ESMO Recommendations on clinical reporting of genomic test results for solid cancers.

BACKGROUND: Genomic tumour profiling has a crucial role in the management of patients with solid cancers, as it helps selecting and prioritising therapeutic interventions based on prognostic and predictive biomarkers, as well as identifying markers of hereditary cancers. Harmonised approaches to interpret the results of genomic testing are needed to support physicians in their decision making, prevent inequalities in precision medicine and maximise patient benefit from available cancer management options. METHODS: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group assembled a group of international experts to propose recommendations for preparing clinical genomic reports for solid cancers. These recommendations aim to foster best practices in integrating genomic testing within clinical settings. After review of available evidence, several rounds of surveys and focused discussions were conducted to reach consensus on the recommendation statements. Only consensus recommendations were reported. Recommendation statements were graded in two tiers based on their clinical importance: level A (required to maintain common standards in reporting) and level B (optional but necessary to achieve ideal practice). RESULTS: Genomics reports should present key information in a front page(s) followed by supplementary information in one or more appendices. Reports should be structured into sections: (i) patient and sample details; (ii) assay and data analysis characteristics; (iii) sample-specific assay performance and quality control; (iv) genomic alterations and their functional annotation; (v) clinical actionability assessment and matching to potential therapy indications; and (vi) summary of the main findings. Specific recommendations to prepare each of these sections are made. CONCLUSIONS: We present a set of recommendations aimed at structuring genomics reports to enhance physician comprehension of genomic profiling results for solid cancers. Communication between ordering physicians and professionals reporting genomic data is key to minimise uncertainties and to optimise the impact of genomic tests in patient care.

Mothers of twins had higher old-age survival than mothers of singletons in Estonian 19th-century birth cohorts.

STUDY QUESTION: Do the mothers of twins and singletons differ regarding post-partum and old-age mortality? SUMMARY ANSWER: Twin deliveries were associated with higher post-partum maternal mortality than singleton deliveries, but the lifetime post-partum mortality risk was similar for mothers of twins and singletons; survival of twinners was higher than survival of the mothers of singletons after the 67th lifespan percentile. WHAT IS KNOWN ALREADY: Twinning is typically associated with higher post-partum maternal mortality. The evidence about whether twinning incurs long-term survival costs of reproduction or is a trait pertinent to long-lived women is scarce and contradictory. STUDY DESIGN, SIZE, DURATION: The study is based on the data of the Estonian Family Register (operating from 1926 to 1943) and involves 5565 mothers of twins and 119 613 mothers of singletons born between 1850 and 1899. The subset for comparing maternal lifespans included 1703-1884 mothers of twins and 19 747-36 690 mothers of singletons. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-partum maternal mortality was analyzed in the whole sample (including mothers of a single child) by logistic regression. Most of the analyses were performed in samples where each mother of twins was matched against mothers of singletons based on parity (or number of deliveries), urban versus rural and inland versus coastal origin, whether their lifespan was known, date of birth and age at first birth. Lifespans were compared in linear mixed models. Quantile regression was used to analyze age-dependent variations in maternal mortality rates. All models were adjusted for relevant biodemographic covariates. MAIN RESULTS AND THE ROLE OF CHANCE: The twinning rate in the whole sample was 4.4%. During the year after giving birth, maternal mortality for twin deliveries was 0.75% (17/2273) and 0.37% (449/122 750) for singleton deliveries (OR = 2.05, 95% CI = 1.21-3.23). However, the lifetime post-partum mortality risk for mothers of twins (0.51%; 28/5557) and singletons (0.37%; 438/119 466) did not differ significantly (OR = 1.38, 95% CI = 0.91-1.98). The life spans of the mothers of twins and singletons did not differ in matched samples. Past the 67th lifespan percentile, the odds of survival were significantly higher for mothers of twins than mothers of singletons, as indicated by non-overlapping 95% confidence intervals. LIMITATIONS, REASONS FOR CAUTION: Relatively low number of individuals (22 802-28 335) with known age at death in matched datasets due to discontinuation of the register after 1943. WIDER IMPLICATIONS OF THE FINDINGS: The finding that mothers of twins had higher odds of old-age survival than mothers of singletons is consistent with the contention that twinners represent a non-random subset of women whose robust phenotypic quality allows them to outlive the mothers of singletons in old age. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Estonian Research Council grants PRG1137, PRG2248, and PSG669. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Drug survival analysis of etanercept compared with monoclonal antibody tumour necrosis factor-α inhibitors in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a propensity score-matched analysis from the Czech ATTRA registry.

OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

Mode mixing and losses in misaligned microcavities.

We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.

Pneumoperitoneum, pneumomediastinum and subcutaneous emphysema following argon plasma coagulation treatment of colonic angioectasia.

INTRODUCTION: The paper presents unusual symptoms as a complication of therapeutic colonoscopy. CASE REPORT: A 70-year-old polymorbid female patient in chronic dialysis program underwent argon plasma coagulation treatment of leaking angioectasias in the cecum and ascending colon. Shortly after the procedure she presented with shortness of breath and subcutaneous emphysema of the neck which was initially misdiagnosed as swelling. Further tests revealed pneumoperitoneum, subcutaneous emphysema and pneumomediastinum. Considering the high risks for our patient (comorbidities, obesity), a laparoscopic approach was indicated. During laparoscopy neither peritonitis nor intestinal perforation were found. The patient recovered without complications after further complex treatment. CONCLUSION: Shortness of breath and subcutaneous emphysema are not typically among the first symptoms of colonoscopic perforation. Our case confirms that we should bear this complication in mind and when suspected, the diagnostic process should be started without delay.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

High tumour mutational burden and EGFR/MAPK pathway activation are therapeutic targets in metastatic porocarcinoma.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. OBJECTIVES: To investigate the drivers of EPC progression. METHODS: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient-derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. RESULTS: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer-relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen-activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient-derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR-directed therapy and immune checkpoint inhibition for more than 2 years. CONCLUSIONS: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC.

Avian schistosome species in Danish freshwater lakes: relation to biotic and abiotic factors.

Due to the increased prevalence of human infections with bird schistosome larvae (cercarial dermatitis) associated with bathing in Danish lakes, a nationwide survey of infected intermediate host snails was conducted in 2018-2020. Pulmonate snails (10,225 specimens) were collected from 39 freshwater lakes (in the four major geographic regions in Denmark) and subjected to shedding. Released schistosome cercariae were isolated and identified by polymerase chain reaction and sequencing whereby Trichobilharzia regenti, Trichobilharzia franki, Trichobilharzia szidati and Trichobilharzia anseri were recorded. Infections were primarily determined by biotic factors such as the presence of final host birds and intermediate host snails and water temperature was noted as an important abiotic parameter associated with the infection. No clear connection with other abiotic factors (conductivity, alkalinity, pH, nitrogen, phosphorous) was seen. The widespread occurrence of infected snails, when compared to previous investigations, suggests that climate changes at northern latitudes could be responsible for the increased risk of contracting cercarial dermatitis.

Bronchogenic cyst of gastric cardia - case report and literature review.

INTRODUCTION: Intramural bronchogenic cysts of the esophagus are very rare. They are mostly found in the upper mediastinum. Symptoms are caused by compression of surrounding structures by the cyst or complications of the cyst. However, the majority are asymptomatic. CASE REPORT: We describe the case of a 30-year-old female patient who underwent surgery at our institution for a tumor of the gastric cardia protruding intraluminally. The tumor was found incidentally during upper endoscopy before a planned bariatric surgery. A solid lesion originating from the muscle layer of the cardia wall was described based on endoscopic ultrasound. A CT scan did not show any infiltration of surrounding structures or disease dissemination. We performed laparoscopic enucleation of the tumor combined with partial fundoplication to close the defect in the muscular layer of the esophagus. Histopathology report surprisingly confirmed a bronchogenic cyst in the gastric cardia wall. The patient healed primarily and was soon discharged without complications. Two months later she underwent sleeve gastrectomy for obesity. Seven months following the bronchogenic cyst enucleation an endoscopic balloon dilation was performed on the patient with good effect upon diagnosing a relative gastric cardia stenosis. CONCLUSION: The diagnosis of esophageal bronchogenic cysts is usually difficult. Histopathology results are crucial to determine the definitive diagnosis. Endoscopy and imaging techniques, including endoscopic ultrasound, play an important role in the diagnostic process. Most authors prefer complete removal of the cyst, endoscopic or surgical, due to possible cyst complications, diagnostic uncertainty, and certainly in symptomatic patients. The complication rate is minimal.

