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Customization model to examine the impact of more production lead time on inventory and distribution is presented.

The optimal purchasing policy for an N-period contract, and a more readily implementable heuristic policy is presented. By calculating the expecting profits of following such a policy, the user can conveniently choose between contracts with different commitments, constraints, and prices.

The goal of postmastectomy breast reconstruction (BR) is to improve the quality of life of patients. However, complications following autologous BR (A-BR) and implant-based BR (I-BR) occur frequently and may even lead to BR-failure, which can be a distressing event for both patients and surgeons. The current study, therefore, examines the experiences of both patients and surgeons after a BR-failure. Patients with a failed BR from a large multicenter cohort study and participating plastic surgeons were invited to participate in semi-structured interviews focusing on their experiences. The interviews were analyzed according to the principles of grounded theory. Fourteen patients with a failed I-BR, four patients with a failed A-BR, and four plastic surgeons were participated. Three main categories emerged from the data: personal experiences with BR-failure, the motives for a redo of a failed BR, and patient–surgeon communication. Patients would like to be treated with more attention to their personal feelings and lives, instead of being approached from a purely medical-technical perspective. Surgeons may experience feelings of guilt leading to the strong urge to fix the failed BR, whereas patients may be less inclined to undergo additional operations. Patients want to know what the choice for a particular type of BR would mean to their personal lives. The impact of I-BR-failure may be underestimated and requires the same degree of intensive aftercare and attention. Implementing the recommendations of this study in clinical practice may facilitate improvements in how both patients and surgeons cope with a BR-failure. [ABSTRACT FROM AUTHOR]

• First reported quantitative assay for the determination of galunisertib in human plasma. • Fast and elegant HPLC-MS/MS method for quantification of galunisertib in human plasma. • Application of a simple chromatographic method for quantification of galunisertib in small volumes of mouse plasma. Galunisertib is an anti-cancer drug currently evaluated in phase I and II clinical trials. This study describes the development and validation of a bioanalytical assay to quantify galunisertib in human plasma using HPLC-MS/MS. Stable isotope labelled galunisertib was added as internal standard and the analyte and internal standard were extracted from the matrix by protein precipitation using acetonitrile-methanol (50:50, v/v). Final extracts were injected onto a C18 column, gradient elution was applied for chromatographic separation and detection was performed using a triple quadrupole mass spectrometer operating in the positive ion mode. The assay was linear over the range 0.05–10 ng/mL, with acceptable accuracy (bias ranging from −6.1 to 3.1%) and precision (below 5.7% C.V.) values. The applicability of the assay was demonstrated in a pharmacokinetic experiment in mice. [ABSTRACT FROM AUTHOR]

Summary: Background: High satisfaction rates have been reported after autologous breast reconstruction. Yet, most mastectomy patients receive implant reconstructions (ImBR). Independent and active decision makers have shown mainly to choose for autologous reconstructions, such as the Deep inferior epigastric perforator (DIEP) flap (DiepBR). To further explore the decision making to opt for either ImBR or DiepBR, we investigated patient knowledge, informational resources used, effect of plastic surgeons’ advice, coping style and personal independence. Methods: A total of 153 women, who were planned for DiepBR or ImBR preoperatively, completed a study-specific and standardised validated psychological questionnaire. Analyses were aimed at information-seeking behaviour, personal independence and coping styles associated with autonomous decision making regarding reconstruction. Results: DiepBR women reported different informational resources to be very important and they were more active information seekers, compared with ImBR women. ImBR women found their physician’s advice to be more important in their decision making than DiepBR women. Actively seeking for information regarding BR was positively correlated with active coping, sensitivity to others and the decision for DIEP-flap BR. Conclusions: Women opting for DIEP-flap BR were more active and independent in their decision making regarding the type of BR. Women opting for implant BR seemed less well-informed and more dependent on their physician in their decision compared with women opting for DIEP-flap BR. To undergo a complex type of BR, active and independent information seeking may be required. However, clinical and logistic characteristics need to be considered, as some patients were limited in their reconstruction options. [ABSTRACT FROM AUTHOR]

