists in their primary roles of policy, consultation, and education. In the final section, I suggest ways health literacy initiatives may be enhanced with insights from clinical ethicists.

Professionalism: An Archaeology Abstract For more than two decades, classes on "professionalism" have been the dominant platform for the non-technical socialization of medical students. It thus subsumes elements of previous foundation courses in bioethics and "medicine and society" in defining the appropriate relation between practitioners, patients, and society-at-large. Despite its importance, there is, however, no clear definition of what "professionalism" entails or the manner in which it serves various purported goals. This essay reviews, first, the historical role of the vocational practitioner in society, and second, the introduction of "professionalism" as a newly constituted, core value in teaching. The structure of the paper is as an archaeology, a Foucauldian term for an investigation of seemingly separate but related antecedent contexts and ideas whose result is a perspective or point of view. The goal thus is an attempt to precisely locate "professionalism" within the greater history of medicine and its contemporary role in medical socialization.

Parental Decision Making: The Best Interest Principle, Child Autonomy, and Reasonableness Abstract On what basis should we judge whether a parent's medical decision for their child is morally acceptable? In a recent article, Johan Bester attempts to answer this question by defending a version of the Best Interest Standard (BIS) for parental decision making. The purpose of this paper is to identify a number of problems faced by Bester's version of BIS and to suggest ways to redress these problems. Accordingly, we intend to advance the project of formulating a method for guiding parents' medical decision making for their children. We argue that Bester's standard fails to accommodate the autonomy of the child and that his criteria for assessing the reasonableness of the parents' argument for their decision is too weak. We conclude that properly addressing these worries renders his test otiose and that it ought to be replaced with the three commonly held principles of bioethics—the principles of autonomy, beneficence, non-maleficence—and a standard of reasonableness.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Epidemiology

Nosology expansion: not always for health's sake

Prevalence of overweight and obesity in Western countries: discrepancies in published estimates Abstract Two papers were extracted and pooled data from published sources were used to estimate the distribution of BMI values for adults living in many countries around the world. The NCD Risk Factor Collaboration and the Global Burden of Disease Study 2013 presented data for 200 and 188 countries, respectively. We extracted estimates from the two datasets for the prevalences of overweight and obesity in 28 Western countries. The two studies used similar methodology for extracting and pooling data, however the papers show serious discrepancies in several countries. Our analysis reveals the need for increased standardization of the identification and analysis of surveys of BMI distribution. This is necessary in order to facilitate comparability of study results and accurate global monitoring of obesity trends. Our findings also indicate that if findings from Western countries contain serious discrepancies, then findings from middle-income and low-income countries will likely have a poor level of accuracy as far fewer surveys of BMI distribution have been carried out.

Maternal nut intake in pregnancy and child neuropsychological development up to 8 years old: a population-based cohort study in Spain Abstract There is scientific evidence on the protective effects of nut intake against cognitive decline in the elderly; however, this effect has been less explored in child neurodevelopment and no studies have explored the potential longitudinal association with nut intake during pregnancy. We aimed to analyze the association of maternal nut intake during pregnancy with child neuropsychological outcomes. We included 2208 mother–child pairs from a population-based birth cohort in four regions of Spain. The follow up settings were during pregnancy (first and third trimesters), birth, 1.5, 5 and 8 years. Neuropsychological examinations were based on Bayley Scales of Infant Development (1.5 years), McCarthy scales of Children's Abilities (5 year), Attention Network Test (ANT, 8 year) and N-Back test (8 year). Nut intake in pregnancy was reported through a validated food frequency questionnaire during the first and the third trimester. Multivariable regressions analyzed associations after controlling for priori selected confounders notably maternal education, social class, body mass index, energy intake, fish intake, omega-3 supplements, alcohol consumption and smoking habits during pregnancy. Children within the highest tertile of maternal nut consumption during first pregnancy trimester (> 32 g/week) had a decrease of 13.82 ms [95% confidence interval (CI) − 23.40, − 4.23] in the ANT—hit reaction time standard error, compared to the first tertile (median 0 g/w). A similar protective association pattern was observed with the other cognitive scores at the different child ages. After correcting for multiple testing using Bonferroni familywise error rate (FWER), Hochberg FWER and Simes false discovery rate, ANT—hit reaction time standard error remained significant. Final model estimates by inverse probability weighting did not change results. Third pregnancy trimester nut intake showed weaker associations. These data indicate that nut intake during early pregnancy is associated with long-term child neuropsychological development. Future cohort studies and randomized clinical trials are needed to confirm this association pattern in order to further extend nutrition guidelines among pregnant women.

