Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Experiences of Awe and Gratitude and Related Triggers Among Religious Brothers and Sisters: Findings from a Cross-Sectional Study in Germany.

A cross-sectional survey among religious brothers and sisters (n = 250) with their specific lifestyle and related spiritual practices stated moments of awe perceptions. They responded to both the Awe/Gratitude scale and to free text fields to substantiate their quantitative responses. Qualitative content analysis of their free text responses resulted in six main categories of awe triggers: (1) Nature, (2) Special Moments, (3) Transcendence Perceptions, (4) Religious practices, (5) Distinct People, and (6) Aesthetics, Art and Culture. Awe perceptions can be an immediate feeling and the outcome of a process of reflection in response to admiration, inspiration, and elevation. As these perceptions are related to psychological well-being and prosocial behaviors, their training can generate positive effects on quality of life.

Inner Peace needs of male psychiatric patients in post-war Croatia are associated with their needs to clarify open issues in their life and their needs for forgiveness.

Background: More than 25 years after the end of the Balkan war, many people belonging to the post-war population are still traumatized by the war events and have been treated for post-traumatic stress disorder or other psychiatric diagnoses. We were interested in their Inner Peace needs, how these relate to indicators of mental health, and their needs to clarify open processes in their lives and to forgive and be forgiven. Materials and methods: In a cross-sectional survey with standardized questionnaires (i.e., SpNQ, PCL-M, HADS, and BMLSS), 638 male patients who were treated in seven psychiatric centers in Croatia were enrolled. 68% were diagnosed with PTSD and 32% had other psychiatric diagnoses. Most had actively participated in the Balkan war (79%), and 60% for the whole war period. Results: Strong needs to "immerse into beauty of nature" were stated by 47%, to "dwell at a place of quietness and peace" by 66%, and to "find inner peace" by 57%. These Inner Peace needs were highest in men treated with PTSD diagnoses as compared to men with other psychiatric diagnoses and were slightly lower in men who were active during the whole war period as compared to shorter phases of war participation. Regression analyses with Inner Peace needs as a dependent variable revealed that Clarification/Forgiveness needs were the best predictor, with further influences of PTSD symptoms and life satisfaction, explaining altogether 49% of the variance. The best predictors of their PTSD symptoms were life satisfaction, perceived burden, depressive symptoms, Inner Peace needs, religious trust, and duration of war participation, explaining 60% of the variance. Conclusion: In Croatian male war participants in clinical treatment decades after the war, Inner Peace needs indicate their ongoing intention to let go of their disturbing experiences and to find states of inner peace, particularly at specific places of quietness and peace. These needs can be considered metaphors for longing for wholeness, integrity, and safety, in contrast to the ongoing impact of unresolved issues. Thus, apart from psychotherapeutic treatment, sheltered places of nature, inspiration, and reconciliation might be elements to improve the difficult situation of post-war victims still suffering from their experiences.

Experience of loss and grief among people from Germany who have lost their relatives during the pandemic: the impact of healthcare professionals' support.

Background: Due to public restrictions during the early stages of the COVID-19 pandemic, many people were unable to visit and bid a proper farewell to their dying loved ones. This study aimed to address the loss-oriented aspects of grief and bereavement of relatives and relate these to the support they may have received from their dying relative's caring professionals. Materials and methods: People from Germany who experienced bereavement during the COVID-19 pandemic were enrolled in a cross-sectional study between July 2021 and May 2022, using standardized questionnaires (i.e., ICG, Inventory of Complicated Grief; BGL, Burdened by Grief and Loss scale; WHO-5, WHO-Five Wellbeing Index; and 5NRS, perception of burden related to the pandemic). Results: Most participants (n = 196) had the opportunity to visit their relatives before death (59%). When this was not possible, being burdened by grief and loss was significantly higher (Eta2 = 0.153), while this had no significant influence on complicated grief or psychological wellbeing. Furthermore, 34% of participants felt well-supported by the treatment/care team. Their own support was moderately correlated with BGL scores (r = -0.38) and marginally with ICG scores (r = -15). Regression analyses showed that complicated grief symptoms as the dependent variable were predicted by (low) psychological wellbeing, relational status, and the perception of COVID-19-related burden (R2 = 0.70). In contrast, BGL as the dependent variable can be best explained by the perception of emotional affections because of restricted visits shortly before their death, by the (short) duration of visits before death, and by the relational status (R2 = 0.53). Although both were interconnected (r = 0.44), their predictor pattern was different. Conclusion: Being able to visit dying relatives was important for the mourning and bereavement processes. This emotional aspect was more relevant to the normal, non-pathological grief and loss processes than to complicated grief processes. Support from their dying relatives' treatment/care team was highly relevant to the mourning process, but the visiting relatives often lacked information about additional resources such as psychologists or pastoral care professionals or had limited access to them.

Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

BACKGROUND: The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer. METHODS: In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose. RESULTS: Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD. CONCLUSIONS: In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen.

Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial.

PURPOSE: To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer. METHODS: In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability. RESULTS: Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab. CONCLUSION: Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.

Experience of nature and times of silence as a resource to cope with the COVID-19 pandemic and their effects on psychological wellbeing-Findings from a continuous cross-sectional survey in Germany.

Background: The COVID-19 pandemic with its lockdowns affected social relations and mental health conditions of people worldwide. We aimed to analyze the relevance of nature and times of silence as resources to cope with the pandemic. Of interest were how experiences of nature and times of silence are related to the perception of wondering awe and gratitude and psychological wellbeing and how these have changed during the different phases of the pandemic. Finally, we asked whether Nature/Silence would mediate the link between Awe/Gratitude and wellbeing. Methods: A cross-sectional survey with standardized questionnaires (i.e., PCQ, GrAw-7, BMLSS-10, WHO-5) enrolling participants during the different phases of the COVID-19 pandemic was conducted. The total sample of 5,155 participants from Germany consisted of 65% women and 34% men, with a mean age of 45.0 ± 14.0 years. Results: Directly after the first lockdown, Nature/Silence and Awe/Gratitude scores were high and decreased along with wellbeing with the onset of the second lockdown in winter 2020, while perceived burden constantly increased. Nature/Silence was rated lowest by people with reduced wellbeing (eta2 = 0.058) and feeling lonely or socially isolated (eta2 = 0.042). Predictor analyses revealed that wellbeing as a dependent variable was predicted best by corona-related perception of burden, Awe/Gratitude, reflection of life, and Nature/Silence and further by perceived changes in terms of relationships and spirituality (R2 = 0.55). In mediation analyses, Awe/Gratitude proved to be a significant predictor for Nature/Silence (ß = 0.55, p< 0.0001) and wellbeing (ß = 0.05, p < 0.0001). The mediation analysis explained 37% of the variability in the data. The direct influence of Awe/Gratitude on wellbeing was estimated as ß = 0.09 (p < 0.0001), and the mediation effect of Nature/Silence on the link between Awe/Gratitude and wellbeing was significant, too (ß = 0.03, p < 0.0001), explaining 25% of the total effect. Conclusion: Nature/Silence and Awe/Gratitude were used as relevant resources during the pandemic, although they cannot fully buffer the negative effects of the social restrictions that resulted in decreases in wellbeing and increases in perceived burden. Perception of nature as a sensitizer of positive experiences particularly during difficult phases of life could be trained to stabilize wellbeing and thus to contribute to public health.

Cross-cultural validity of the Death Reflection Scale during the COVID-19 pandemic.