Is high age a contraindication to pulmonary resection?

INTRODUCTION: As the population ages, there are increasing numbers of elderly patients diagnosed with operable primary pulmonary malignancy or other lesions requiring pulmonary resection. The objective of the study was to evaluate post-operative outcomes in the elderly group and compare them with younger patients undergoing the same surgery. METHODS: Retrospectively, we evaluated our own set of 424 patients undergoing anatomical pulmonary resection for primary lung cancers and other resectable lesions in 20112020. 328 patients underwent open procedures, and VATS lobectomy was performed 96 times. We evaluated the set of patients in terms of 30-day morbidity and mortality using Clavien-Dindo classification modified for pulmonary resections. We compared the patient subgroups by age (under 55, 5564 years old, 6574 years and over 75 years). RESULTS: A non-biometric Kruskal-Wallis test was used to compare the groups. We have not shown a statistically significant difference in the number of complications (p=0.220). CONCLUSION: Standard surgical treatment for non-small cell lung carcinoma, lobectomy with systematic mediastinal lymphadenectomy, is safe also for a well-indicated group of seniors. With careful preoperative assessments and consideration of the extent of resection, we can expect a comparable rate of complications in the elderly compared to younger patients. Sublobar resection or radiotherapy should be considered in case of patients at risk. For seniors over 70 years of age, comparable outcomes of oncological treatment can be reached, taking into account their shorter life expectancy.

Delirious conditions in surgical ICU - case report.

Delirious conditions are encountered in daily practice in the surgical ward, especially in intensive care units (ICUs). An ordinary surgeon must deal with these conditions very often. The case report of a patient with alcoholic delirium is presented. For a comprehensive view of the issue, we present a simple communication on delirious situations in the ICU. Deliria are classified according to their manifestations, and their etiology is briefly described. For practice, an outline of examinations and treatments is provided which is fundamentally different for alcoholic and nonalcoholic delirium.

Postpneumonectomy MRSA empyema treated with vacuum therapy - case report and literature review.

INTRODUCTION: Postpneumonectomy empyema is one of serious complications with high mortality and lethality. In this paper, the authors describe the treatment of methicillin-resistant Staphylococcus aureus-induced postpneumonectomy empyema by vacuum therapy in a patient operated on for malignant pleural mesothelioma. CASE REPORT: A 64-year-old patient was operated on at our clinic for epithelioid mesothelioma of the right pleural cavity. We performed extrapleural pneumonectomy with intraoperative hyperthermic intrathoracic chemotherapy. Seven weeks after surgery the patient was readmitted for right pleural cavity empyema caused by methicillin-resistant Staphylococcus aureus (MRSA). Following pleural cavity debridement and mesh explantation we applied vacuum therapy. In total, we performed 4 dressing changes with final application of an antibiotic solution into the pleural cavity and wound closure. The patient showed no evidence of recurrent empyema during subsequent 12-month follow-up and underwent chemotherapy. CONCLUSION: Vacuum therapy is an effective treatment of postpneumonectomy empyema in patients without a bronchopleural fistula; nevertheless, specific postpneumonectomy patient care is required.

Pulmonary metastases in pseudomyxoma peritonei - case report and review of the literature.

Pseudomyxoma peritonei is a rare disease caused by dissemination of cancer forming mucous and gelatinous masses in the peritoneal cavity. Local recurrence is frequent; however, dissemination outside the peritoneal cavity is rare.  Case report: We present the case report of a female patient treated for bilateral pulmonary metastases from pseudomyxoma peritonei. We removed 1 metastasis from her left lung and 12 metastases form her right lung. The patient remained in a good clinical state; however, additional lung metastases developed, as well as a metastasis in L2 vertebra for which the patient underwent a surgical procedure. Conclusion: Cytoreductive surgeries for intrathoracic involvement in pseudomyxoma peritonei with additional hyperthermic cytostatic intrapleural lavage in case of pleural involvement can lead to a longer lifespan in indicated patients.

The most recent recommendations for the surgical treatment of inguinal hernia.