Expanding disease and undermining the ethos of medicine Abstract The expansion of the concept of disease poses problems for epidemiology. Certainly, new diseases are discovered and more people are treated earlier and better. However, the historically unprecedented expansion is criticised for going too far. Overdiagnosis, overtreatment, and medicalization are some of the challenges heatedly debated in medicine, media, and in health policy making. How are we to analyse and handle the vast expansion of disease? Where can we draw the line between warranted and unwarranted expansion? To address this issue, which has wide implications for epidemiology, we need to understand how disease is expanded. This article identifies six ways that our conception of disease is expanded: by increased knowledge (epistemic), making more phenomena count as disease (ontological), doing more (pragmatic), defining more (conceptual), and by encompassing the bad (ethic) and the ugly (aesthetic). Expanding the subject matter of medicine extends its realm and power, but also its responsibility. It makes medicine accountable for ever more of human potential dis-eases. At the same time it blurs the borders and undermines the demarcation of medicine. Six specific advices can guide our action clarifying the subject matter of medicine in general and epidemiology in particular. To avoid unlimited responsibility and to keep medicine on par with its end, we need to direct the expansion of disease to what effectively identifies or reduces human suffering. Otherwise we will deplete medicine and undermine the greatest asset in health care: trust.

Being born in the aftermath of World War II increases the risk for health deficit accumulation in older age: results from the KORA-Age study Abstract Morbidity trends may result from cohort experiences in critical developmental age. Our objective was to compare the health status of 65–71 year-olds who were in critical developmental age before (1937–June 1945), during (June 1945–June 1948) and after (June 1948–1950) the early reconstruction and food crisis (ERFC) period in Germany following World War II. Data originate from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study in Southern Germany. We used the 2008 baseline sample born 1937–1943 and the 2015 enrichment sample born 1944–1950. Health status was assessed as the number of accumulated health deficits using a Frailty Index (FI). Cohorts were defined based on co-occurrence of critical developmental age (gestation and the first 2 years of life) and the ERFC period. Cohort, age and sex effects on older-age health status were analyzed using generalized linear models. We included 590 (53% male) pre-war and war (PWW), 475 (51% male) ERFC and 171 post-currency reform (PCR) cohort participants (46% male). Adjusted for covariates, FI levels were significantly higher for the ERFC (Ratio 1.14, CL [1.06, 1.23]) but not for the PCR (Ratio 1.06, CL [0.94, 1.20]) as compared to the PWW cohort. Being in critical developmental age during the ERFC period increased FI levels in adults aged 65–71 years. Covariates did not explain these effects, suggesting a direct detrimental effect from being in critical developmental age during the ERFC period on older-age health. This expansion of morbidity in Germany was not detected in the PCR cohort.

Smoking in pregnancy, cord blood cotinine and risk of celiac disease diagnosis in offspring Abstract Ecological observations suggest an inverse relationship between smoking in pregnancy and celiac disease (CD) in offspring. While individual-level analyses have been inconsistent, they have mostly lacked statistical power or refined assessments of exposure. To examine the association between pregnancy-related smoking and CD in the offspring, as well as its consistency across data sets, we analyzed: (1) The Norwegian Mother and Child Cohort (MoBa) of 94,019 children, followed from birth (2000–2009) through 2016, with 1035 developing CD; (2) a subsample from MoBa (381 with CD and 529 controls) with biomarkers; and (3) a register-based cohort of 536,861 Norwegian children, followed from birth (2004–2012) through 2014, with 1919 developing CD. Smoking behaviors were obtained from pregnancy questionnaires and antenatal visits, or, in the MoBa-subsample, defined by measurement of cord blood cotinine. CD and potential confounders were identified through nationwide registers and comprehensive parental questionnaires. Sustained smoking during pregnancy, both self-reported and cotinine-determined, was inversely associated with CD in MoBa (multivariable-adjusted [a] OR = 0.61 [95%CI, 0.46–0.82] and aOR = 0.55 [95%CI, 0.31–0.98], respectively); an inverse association was also found with the intensity of smoking. These findings differed from those of our register-based cohort, which revealed no association with sustained smoking during pregnancy (aOR = 0.97 [95%CI, 0.80–1.18]). In MoBa, neither maternal smoking before or after pregnancy, nor maternal or paternal smoking in only early pregnancy predicted CD. In a carefully followed pregnancy cohort, a more-detailed smoking assessment than oft-used register-based data, revealed that sustained smoking during pregnancy, rather than any smoking exposure, predicts decreased likelihood of childhood-diagnosed CD.