Summary: Objective: Understanding women’s motives concerning breast reconstructive surgery will contribute to a better counselling and care for the increasing number of women choosing post-mastectomy breast reconstruction (BR). Methods: We interviewed 31 women who opted for implant or deep inferior epigastric perforator (DIEP)-flap BR after therapeutic or prophylactic mastectomy. Motives for BR in general and for the selected type of BR were investigated following a phenomenological qualitative research approach. Results: Women opting for implant BR were concerned with surgery-related issues, such as recovery time, number of scars and impact of surgery. They wanted to return to their daily life and restore their body image as soon as possible. Patients choosing DIEP-flap BR were more focussed on regaining a natural breast and wanted to benefit from the advantages of autologous tissue. Women scheduled for prophylactic mastectomy saw BR as an integral part of their treatment. Patients opting for BR after therapeutic mastectomy wanted to regain a complete body image with BR. Conclusions: Patients’ motives for implant BR were primarily related to surgical issues, whereas women who chose DIEP-flap BR especially focussed on regaining a breast that resembles their own lost breast as well as possible. Clinical variables (such as therapeutic or prophylactic mastectomy, breast irradiation, and waiting lists) need to be taken into account when considering a certain type of BR, as these can be of great importance in the decision-making process. [Copyright &y& Elsevier]

Summary: Background: Breast reconstruction (BR) is aimed at improving quality of life (QoL) after mastectomy. Patient satisfaction is an important indicator to evaluate the success of BR. This study explored patient satisfaction and its determinants in women undergoing deep inferior epigastric artery perforator (DIEP) flap BR as well as the impact of the procedure on body image, sexuality and QoL. Methods: Patient satisfaction and QoL were studied in 72 women who underwent DIEP flap BR using a study-specific questionnaire as well as the Short Form-36 (SF-36). Results: Patient satisfaction was very high. Approximately 90% of the patients reported that they had been sufficiently informed about the procedure and its consequences, that their preoperative expectations had been met, that the reconstructed breast felt like their own and that they would choose the same procedure again and would recommend this procedure to a friend. Patient satisfaction was positively and significantly related to the reconstructed breast(s) feeling like their own. Women with secondary reconstructions were more positive about changes in sexuality and femininity than women with primary BRs. There were no clinically relevant differences in QoL between our study population and a random sample of Dutch females. Conclusions: Women with DIEP flap BRs reported high satisfaction rates. However, to compare these satisfaction rates with other forms of BR, prospective studies in comparable groups are necessary. [Copyright &y& Elsevier]

Abstract: Huntington''s disease is characterised by a complex set of motor, neuropsychologic and psychiatric symptoms which start slowly and progress over many years to a state of complete dependency. The symptomatic treatment during the ambulatory years is divers. In the northern part of the Netherlands coordinated multidisciplinary care is offered to patients diagnosed with Huntington''s disease. A team of a neurologist, psychologist, occupational therapist, speech and language therapist, social worker and nursing home doctor monitors the patient and companion on a half-year basis and provide them with a plan of care. A case manager coordinates the plan of care in the dwelling place of the patient. In this article this type of care is outlined and illustrated with case histories. [Copyright &y& Elsevier]

Abstract: Worldwide, predictive testing for Huntington''s disease has become an accepted clinical application that has allowed many individuals from HD-families to proceed with their life without the uncertainty of being at risk. International guidelines have extensively contributed to establishing counselling programmes of high quality, and have served as a model for other genetic disorders. Psychological follow-up studies have increased the insight into the far-reaching impact of test results for all individuals involved. Although the guidelines have served as a useful frame of reference, clinical experience has shown the importance of a case-by-case approach to do justice to the specific needs of the individual test candidate. Issues such as ambiguous test results, lack of awareness in a test candidate of early signs of the disease, non-compliance to the test protocol, or the test candidate''s need for information on the relationship between age at onset and CAG-repeat require careful consideration. Receiving a test result is only one of the transition points in the life of an individual at risk; such result needs to be valued from a life-cycle perspective. [Copyright &y& Elsevier]