Background: The global COVID-19 pandemic confronts people with their fragility, vulnerability, and mortality. To date, scales to measure death awareness mainly focus on the anxiety-provoking aspect of mortality cues. This study aims to cross-culturally adapt and validate the Death Reflection Scale (DRS), a scale for measuring positive, growth-oriented cognitions of life reflection and prosocial behavior following confrontation with the finiteness of life. Materials and Methods: The Death Reflection Scale was translated and adapted in a multi-step process to the German language. In this anonymous, cross-sectional, online survey at a large university in Germany, students, healthcare professionals (HCP) and other staff completed the DRS alongside comparison measures. Multi-group confirmatory factor analysis was used to assess configural, metric, and scalar measurement equivalence across four age and occupational groups. Convergent/divergent validity testing was done via Spearman correlations. Results: 1,703 participants provided data for a response rate of ∼5%. 24% of respondents were HCP, 22% students. Confirmatory factor analysis showed a higher-order structure of the DRS with a strong general factor and the originally proposed five subscales (CFI 0.945, SRMR 0.045, RMSEA 0.055). Multi-group CFA showed partial metric equivalence across age groups and partial scalar invariance across occupational groups. Non-invariant scales were the Motivation to live, Putting life into perspective, and Legacy subscales. In the convergent validity testing, two hypotheses were fully confirmed, two partially and four were not confirmed. Experiencing a propensity for increased contemplation and life reflection during the pandemic together with spirituality showed correlations of moderate to large size to the DRS and its subscales (Spearman's rho ranging from 0.31 to 0.52). Conclusion: Further conceptual work for death awareness to explore the construct's stability in different population groups needs to be undertaken. However, the DRS can be mostly used to assess positive and growth-oriented aspects of death awareness and death reflection which may be an important avenue when developing counseling and support interventions for groups experiencing a high burden during the pandemic.

Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant.

PURPOSE: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC. RESULTS: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538-0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458-0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b-expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446-0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359-0.775; P = 0.001), independently from established risk factors. CONCLUSIONS: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.

Impact of disease progression on health-related quality of life of advanced ovarian cancer patients - Pooled analysis from the PRIMA trial.

OBJECTIVE: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL.

Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population. RESULTS: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37). CONCLUSIONS: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.

Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study.

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Loss of Faith and Decrease in Trust in a Higher Source During COVID-19 in Germany.

Many people relied on their faith as one resource in order to cope during the COVID-19 pandemic. In Germany, between the eighteen months from June 2020 to November 2021, different participants at different times were assessed during different phases of the COVID-19 pandemic. The total sample of this continuous cross-sectional survey consisted of 4,693 participants. Analyses revealed that with the 2nd wave of the infection and its 2nd lockdown, trust in a Higher Source, along with praying and meditation decreased. Also, the sharp increase in corona-related stressors was associated with a decline of wellbeing and a continuing loss of faith. These developments were observed in both Catholics and Protestants, and in both younger and older persons. In addition, the long phases of insecurity and social isolation lacking the significant support usually given by religious communities may have likewise challenged the religious-coping capacities of religious/spiritual people themselves.

Clonal Hematopoiesis-Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer.

BACKGROUND: Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH-associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity. METHODS: We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH-associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided. RESULTS: Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH-associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH-associated gene mutations was observed. CONCLUSIONS: A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.

The NERSH Questionnaire and Pool of Data from 12 Countries: Development and Description.

Modern healthcare research has only in recent years investigated the impact of health care workers' religious and other values on medical practice, interaction with patients, and ethically complex decision making. So far, only limited international data exist on the way such values vary across different countries. We therefore established the NERSH International Collaboration on Values in Medicine with datasets on physician religious characteristics and values based on the same questionnaire. The present article provides (a) an overview of the development of the original and optimized questionnaire, (b) an overview of the content of the NERSH data pool at this stage and (c) a brief review of insights gained from articles published with the questionnaire. The pool at this stage consists of data from 17 studies from research units in 12 different countries representing six continents with responses from more than 6000 health professionals. The joint data pool suggests that there are large differences in religious and other moral values across nations and cultures, and that these values contribute to the observed differences in health professionals' clinical practices-across nations and cultures!

Adjuvant radiotherapy and local recurrence in vulvar cancer - a subset analysis of the AGO-CaRE-1 study.

BACKGROUND: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. PATIENTS AND METHODS: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. RESULTS: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). CONCLUSION: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV- tumors.

Health professionals' attitudes toward religiosity and spirituality: a NERSH Data Pool based on 23 surveys from six continents.

Background In order to facilitate better international and cross-cultural comparisons of health professionals (HPs) attitudes towards Religiosity and/or Spirituality (R/S) we updated the NERSH Data Pool. Methods We performed both a network search, a citation search and systematic literature searches to find new surveys. Results We found six new surveys (N=1,068), and the complete data pool ended up comprising 7,323 observations, including 4,070 females and 3,253 males. Most physicians (83%, N=3,700) believed that R/S had "some" influence on their patients' health (CI95%) (81.8%-84.2%). Similarly, nurses (94%, N=1,020) shared such a belief (92.5%-95.5%). Across all samples 649 (16%; 14.9%-17.1%) physicians reported to have undergone formal R/S-training, compared with nurses where this was 264 (23%; 20.6%-25.4%). Conclusions Preliminary analysis indicates that HPs believe R/S to be important for patient health but lack formal R/S-training. Findings are discussed. We find the data pool suitable as a base for future cross-cultural comparisons using individual participant data meta-analysis.