Maternal proximity to extremely low frequency electromagnetic fields and risk of birth defects Abstract Causes of birth defects are unclear, and the association with electromagnetic fields is inconclusive. We assessed the relationship between residential proximity to extremely low frequency electromagnetic fields from power grids and risk of birth defects. We analyzed a population-based sample of 2,164,246 infants born in Quebec, Canada between 1989 and 2016. We geocoded the maternal residential postal code at delivery and computed the distance to the nearest high voltage electrical transmission line or transformer station. We used log-binomial regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of residential proximity to transmission lines and transformer stations with birth defects, adjusting for maternal and infant characteristics. The prevalence of birth defects within 200 m of a transmission line (579.4 per 10,000 per live births) was only slightly higher compared with distances further away (568.7 per 10,000). A similar trend was seen for transformer stations. Compared with 200 m, a distance of 50 m was not associated with the risk of birth defects for transmission lines (RR 1.00, 95% CI 1.00–1.01) and transformer stations (RR 1.01, 95% CI 1.00–1.03). There was no consistent association when we examined birth defects in different organ systems. We found no compelling evidence that residential proximity to extremely low frequency electromagnetic fields from electrical power grids increases the risk of birth defects. Women residing near electrical grids can be reassured that an effect on the risk of birth defects is unlikely.

Night shift work before and during pregnancy in relation to depression and anxiety in adolescent and young adult offspring Abstract We investigated the relationship between maternal history of nightshift work before and shift work during pregnancy and offspring risk of depression and anxiety, among mothers participating in the Nurses Health Study II and in their offspring enrolled in the Growing Up Today Study 2 between 2004 and 2013. Case definitions were based on offspring self-reports of physician/clinician-diagnosed depression and/or anxiety, regular antidepressant use and depressive symptoms assessed using the Center for Epidemiologic Studies Depression Scale. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using generalized estimating equation models. We found no associations between maternal nightshift work before pregnancy or during pregnancy and offspring mental health disorders (e.g., nightshift work before pregnancy: depression (based on physician/clinician diagnosis): ORever nightwork = 1.14; 95% CI, 0.88–1.47; either depression or anxiety: ORever nightwork = 0.93; 95% CI, 0.81–1.08; nightshift work during pregnancy: depression: ORever nightwork = 1.14; 95% CI, 0.68–1.94; depression or anxiety: ORever nightwork =1.17; 95% CI, 0.70–1.98) and no dose-response relationship with longer history of nightshift work (all PTrend  >0.10). Stratifying by maternal chronotype revealed a higher risk of depression for offspring whose mothers worked nightshifts before pregnancy and reported being definite morning chronotypes (a proxy for circadian strain) (ORever nightwork = 1.95; 95% CI, 1.17, 3.24 vs. ORever nightwork = 0.93; 95% CI, 0.68, 1.28 for any other chronotype; PInteraction = 0.03). Further studies replicating our findings and refined understanding regarding the interplay of nightshift work and chronotype and its potential influences on offspring mental health are needed.