• Simultaneous quantification of abemaciclib and its active metabolites by UHPLC–MS/MS. • This method is selective, linear, accurate and precise. • This method is suitable for the analysis of mouse and human plasma samples. • Isomers of M20 and M18 were detected in mouse plasma. • M20 isomers were confirmed by HR-MS measurements. Abemaciclib is the third cyclin-dependent kinase 4 and 6 inhibitor approved for the treatment of advanced or metastatic breast cancer. In humans, abemaciclib is extensively metabolized by CYP3A4 with the formation of three active metabolites: N -desethylabemaciclib (M2), hydroxyabemaciclib (M20) and hydroxy- N -desethylabemaciclib (M18). These metabolites showed similar potency compared to the parent drug and were significantly abundant in plasma circulation. Thus, M2, M20, and M18 may contribute to the clinical activity of abemaciclib. For this reason, an UHPLC–MS/MS method for the simultaneous quantification of abemaciclib and its active metabolites in human and mouse plasma was developed and validated to support further clinical or preclinical investigations on this drug. Samples were processed by protein precipitation with acetonitrile, followed by supernatant dilution and filtration. Chromatographic separation was performed on a Kinetex C 18 column (150 × 2.1 mm ID, 2.6 μm) using gradient elution with 10 mM ammonium bicarbonate in water (eluent A) and in methanol-water (9:1, v/v, eluent B). This method was selective, linear, accurate and precise within the range of 1−600 ng/mL for abemaciclib, 0.5−300 ng/mL for M2 and M20, and 0.2−120 ng/mL for M18. Furthermore, stability of the analytes in human and mouse plasma samples in several conditions was demonstrated. Finally, this assay was successfully used in a preclinical pharmacokinetic study, where abemaciclib and its active metabolites were identified and quantified. Inter-species differences between human and mouse samples were encountered, especially in the formation of M20, where isomers of this compound were detected in mouse plasma, but not in human plasma. This was confirmed by high resolution-mass spectrometry (HR-MS) measurements. [ABSTRACT FROM AUTHOR]

Background and Objectives: We described a new treatment model for Posttraumatic Stress Disorder (PTSD) and Dissociative Identity Disorder (DID), based on cognitive-behavioural principles. In this model, dissociation is seen as a maladaptive avoidant coping strategy. In addition, we stress that patients have dysfunctional beliefs about dissociation. Both elements, avoidance behaviour and dysfunctional beliefs, are challenged during the brief, intensive trauma-focused treatment. When the PTSD-symptoms decrease, the patient is offered a fare-well ritual to say goodbye to their identities in one or more additional sessions.Methods: We illustrate this treatment approach with a case report of a woman with PTSD as a result of sexual abuse in her childhood, and DID with four identities. Treatment outcome was measured at intake, at pre-treatment, at post-treatment and at 3 and 6 months follow-up.Results: After the short treatment of only 2 weeks, she no longer fulfilled the DSM-5 diagnostic criteria for PTSD nor DID. These results were maintained at the follow-ups.Limitations: Although we included a baseline-controlled time phase, it was not a controlled study, and only one patient was treated.Conclusions: This new treatment model for DID-patients is promising but results should be interpreted cautiously since we described only one patient. [ABSTRACT FROM AUTHOR]

• Electronic health records (EHR) support health centre programs for HIV/AIDS. • Differences in documentation between EHR and paper records increase workload. • There are challenges to consistently operating and managing the EHR system. • The EHR system cannot communicate with other health or government facilities. • EHR use should be integrated with all health structures and processes. To investigate barriers to the effective use of electronic health records (EHR) to improve health outcomes for HIV/AIDS care treatment in health centres in rural areas of Botswana. In a qualitative study interviews were held with 57 staff members at 32 health centres in rural and remote areas of the country. Closed and open-ended questions were used to gain insights into the implementation and use of the EHR system. Transcripts were analysed and evaluated using thematic coding and structured around themes through NVivo 11 data analysis software. Themes covered were: changes in nursing practice; EHR system support; non-use of EHR; lack of leadership commitment to EHR use; and risks of using EHR. A large majority of staff were confident users of the EHR, despite limited training. Many nursing staff reported changes in administrative duties as documentation with EHR was different from that used in paper-based records and reports to management. Lack of appropriate support led to challenges in consistent operation and management of the EHR system. There were risks of data corruption through equipment failures and security vulnerabilities. The EHR system could not communicate with outside healthcare providers or facilities, leading to loss of patient follow up and delays in obtaining results of laboratory tests. Progress has been made with a national EHR system to support HIV management in Botswana within small local facilities. However, nurses' perspectives indicate limitations in staff training, insufficient support for health centres, and lost communication between facilities. Such barriers led to continued delays in treatment and fragmentation of health records. These areas should be addressed in further development. [ABSTRACT FROM AUTHOR]