Physicians' religious/spiritual characteristics and their behavior regarding religiosity and spirituality in clinical practice: A meta-analysis of individual participant data.

BACKGROUND: Religiosity and/or spirituality (R/S) of physicians have been reported to inform behavior regarding religiosity and spirituality in clinical practice (R/S-B). Our aim was to study this association. METHODS: Building upon a large international data pool of physician values we performed network and systematic literature searches using Google Scholar, Web of Science, Embase, Medline, and PsycInfo. Measures for R/S and R/S-B were selected for comparability with existing research. We performed a two-stage IPDMA using R/S coefficients from sample-wise multiple regression analyses as summary measures. We controlled for age, gender, and medical specialty. An additional sub-analysis compared psychiatrists to non-psychiatrists. RESULTS: We found 11 eligible surveys from 8 countries (n = 3159). We found a positive association between R/S and R/S-B with an overall R/S coefficient of 0.65 (0.48-0.83). All samples revealed a positive association between R/S and R/S-B. Only 2 out of the 11 samples differed from the overall confidence interval. Psychiatrists had a higher degree of R/S-B, but associations with R/S did not differ compared to non-psychiatrists. CONCLUSIONS: We confirmed a significant association between R/S and R/S-B in this study. Despite large cultural differences between samples, coefficients remained almost constant when controlling for confounders, indicating a cultural independent effect of R/S on R/S-B, which to our knowledge has not been documented before.Such interaction can constitute both facilitators and barriers for high quality health care and should be considered in all aspects of patient and relationship-centered medicine.

Dynamics of Perceived Positive Changes and Indicators of Well-Being Within Different Phases of the COVID-19 Pandemic.

Background: During the COVID-19 pandemic, people reported about fears, depressive states, and phases of loneliness. However, there have also been positively experienced changes in terms of awareness of nature, reflection of life, more intensive relationships, meaningful digital media usage to connect with others, and interest in spirituality. We were interested in the dynamics of these indicators directly after the first lockdown, the summer months and during the second wave of the pandemic with its second lockdown, and how they relate to the perceived restrictions, fears, and worries. Method: Survey with standardized questionnaires, i.e., Perceived Changes Questionnaire, WHO-Five Well-being Index, Brief Multidimensional Life Satisfaction Scale, Awe/Gratitude scale. Participants were categorized as cohort 1 (June 2020; n = 1,333), cohort 2 (July to September 2020, n = 823), and cohort three (October 2020 to January 2021, n = 625). Results: Participants perceived changes in specific attitudes and behaviors, which have impacted their well-being and life satisfaction. Compared to their experiences directly after the first wave of the pandemic (cohort 1), well-being (Hedge's g = 0.83) and life satisfaction (g = 0.63) decreased during the second wave (cohort 3) and participants' stressors increased (g = -0.94). At the same time, positive perceptions such as Nature/Silence/Contemplation (g = 0.67), Spirituality (g = 0.62), Relationships (g = 0.55), and Digital media usage declined (g = 0.31), but not Reflections on life (g = -0.03). In cohort 3, the proportion of persons relying on their faith as a strong hold was declining also in nominally religious persons. Awe/Gratitude was among the best predictors of perceived positive changes, indicating a resource which is nevertheless declining during the second wave of the pandemic (g = 0.60). Conclusions: Several perceptions, attitudes, and behaviors have changed, particularly during the second wave of the pandemic, which had a strong influence on psychological health. Although Awe/Gratitude was confirmed as the best predictor of perceived positive changes, this resource may not buffer against the negative outcomes of the pandemic but helps to recognize the still positive aspects in life. There is a need for new and not yet defined public health communities that could focus on persons which are affected in their physical, mental, social, and spiritual health and well-being due to the pandemic.