Missing girls among deliveries from Indian and Chinese mothers in Spain 2007–2015 Abstract Deliveries from Indian and Chinese mothers present a higher than expected male:female ratio in their own countries, in northern Europe, EEUU and Canada. No studies have been carried out in southern European countries. We explored whether the high male-to-female ratio common in Indian and Chinese communities, also exists among families from those regions who live in Spain. For that purpose we designed a cross-sectional population-based study containing data on 3,133,908 singleton live births registered in the Spanish Vital Statistics Registry during the period 2007–2015. The ratio of male:female births by area of origin was calculated using binary intercept-only logistic regression models without reference category for the whole sample of births and taking into account a possible effect modification of birth order and sex of the previous males. Interaction effects of sociodemographic mothers' and fathers' characteristics was also assesed. In Spain, the ratio male:female is higher than expected for Indian-born mothers, especially for deliveries from mothers with no previous male births and, to a lesser extent, for Chinese-born women, specifically for third or higher order births and slightly influenced by the sex of the previous births. Therefore, the increased sex male:female ratio observed in other countries among Indian and Chinese mothers is also observed in Spain. This reinforces the notion that culture and values of the country of origin are more influential than the country of residence.

Preconceptional paternal antiepileptic drugs use and risk of congenital anomalies in offspring: a nationwide cohort study Abstract Recent studies have shown that certain pharmacological agents used by fathers before conception may increase the risk of adverse neonatal outcomes in offspring. However, little is known about the effect of paternal use of antiepileptic drugs (AEDs) on congenital anomalies in children. Based on Danish national registers, we conducted a cohort study of 733, 282 singletons born from 1997 to 2008, with follow-up throughout 2013. The children whose fathers used AEDs during the 3 months before conception were categorized as the exposed. Logistic regression model was used to examine association between paternal AEDs use before conception and the risk of congenital anomalies in offspring. Compared with unexposed children, the exposed had a 23% increased risk of congenital anomalies (odds ratios (OR) 1.23, 95% confidence interval [CI] 1.10–1.37) after adjusting for potential confounders. When extending the exposure window to 1 year before conception to the end of pregnancy, except for those using AEDs during 3 months before conception (the susceptible period of exposure), the increased risks were also observed in children whose fathers were former users (i.e., those using AEDs only from 1 year to 3 months before conception) (OR 1.29, 95%CI 1.03–1.61) and later users (i.e., those using AEDs only during pregnancy) (OR 1.35, 95%CI 1.12–1.65). This study suggested that the mildly increased risk of congenital anomalies in the offspring associated with paternal AEDs use before conception may be attributable to the underlying indications related to AEDs use.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Molecular Diagnosis & Therapy

First Responder to Genomic Information: A Guide for Primary Care Providers Abstract With rapid advances in genetics and genomics, the commercialization and access to new applications has become more widespread and omnipresent throughout biomedical research. Thus, increasingly, more patients will have personal genomic information they may share with primary care providers (PCPs) to better understand the clinical significance of the data. To be able to respond to patient inquiries about genomic data, variant interpretation, disease risk, and other issues, PCPs will need to be able to increase or refresh their awareness about genetics and genomics, and identify reliable resources to use or refer patients. While provider educational efforts have increased, with the rapid advances in the field, ongoing efforts will be needed to prepare PCPs to manage patient needs, integrate results into care, and refer as indicated.

A Novel Modified System of Simplified Chinese Criteria for Familial Hypercholesterolemia (SCCFH) Abstract Background and Objective The most significant clinical implication of familial hypercholesterolemia (FH) is early-onset coronary artery disease (CAD), highlighting the importance of a definitive diagnosis being available. Unfortunately, the existing algorithms are complex and it is often difficult to obtain information on the patient's family history. Hence, we aimed to establish a novel system of Simplified Chinese Criteria for FH (SCCFH). Methods We recruited 12,921 participants undergoing routine blood collection from November 2011 to June 2018. Clinical characteristics, laboratory examination, and genetic testing were obtained. FH was diagnosed based on the Simon Broome (SB) criteria, Dutch Lipid Clinic Network (DLCN) criteria, and SCCFH. The sensitivity, specificity, and agreement of SCCFH to these existing criteria were investigated. Results Of 12,921 participants reviewed, the prevalence of definite FH was 223 (1.73%), 202 (1.56%), and 205 (1.59%) based on the DLCN, SB, and SCCFH approaches, respectively. Compared with the DLCN and SB criteria, the SCCFH showed high sensitivity (91.9% and 100%), high specificity (100% and 99.9%), and good agreement (κ = 0.958 and 0.993). Similar results were found in several relevant clinical subgroups. Conclusions The SCCFH system is comparable to the existing criteria with high levels of sensitivity and specificity, and is easier to use clinically. Further larger prospective studies are needed to evaluate the feasibility and reliability of this system.