• The first described bioanalytical assay for milciclib. • This method is suitable for the quantification of milciclib in several biomatrices. • A full validation in human plasma is described. • An application of a pharmacokinetic study of milciclib in mice is included. Milciclib is a promising cyclin-dependent kinase inhibitor currently in phase II clinical trials to treat several types of cancer. The first bioanalytical method for the quantitative analysis of milciclib in several biomatrices using liquid chromatography-tandem mass spectrometry is described here. This method was fully validated in human plasma according to FDA and EMA guidelines, and partially validated in mouse plasma, homogenates of mouse brain, kidney, liver, small intestine, spleen, and tissue culture medium. Palbociclib, an analog compound, was used as internal standard. A simple and fast sample pre-treatment by protein precipitation with acetonitrile was used, leading to efficient extraction of the analyte with recoveries between 95–100%. Chromatographic separation was achieved with a C 18 analytical column and a gradient elution using 10 mM ammonium bicarbonate in water and 10 mM ammonium bicarbonate in water-methanol (1:9, v/v). This assay was selective, accurate, precise and linear in the concentration range of 1−1000 ng/mL. Moreover, samples above the upper limit of quantification can be integrally diluted up to 10-fold prior to analysis. The use of human plasma as a surrogate matrix to quantify milciclib in tissue culture medium and mouse matrices resulted in acceptable accuracy and precision, however tissue culture medium samples required a dilution with human plasma prior the pre-treatment. All performance parameters of the method complied with the acceptance criteria recommended by the guidelines, except for the carry-over, which was slightly above (22.9% of the lower limit of quantification) the recommended percentage (20%). Therefore, additional measures were taken to assure data integrity. Stability of milciclib in all matrices was evaluated, and in some matrices the analyte was unstable under the tested conditions. It is therefore recommended to keep these samples as briefly as possible at room temperature during the pre-treatment, and to store them at –70 °C to avoid analyte degradation. This method was successfully applied to support preclinical pharmacokinetic studies of milciclib. [ABSTRACT FROM AUTHOR]

Objective This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Methods Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Results Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit–risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. Conclusions The majority of parents described undertaking benefit–risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. [ABSTRACT FROM AUTHOR]

Abstract: Individuals at risk for developing hereditary cancer are offered surveillance in order to improve the prognosis. An important question is whether the benefit of surveillance outweighs the psychological burden. In this review, we evaluated all studies that investigated psychological distress and the quality of life in individuals under surveillance for hereditary cancer of the breast, ovarian, prostate, pancreas, colorectum, melanoma, and various rare syndromes such as familial adenomatous polyposis, Li–Fraumeni and Peutz–Jeghers syndrome. Thirty-two studies were identified. Surveillance for most hereditary cancers was associated with good psychological outcomes. However, surveillance of individuals at high risk for developing multiple tumors appeared to be associated with increased distress and a lower quality of life. Common factors associated with worse psychological outcomes included a personal history of cancer, female gender, having a first degree relative with cancer, negative illness perceptions and coping style. The use of a simple screening tool to identify distressed individuals is recommended. [Copyright &y& Elsevier]

Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. This article describes the development and validation of a liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay to quantify lurbinectedin in human plasma and urine. Plasma samples were pre-treated with 1 M aqueous ammonia after which they were brought onto supported liquid extraction (SLE) columns. Lurbinectedin was eluted from the columns using tert -butyl methyl ether (TBME). Urine was first diluted in plasma and lurbinectedin was extracted from this matrix by liquid-liquid extraction using TBME. Samples were measured by LC–MS/MS in the positive electron ion spray mode. The method was linear over 0.1–100 ng/mL and 1–1000 ng/mL in plasma and urine, respectively, with accuracies and precisions within ±15% (20% for LLOQ) and below 15% (20% for LLOQ), respectively. The method was developed to support a mass balance study in which patients received a dose of 5 mg lurbinectedin. [ABSTRACT FROM AUTHOR]

Plitidepsin is an anti-cancer drug currently evaluated in phase I/II/III clinical trials. This article describes the development and validation of a bioanalytical assay to quantify plitidepsin in human plasma, urine and whole blood using HPLC–MS/MS. The analyte was extracted from the matrix by liquid–liquid extraction using tert -butyl methyl ether. Final extracts were injected onto a C18 column, gradient elution was applied for chromatographic separation and detection was performed on a triple quadrupole mass spectrometer operating in the positive ion mode. The assay was linear over the range 0.1–100 ng/mL, with acceptable accuracy and precision values. This is the first reported bioanalytical assay quantifying plitidepsin using a stable isotopically labelled standard, achieving a lower limit of quantification of 0.1 ng/mL in all three matrices, allowing the quantification of trace levels of plitidepsin, and accomplishing this in an analysis time of two minutes only. The presented method was successfully applied in a mass balance study with plitidepsin in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

