Psychosocial well-being of long-term survivors of pediatric head-neck rhabdomyosarcoma.

BACKGROUND: Head and neck rhabdomyosarcoma (HNRMS) survivors are at risk to develop adverse events (AEs). The impact of these AEs on psychosocial well-being is unclear. We aimed to assess psychosocial well-being of HNRMS survivors and examine whether psychosocial outcomes were associated with burden of therapy. PROCEDURE: Sixty-five HNRMS survivors (median follow-up: 11.5 years), treated in the Netherlands and the United Kingdom between 1990 and 2010 and alive ≥2 years after treatment visited the outpatient multidisciplinary follow-up clinic once, in which AEs were scored based on a predefined list according to the Common Terminology Criteria for Adverse Events. Survivors were asked to complete questionnaires on health-related quality of life (HRQoL; PedsQL and YQOL-FD), self-perception (KIDSCREEN), and satisfaction with appearances (SWA). HRQoL and self-perception scores were compared with reference values, and the correlation between physician-assessed AEs and psychosocial well-being was assessed. RESULTS: HNRMS survivors showed significantly lower scores on PedsQL school/work domain (P ≤ 0.01, P = 0.02, respectively), YQOL-FD domains negative self-image and positive consequences (P ≤ 0.01, P = 0.04, respectively) compared with norm data; scores on negative consequences domain were significantly higher (P = 0.03). Over 50% of survivors negatively rated their appearances on three or more items. Burden of AEs was not associated with generic HRQoL and self-perception scores, but was associated with disease-specific QoL (YQOL-FD). CONCLUSION: In general, HRQoL in HNRMS survivors was comparable to reference groups; however, survivors did report disease-specific consequences. We therefore recommend including specific questionnaires related to difficulties with facial appearance in a systematic monitoring program to determine the necessity for tailored care.

EVIDENCE REQUIREMENTS FOR REIMBURSEMENT OF PHARMACEUTICALS ACROSS EUROPE.

OBJECTIVES: The objective of this study was to compare evidence requirements for health technology assessment of pharmaceuticals by national agencies across Europe responsible for reimbursement decisions focusing specifically on relative effectiveness assessment. METHODS: Evidence requirements from thirty-three European countries were requested and twenty-nine national agencies provided documents to review. Data were extracted from national documents (manufacturer's submission templates and associated guidance) into a purpose-made framework with categories covering information about the health condition, the technology, clinical effectiveness and safety. RESULTS: The level of detail in the required evidence varies considerably across countries. Some countries include specific questions while others request information under general headings. Some countries include all information in a single document, which may or may not include guidance on how to complete the template. Others have specific guidance documents or methods and process manuals that help with the completion of the submission templates. Despite differences in quantity and detail, the content of the evidence requirements is broadly similar. All countries ask for information on the health technology, target disease, and clinical effectiveness and safety. However, one country only requests clinical effectiveness information as part of cost-effectiveness analyses. We found twenty-six evidence requirements for which generic answers may apply across borders and nineteen in which countries requested nationally specific information. CONCLUSIONS: This work suggests that it would be possible to put together a minimum set of evidence requirements for HTA to support reimbursement decisions across Europe which could facilitate collaboration between jurisdictions.

Frequent occurrence of cytomegalovirus retinitis during immune reconstitution warrants regular ophthalmic screening in high-risk pediatric allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Although cytomegalovirus (CMV) retinitis (CMVR) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT), standard operating procedures for ophthalmic monitoring are variable. In particular, authors perceived a greater risk of CMVR after pediatric HSCT for inherited immunodeficiencies, in patients who often have pretransplantation viremia. This study was therefore performed to identify high-risk pediatric HSCT recipients who would benefit from regular ophthalmic monitoring. METHODS: During a 5-year study period, we retrospectively analyzed findings in 56 of 304 consecutive HSCT recipients (age range, 0.5-197 months) in whom significant CMV viremia developed (CMV level at PCR, ≥4000 copies/mL). All HSCT recipients with significant CMV viremia underwent retinal examination weekly (inpatients) or every other week (outpatients), with examinations performed by a skilled ophthalmologist. RESULTS: CMVR developed in 13 (4%) of 304 HSCT recipients, 23% (13 of 56) of those with significant CMV viremia. Pretransplant viremia (odds ratio, 11.3; P < .01), acute (grade ≥2) graft-vs-host disease (odds ratio, 8.2; P < .02) and mismatched graft (odds ratio, 8; P < .02) were identified as independent risk factors. Compared with other invasive CMV diseases, CMVR was more often a late-onset disease, occurring at a median of 199 days after HSCT. At diagnosis, a significantly higher CD4 T-cell count (≥200/µL; P < .03) and a lower CMV load (P < .004) was observed in children with CMVR, compared with those in whom lung, gut, or liver CMV disease developed. CONCLUSIONS: We report an increased risk of CMVR in high-risk pediatric HSCT recipients. This form of CMV disease differs from other invasive CMV disease in its relationship to immune reconstitution and viral dynamics. We have studied the relationship between these variables and suggested a risk-stratified ophthalmic screening strategy.