Overexpression of S100A4 Predicts Migration, Invasion, and Poor Prognosis of Hypopharyngeal Squamous Cell Carcinoma Abstract Introduction Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck and frequently involves regional metastasis. However, the mechanism underlying the aggressiveness of HSCC remains elusive. S100A4 is a well-established metastasis-promoting regulator in a variety of malignancies, but its role in HSCC has not yet been identified. Objectives Our objectives were to explore the expression levels of S100A4 in HSCC tumors and its association with clinicopathological parameters and the clinical prognosis of HSCC and to confirm its role in the metastatic process of the HSCC FaDu cell line in vitro. Methods We assessed the expression levels of S100A4 with immunohistochemistry (IHC) in HSCC tumors (n = 71) and adjacent normal tissues (n = 44). In vitro experiments were performed to explore the impact of S100A4 knockdown on biological phenotypes of human HSCC FaDu cell line, including migration, invasion, proliferation, apoptosis, and cell cycle. Results The expression of S100A4 was elevated in HSCC tumors compared with adjacent normal tissues and positively correlated with cervical lymph node metastasis in this HSCC patient cohort. In vitro experiments showed that S100A4 knockdown significantly impaired migration and invasion and increased the proportion of cells in G0/G1 phase with no change in proliferation or apoptosis in FaDu cells. Additionally, nuclear S100A4 expression proved to be an independent prognostic indicator in patients with HSCC. Conclusion This study demonstrated for the first time that S100A4 expression is upregulated in HSCC tumors and that this upregulation is positively correlated with cervical lymph node metastasis of this malignancy. The metastasis-promoting role of S100A4 was further validated in the HSCC FaDu cell line, indicating that S100A4 is a potential therapeutic target for HSCC. Furthermore, this study suggests that nuclear S100A4 expression could be considered a prognostic biomarker for HSCC.

Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis Abstract Background Thiopurine S-methyltransferase (TPMT) testing, either by genotyping or phenotyping, can reduce the incidence of adverse severe myelotoxicity episodes induced by azathioprine. The comparative cost-effectiveness of TPMT genotyping and phenotyping are not known. Objective Our aim was to assess the cost-effectiveness of phenotyping-based dosing of TPMT activity, genotyping-based screening and no screening (reference) for patients treated with azathioprine. Methods A decision tree was built to compare the conventional weight-based dosing strategy with phenotyping and with genotyping using a micro-simulation model of patients with inflammatory bowel disease from the perspective of the French health care system. The time horizon was set up as 1 year. Only direct medical costs were used. Data used were obtained from previous reports, except for screening test and admission costs, which were from real cases. The main outcome was the cost-effectiveness ratios, with an effectiveness criterion of one averted severe myelotoxicity episode. Results The total expected cost of the no screening strategy was €409/patient, the total expected cost of the phenotyping strategy was €427/patient, and the total expected cost of the genotyping strategy was €476/patient. The incremental cost-effectiveness ratio was €2602/severe myelotoxicity averted in using the phenotyping strategy, and €11,244/severe myelotoxicity averted in the genotyping strategy compared to the no screening strategy. At prevalence rates of severe myelotoxicity > 1%, phenotyping dominated genotyping and conventional strategies. Conclusion The phenotype-based strategy to screen for TPMT deficiency dominates (cheaper and more effective) the genotype-based screening strategy in France. Phenotype-based screening dominates no screening in populations with a prevalence of severe myelosuppression due to azathioprine of > 1%.