We discuss the problem of proportionality and uniqueness for route flows in the classical traffic user equilibrium model. It is well-known that under appropriate assumptions the user equilibrium ( f , x ) is unique in the link flow x but typically not in the route flow f . We consider the concept of proportionality in detail and re-discuss the well-known relation between the so-called bypass proportionality and entropy maximization. We exhibit special proportionality conditions which uniquely determine the route flow f . The results are illustrated with some simple example networks. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Prophylactic mastectomy (PM) has proven to be the most effective method to reduce the risk of breast cancer in high-risk women. The present study aimed to present and compare the attitudes towards PM among physicians in France, Germany, the Netherlands and the United Kingdom (UK). Patients and methods: An international sample of 1196 general practitioners (GPs) and 927 breast surgeons (BS) were surveyed using a mailed questionnaire. Results: Only 30% of the French and 27% of the German GPs were of opinion that PM should be an option for an unaffected female BRCA1/2 mutation carrier, as compared to 85% and 92% of the GPs in the Netherlands and UK, respectively. Similarly, 78% of the French and 66% of the German BS reported a positive attitude towards PM, as compared to 100% and 97% of the BS in the Netherlands and UK, respectively. In the whole sample of GPs, a positive attitude towards PM was associated with country of residence, being female, and having more knowledge of breast/ovarian cancer genetics, while among BS there was a positive association with country of residence and having more knowledge of breast/ovarian cancer genetics as well, and, in addition, with a higher number of newly diagnosed breast cancer patients last year. Conclusion: These results demonstrated the international variations in the attitude towards PM among physicians. This might reflect that different policies are adopted to prevent breast cancer in women at-risk. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several melanoma susceptibility genes have been identified. As part of the international genetic research programme of the GenoMEL consortiums research on genetic mutations in melanoma families, the aim of this study was to examine family members’ views about their risk of melanoma, gene testing and genetic research. Methods: Self-report data were gathered using online and paper-based surveys available in four languages among 312 individuals (62% from Europe, 18% from Australia, 13% from the United States of America (USA) and 7% from Israel). Results: Fifty three percent had been diagnosed with a melanoma, and 12% had a positive susceptibility gene test result. Respondents with many moles and freckles were more likely to perceive themselves at risk for developing melanoma (odds ratio [OR]Freckles =2.24 with 95% confidence interval [CI]=1.18–4.26; ORMany moles =6.92, 95%CI=2.37–20.23). Respondents who had received a non-informative (negative) genetic test result were much less likely to perceive themselves at increased risk (OR=0.17, 95% CI=0.04–0.73). Safe-guards were perceived as important to protect genetic information, but there was also support for the storage and exchange of such information. Overall, respondents were in favour of genetic testing, even if current knowledge about melanoma risk genes is still limited. Contrary to previous studies, participants reported that a non-informative (negative) genetic test result, although not necessarily indicative of lower risk of melanoma, would be likely to reduce their practise of preventive behaviours. Conclusions: Participants were influenced by their phenotype and test results in risk estimations. They expressed positive views on genetic research and towards genetic testing, but reported that a non-informative (negative) test result might be associated with an (erroneous) perception of reduced risk and fewer preventive behaviours. These results highlight the urgency of improving the quality of genetic counselling and increasing the effectiveness of communication regarding genetic test results. [Copyright &y& Elsevier]

Abstract: Purpose: To explore the course of psychological distress and body image at long-term follow-up (6–9years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. Methods: Psychological distress (general and breast cancer specific) and body image (general and breast specific) were assessed in 36 high-risk women before PM (T0), at 6months (T1) and 6–9years (T2) after PM/BR. Investigated predictive variables (assessed at T0) for long-term body image (assessed at T2) included psychological distress, body image and coping styles. Results: Breast cancer specific and general distress significantly decreased from T0 to T1 as well as from T1 to T2. Problems regarding breast related and general body image were significantly higher at T1 than at T0. Subsequently, breast related body image scores significantly decreased from T1 to T2, while the decrease in general body image scores were not significant. Active coping and seeking social support were predictive of lower scores (i.e. less problems) on breast related and general body image at long-term follow-up. Furthermore, higher scores on general body image before PM/BR were predictive for increased general body image scores at long-term follow-up. Conclusion: Our findings indicate that psychological distress is decreased after PM/BR, at the cost of persistent problems regarding body image. Exploration of coping styles and body image perception before PM/BR may help to identify vulnerable women who may benefit from additional support. [Copyright &y& Elsevier]