A multinational study exploring adolescent perception of school climate and mental health.

School climate is a topic of increasing importance internationally. The current study investigated the established measurement invariance of an eight-factor school climate scale using a multinational sample of secondary students. School climate factor means across 14 international groups were compared and findings on the association between school climate factors and mental health were also investigated. Findings, from this study, illustrate several cross-national similarities regarding the ways in which secondary students perceive school climate and the influence of school climate on student mental health. These findings can support school psychologists' efforts to identify strategies and supports that improve the school environment in areas that are most consistently related to student experiences, such as school safety and school connectedness. Implications, limitations, and future directions are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Case series: Pyramidal cataracts, intact irides and nystagmus from three novel PAX6 mutations.

PURPOSE: To investigate the association between novel PAX6 mutations to bilateral anterior pyramidal congenital cataracts (APyC), complete and intact irides, and nystagmus. OBSERVATIONS: This is a retrospective observational case series in a multi-center setting with genetic testing. Three female patients were diagnosed with bilateral APyC, intact irides and nystagmus. Genetic testing identified the three patients had novel missense mutations in PAX6 - c.128C > T; p.Ser43Phe (S43F), c. 197T > A; p.Ile66Asn (I66N) and c.781C > G; p.Arg261Gly (R261G). CONCLUSIONS AND IMPORTANCE: This study demonstrates a novel phenotype of bilateral APyC, intact irides, and nystagmus in whom genetic testing for PAX6 identified novel missense mutations (S43F, I66N, R261G) in highly conserved DNA-binding domains. Implications of understanding why the iris is present in these cases is discussed.

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment.

BACKGROUND: Radiotherapy is a well-known cause of adverse events (AEs). To reduce AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery, MOuld brachytherapy and surgical REconstruction (AMORE). AIMS: (1) to determine the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors treated with the international standard: external beam radiotherapy (EBRT-based: London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE-based: Amsterdam). METHODS: All HNRMS survivors, treated in London or Amsterdam between January 1990 and December 2010 (n = 153), and alive ⩾ 2 years post-treatment were eligible (n = 113). A predefined list of AEs was assessed in a multidisciplinary clinic and graded according to the Common Terminology Criteria for Adverse Events. RESULTS: Eighty HNRMS survivors attended the clinic (median follow-up 10.5 years); 63% experienced ⩾ 1 severe or disabling event, and 76% had ⩾ 5 AEs (any grade). Survivors with EBRT-based treatment were, after adjustment for site, age at diagnosis, and follow-up duration, at increased risk to develop any grade 3/4 event or ⩾ 5 AEs (any grade) compared with survivors with AMORE-based treatments (p = 0.032 and 0.01, respectively). Five year overall survival (source population) after EBRT-based treatment was 75.0%, after AMORE-based treatment 76.9%, p = 0.56. CONCLUSION: This study may serve as a baseline inventory and can be used in future studies for prospective assessments of AEs following the introduction of novel local treatment modalities. AMORE-based local treatment resulted in similar overall survival and a reduction of AEs secondary to local treatment.

Caterpillar setae penetration in an eye: long-term follow-up.

PURPOSE: To report the results of 9 years of follow-up after caterpillar setae penetration into a child's eye. METHODS: The clinical course of caterpillar setae penetrating an eye and their migration will be described. Initially confined to the anterior segment (conjunctiva, cornea), they later migrated to the anterior chamber and iris toward the posterior pole. Management included treatment of the associated recurrent uveitis and repeated surgical interventions including pars plana vitrectomy. PATIENTS: Ten-year-old boy at the time of the initial eye injury. RESULTS: It was not possible to completely remove the caterpillar setae that had penetrated the conjunctiva and cornea. Later attempts to remove the setae from the anterior chamber and the vitreous by pars plana vitrectomy were also unsuccessful. Argon laser photocoagulation was performed around the setae, which later reached the retina, but did not prevent their further migration. CONCLUSION: Management of an eye injury caused by caterpillar setae is problematic because they are almost impossible to remove from eye tissue. Setae have a tendency to migrate in the eye. It requires long-term follow-up, conservative management of recurrent uveitis, as well as repeated surgical interventions.