Aptamers as Therapeutic Agents: Has the Initial Euphoria Subsided? Abstract Aptamers are synthetic DNA or RNA oligonucleotide ligands with great potential for therapeutic applications. A vast number of disease-related targets have been used to identify agonistic, antagonistic, or inhibitory aptamers, or aptamer-based targeting ligands. However, only a few aptamers have reached late-stage clinical trials so far and the commercial infrastructure is still far behind that of other therapeutic agents such as monoclonal antibodies. The desirable properties of aptamers such as selectivity, chemical flexibility, or cost-efficiency are faced by challenges, including a short half-life in vivo, immunogenicity, and entrapment in cellular organelles. Aptamer research is still in an early stage, and a deeper understanding of their structure, target interactions, and pharmacokinetics is necessary to catch up to the clinical market. In this review, we will discuss the benefits and limitations in the development of therapeutic aptamers, as well as the advances and future directions of aptamer research. The progress towards effective therapies seems to be slow, but it has not stopped and the best is yet to come.

Clinicopathological Features of ALK Expression in 9889 Cases of Non-small-Cell Lung Cancer and Genomic Rearrangements Identified by Capture-Based Next-Generation Sequencing: A Chinese Retrospective Analysis Abstract Background The clinicopathological features and genomic rearrangements of anaplastic lymphoma kinase (ALK) fusion cases have not been fully identified. Objective Our objective was to explore the status of ALK in non-small-cell lung cancer (NSCLC) specimens, to explore the relationships between ALK status and clinicopathological features and to identify genomic rearrangements via capture-based next-generation sequencing (NGS). Methods We tested 9889 NSCLC specimens for ALK status using the Ventana anti-ALK (D5F3) antibody. Clinicopathological features were analyzed and genomic rearrangements identified using capture-based NGS in 76 ALK-positive cases. Results In total, 485 specimens (4.90%) tested positive for ALK. The positivity rate was higher for adenocarcinoma samples than for non-adenocarcinoma samples (6.03 vs. 1.47%; p < 0.001) and for biopsies/cell blocks than for surgical specimens (7.00 vs. 4.16%; p < 0.001). Patient age, patient sex, specimen type, specimen histotype, and patient smoking history were all significantly correlated with ALK status. Genomic rearrangements were detected in 98.68% (75/76) of the ALK-positive samples; 89.33% (67/75) carried the canonical EML4-ALK, and the remaining samples carried only noncanonical ALK rearrangements. Four of these noncanonical ALK fusion samples were identified as carrying EML4-ALK transcripts at the RNA level. A novel fusion variant, SRD5A2-ALK, was revealed. Conclusions Younger patients with NSCLC, especially those aged < 30 years, were more likely to test positive for ALK. Positive ALK test results were more common in patients with invasive mucinous adenocarcinoma and solid-predominant invasive adenocarcinoma than in patients with other histotypes. Samples that carried only noncanonical ALK rearrangements may also have carried the canonical EML4-ALK, which was not detected by capture-based NGS. EML4-ALK transcripts might result from rare splicing mechanisms without genomic rearrangements.

Advances in Detection of Kidney Transplant Injury Abstract Early detection of graft injury after kidney transplantation is key to maintaining long-term good graft function. Graft injury could be due to a multitude of factors including ischaemia reperfusion injury, cell or antibody-mediated rejection, progressive interstitial fibrosis and tubular atrophy, infections and toxicity from the immunosuppressive drugs themselves. The current gold standard for assessing renal graft dysfunction is renal biopsy. However, biopsy is usually late when triggered by a change in serum creatinine and of limited utility in diagnosis of early injury when histological changes are equivocal. Therefore, there is a need for timely, objective and non-invasive diagnostic techniques with good early predictive value to determine graft injury and provide precision in titrating immunosuppression. We review potential novel plasma and urine biomarkers that offer sensitive new strategies for early detection and provide major insights into mechanisms of graft injury. This is a rapidly expanding field, but it is likely that a combination of biomarkers will be required to provide adequate sensitivity and specificity for detecting graft injury.