OBJECTIVE: Previous studies suggest that learning a DNA-test-result has no direct impact on the medical-decisions and psychological well-being of counselees. Their perception, especially their recollections and interpretations of their cancer-risks and heredity, predict and/or mediate this impact. These studies were criticized for their small range of predictors, mediators, outcomes and contextual factors. We studied the short-term impact of DNA-testing with an extended model. METHODS: Three months after disclosure of BRCA1/2-test-results, we sent counselees a questionnaire about their perception, medical and psychological outcomes, and medical, familial and psychological contexts. 248 affected women participated; 30 had received pathogenic-mutations, 16 unclassified-variants and 202 uninformative-results. RESULTS: The actually communicated genetic-information and the contextual variables predicted the counselees' perception, but did not directly predict any outcomes. The counselees' perception predicted and/or completely mediated the counselees' medical intentions and behavior, physical and psychological life-changes, stigma, mastery, negativity and cancer-worries. Short-term distress was related to the perception not only of their own risks, but also of their relatives' risks and heredity-likelihood. Effect sizes were medium to large. CONCLUSIONS AND IMPLICATIONS: The outcomes of DNA-testing were better predicted by the counselees' perception than by the actually given genetic-information. We recommend genetic-counselors to have tailored, interactive dialogues about the counselees' perception. [ABSTRACT FROM AUTHOR]

Abstract: The levels and course of psychological distress before and after prophylactic mastectomy (PM) and/or prophylactic salpingo-oophorectomy (PSO) were studied in a group of 78 women. General distress was measured through the hospital anxiety and depression scale (HADS), cancer-related distress using the impact of events scale (IES). Measurement moments were baseline (2–4 weeks prior to prophylactic surgery), and 6 and 12 months post-surgery. After PM, anxiety and cancer-related distress were significantly reduced, whereas no significant changes in distress scores were observed after PSO. At one year after prophylactic surgery, a substantial amount of women remained at clinically relevant increased levels of cancer-related distress and anxiety. We conclude that most women can undergo PM and/or PSO without developing major emotional distress. More research is needed to further define the characteristics of the women who continue to have clinically relevant increased scores after surgery, in order to offer them additional counselling. [Copyright &y& Elsevier]

Abstract: This study explored predictors for hereditary cancer distress six months after genetic susceptibility testing for a known familial BRCA1/2 or HNPCC related mutation, in order to gain insight into aspects relevant for the identification of individuals needing additional psychosocial support. Coping, illness representations, experiences with cancer in relatives and family system characteristics were assessed in 271 applicants for genetic testing before result disclosure. Hereditary cancer distress was assessed prospectively up to six months after disclosure. Regression analysis revealed that the pretest level of distress, complicated grief, the number of affected first-degree relatives and strong emotional illness representations were factors that best explained hereditary cancer distress. Other significant predictors were illness coherence, passive coping, distraction seeking, being aged <13 years when a parent was affected by cancer and family communication. Individuals who may benefit from additional support may be identified before result disclosure using a short instrument assessing the relevant aspects. [Copyright &y& Elsevier]

Abstract: Objective: To study differences between individuals opting for genetic cancer susceptibility testing of a known familial BRCA1/2 and HNPCC related germline mutation. Methods: Coping, illness perceptions, experiences with cancer in relatives and family system characteristics were assessed in 271 applicants for genetic testing before test result disclosure. Hereditary cancer distress, worry and cancer risk perception were assessed before, 1 week after, and 6 months after disclosure. Results: Individuals from BRCA1/2 and HNPCC mutation families did not differ with regard to the number of experiences with cancer in relatives, grief symptoms, the course of cancer distress, worry and risk perception through time and most illness perceptions, coping responses and family characteristics. Individuals from BRCA1/2 families perceived hereditary cancer as more serious. They reported more frequently a passive coping style, cancer worry and a less open communication with their partner and children. Conclusion: Besides subtle differences, psychological mechanisms may be mainly identical in individuals opting for BRCA1/2 and HNPCC susceptibility testing. Practice implications: Based on our findings, using a similar counseling approach for individuals opting for BRCA1/2 or HNPCC genetic susceptibility testing is justified. In this approach, attention should be directed more to individual aspects than to the type of disorder. [Copyright &y& Elsevier]