Clinicopathological Significance of Overall Frequency of Allelic Loss (OFAL) in Lesions Derived from Thyroid Follicular Cell Abstract Background Loss of heterozygosity (LOH) and microsatellite instability (MSI) are frequent molecular events in thyroid tumor etiopathogenesis occurring in several chromosomal critical areas, including 3p12–25.3, 7q21–31, 10q22–24, and 15q11–13, with loci of tumor suppressor genes. Objective We evaluated the usefulness of LOH/MSI as a diagnostic/prognostic biomarker in lesions derived from thyroid follicular cells: follicular thyroid carcinoma (FTC); follicular adenoma (FA), papillary thyroid carcinoma (PTC), and nodular goiter (NG). Methods We performed allelotyping (GeneMapper Software v. 4.0.) of ten microsatellite markers linked to the 1p31.2, 3p21.3, 3p24.2, 9p21.3, 11p15.5, and 16q22.1 region on DNA from 93 primary thyroid lesions then evaluated the LOH/MSI frequency and overall frequency of allelic loss (OFAL). Results We found regions with significantly increased frequency of LOH/MSI for specific histotypes: the 3p24.2 region for FA and 1p31.2 for FTC. LOH/MSI in 3p21.3 was significantly elevated in PTC and FTC. LOH/MSI in 3p21.3 was increased for small size tumors (T1a + T1b), tumors with no regional lymph node involvement (N0 + Nx), American Joint Committee on Cancer (AJCC) stage I tumors, and tumor diameter (Td) < 10 mm; in 1p31.2 for T2–3, N1, stage II–IV, and Td 10–30 mm; in 11p15.5 for T2–3, N1, stage II–IV, and Td > 30 mm. OFAL values were significantly higher in younger patients (< 40 years), in men, in those with T2–3 stage tumors, in those with increased Td, and in FA and FTC compared with NG and PTC. Conclusions We confirmed the occurrence of LOH/MSI in 3p21.3 at an early stage of tumorigenesis and mapped 1p31.2 and 11p15.5 as characteristic for advanced-stage tumors. The results of our study may enable consideration of OFAL, defined as LOH/MSI coincidence in various chromosomal regions, as a tumor progression marker. OFAL values were significantly higher in follicular neoplasms (FA and FTC) than in PTC or NG; hence, increased OFAL values can be regarded as a characteristic feature of the follicular phenotype.

Vortex- and Centrifugation-Free Extraction of HIV-1 RNA Abstract Background and Objective HIV viral load measurements play a critical role in monitoring disease progression in those who are on antiretroviral treatment. In order to obtain an accurate measurement, rapid sample preparation techniques are required. There is an unmet need for HIV extraction instruments in resource-limited settings, where HIV prevalence is high. Therefore, the objective of our study was to develop a three-dimensional (3D) microfluidic system to extract HIV-1 RNA with minimal electricity and without complex laboratory instruments. Methods A 3D microfluidic system was designed in which magnetic beads bound with nucleic acids move through immiscible oil–water interfaces to separate HIV-1 RNA from the sample. Polymerase chain reaction (PCR) amplification was used to quantify the total amount of HIV-1 RNA extracted as we optimized the system through chip design, bead type, carry-over volume, carrier RNA concentration, and elution buffer temperature. Additionally, the extraction efficiency of the 3D microfluidic system was evaluated by comparing with a Qiagen EZ1 Advanced XL instrument using 20 HIV-1-positive plasma samples. Results Our method has near-perfect (100%) extraction efficiency in spiked serum samples with as little as 50 copies/mL starting sample. Furthermore, we report carry-over volumes of 0.31% ± 0.006% of total sample volume. Using the EZ1 Advanced XL as a gold standard, the average percentage HIV-1 RNA extracted using the microchip was observed to be 65.4% ± 24.6%. Conclusions From a clinical perspective, the success of our method opens up its possible use in diagnostic tests for HIV in the remote areas where access to vortexes and centrifuges is not available. Here we present a proof-of-concept device which, with further development, could be used for sample preparation at the point of care.

Mutational Landscape of Resistance to Thyroid Hormone Beta (RTHβ) Abstract Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by reduced responsiveness of peripheral tissues to thyroid hormone (TH). In most cases, the disorder is associated with germline pathogenic variants in the thyroid hormone receptor beta (THRB) gene. This paper summarizes the clinical and biochemical presentation of the disease, providing a comprehensive overview on molecular genetic features. Particular care is given in reporting all identified THRB variants with an assessed or unknown clinical significance. Our aim is to offer a useful tool for clinical and genetic specialists in order to ease clinical diagnosis and genetic counseling.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com