Abstract: Objective: Based on the premise that attachment experiences lead to a working model for social relationships throughout life, this study investigates if there is a difference between adult attachment representations in individuals who were brought up by a parent with Huntington''s disease (HD), compared to a non-clinical population. Specific events in the parents’ disease process, especially those leading to trauma and loss will receive attention. Methods: Using the Adult Attachment Interview, adult attachment representations were investigated in 32 unaffected adults at 50% risk for HD who were raised by an affected parent. Results: We found a lower percentage of secure attachment representations, a higher percentage of preoccupied representations, and a higher percentage of unresolved/disorganized representations in our sample, compared to a non-clinical population. A relatively late start of the parent''s HD career was associated with a secure adult attachment representation. Death of the HD parent before the child''s 18th birthday was associated with an unresolved/disorganized adult attachment representation. Conclusion: Growing up in a family where one of the parents has Huntington''s disease appears to affect the offspring''s adult attachment representation. Practice implications: This study can be of relevance for genetic counselling, as well as for counselling and intervention in childrearing matters. [Copyright &y& Elsevier]

Abstract: In this article we determined the course of psychological distress during a breast cancer surveillance program in women at increased risk of developing hereditary breast cancer (BC). The sample comprised of 357 unaffected women (mean age 40.5 years) adhering to a surveillance programme (MRISC-study). Before and after two successive biannual surveillance appointments, the Impact of Event Scale (BC-specific distress) and the Hospital Anxiety and Depression Scale (general distress) were administered, totalling four measurement moments. In general, psychological distress remained within normal limits and decreased significantly after a surveillance appointment, except for breast cancer specific distress after the second appointment. Scheduled imaging examinations were not significantly related to distress. The course of BC specific distress differed significantly for risk over-estimators and for young (&#60;40 years) excessive breast self examiners. The course of general distress differed significantly for women closely involved in a sister’s BC-process. These more vulnerable subgroups may be in need of extra counselling and care. [Copyright &y& Elsevier]

The magnetic resonance imaging screening (MRISC) study evaluates a surveillance programme for women with a hereditary risk for breast cancer. The psychological burden of surveillance in these women may depend on inaccurate risk perceptions. To examine differences in risk perceptions between three predefined risk categories and associations with psychological distress. BC-specific distress, general distress, and RP (cognitive and affective) were assessed, two months before a surveillance appointment. Cumulative lifetime risk (CLTR) of developing breast cancer was trichotomised into: (1) CLTR of 60–85% (mutation carriers), (2) CLTR of 30–50%, and (3) CLTR of 15–30%. In a total group of 351 women (mean age 40.5 years, range 21–63 years) the three risk categories significantly differed in their accuracy of assessing cognitive risk perceptions. In category 1, 60% had an accurate risk perceptions, in category 2, 43.7% and in category 3, 33.3%. Overestimators reported significantly more breast cancer-specific distress. After adding affective risk perception to the model, this effect disappeared. Affective risk perceptions showed significant associations with breast cancer-specific and general distress. Affective risk perception is a more important determinant for psychological distress than cognitive risk perception. This knowledge should be used during surveillance appointments in order to improve and individualise support for these women. [Copyright &y& Elsevier]

Background: The present study aimed to assess predictors of distress after ’prophylactic mastectomy (PM) and salpingo-ovariectomy (PSO), in order to enable the early identification of patients who could benefit from psychological support. Patients and methods: General distress and cancer-related distress were assessed in 82 women at increased risk of hereditary breast and/or ovarian cancer undergoing PM and/or PSO, before and 6 and 12 months after prophylactic surgery. Neurotic lability and coping were assessed before surgery. Results: Cancer-related distress and general distress at both follow-up moments were best explained by the level of cancer-related and general distress at baseline. Being a mutation carrier was predictive of increased cancer-related distress at 6-month follow-up (but not at 12 months), and of lower general distress 12 months after prophylactic surgery. Also, coping by having comforting thoughts was predictive of less cancer-related distress at 6-month follow-up. Conclusions: Genetically predisposed women who are at risk of post-surgical distress can be identified using one or more of the predictors found in this study. Exploration of and/or attention to cancer-related distress and coping style before prophylactic surgery may help physicians and psychosocial workers to identify women who might benefit from additional post-surgical support. [ABSTRACT FROM AUTHOR]