INTRODUCTION: The publication of new guidelines in recent years shows that surgical treatment of inguinal hernia remains topical. The main goal is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain. The main purpose of this article is to summarize the latest recommendations in surgical treatment of the groin hernias, especially in the case of strangulation. METHODS: The authors made literature review of all the guidelines published by the hernia societies, including related articles, in the last ten years. RESULTS: The use of the EHS classification system is suggested. In elective operations, mesh repair is recommended. The Lichtenstein technique is the standard in open inguinal hernia repair. Transabdominal preperitoneal and totally extraperitoneal approach have comparable outcomes. Their clear advantages include minimal invasiveness. Mesh repair is recommended also in the case of strangulation, but only in clean and clean-contami-nated operations. A laparoscopic approach should be considered as well. Inter alia, it allows an assessment of bowel viability during the whole procedure. The need of bowel resection is hence lower compared to open surgery. If it is not possible to use the mesh, the Shouldice method is regarded as the best non-mesh repair technique. If there is concern about bowel viability, visualization, either by formal laparoscopy, hernia sac laparoscopy or laparotomy, is recommended. Hernioscopy is a simple and safe procedure that uses the hernia sac for insertion of a port following insufflation and diagnostic examination. It requires less advanced laparoscopic skills than does emergency laparoscopic hernia repair. It can be performed even by surgeons who lack sufficient experience with laparoscopy. CONCLUSION: In elective procedures, the mesh repair is recommended. It is recommended also in the case of strangulation, but not in a contaminated-dirty surgical field. If there is concern about bowel viability, visualization, either by formal laparoscopy, hernia sac laparoscopy or laparotomy, is needed.

Splenic abscess as a rare symptom of the extrapulmonary tuberculosis - case report.

INTRODUCTION: Extrapulmonary tuberculosis can involve any organ or tissue. It is a rare disease in the Czech Republic with an incidence rate of 0.62 cases per 100.000 persons. It affects mostly immunocompromised patients. The most common sites include lymph nodes, the urogenital system, skin, joints, bones and serous epithelium - the peritoneum, pleura, and pericardium. Splenic involvement is rare. Mycobacterium is a slow growing intracellular parasite. The diagnostic process is very difficult; microbiological diagnosis is critical. CASE REPORT: An 84 years old female patient with subcapsular splenic rupture with no trauma history as a cause of anemia. Splenic abscess was diagnosed during surgical revision and splenectomy. Tuberculosis was suspected based on subsequent histological analysis, which was confirmed after nine weeks of peritoneal fluid culture. The surgical procedure and postoperative hospitalization were not associated with any complications. The patient was referred to the respiratory clinic for further treatment. CONCLUSION: The diagnosis of extrapulmonary tuberculosis including splenic localization should always be considered. A sample from the affected tissue or effusion must be collected in the case of unclear perioperative findings and sent for complete bacteriological testing, including mycobacterial culture. If a tuberculous splenic abscess is found, the therapeutic process should involve its complete drainage in combination with long-term anti-TB medication.

[Personalized oncology]. / Personalisierte Onkologie.

CLINICAL ISSUE: Innovative next generation sequencing (NGS) technologies and comprehensive sequencing investigations in large patient cohorts have paved the way for very promising personalized treatment strategies based on the molecular characteristics of individual tumors. STANDARD TREATMENT: Targeted therapies, such as tyrosine kinase inhibitors, antibodies and modern immunotherapeutic approaches are well established as monotherapy and combination therapy for many hematological and oncological malignancies. TREATMENT INNOVATIONS: A plethora of innovative therapies targeting various components of intracellular signaling cascades and effective mechanisms against oncogenes as well as the availability of NGS technologies enable personalized cancer treatment based on the molecular profiles of individual tumors and genetic stratification, within clinical trials. DIAGNOSTIC WORK-UP: Comprehensive genetic approaches including cancer gene panel sequencing, whole exome, whole genome and transcriptome sequencing are carried out to a varying extent and particularly in the academic setting. PERFORMANCE: Principally, a comprehensive characterization of tumors in addition to DNA and RNA sequencing that also incorporates epigenetic, metabolomic, and proteomic alterations would be desirable. A comprehensive clinical implementation of integrative, multidimensional genetic typing is, however, currently not possible. ACHIEVEMENTS: It remains to be demonstrated whether these approaches will translate into significantly better outcomes for patients and whether they can be increasingly implemented in the routine diagnostic work-up. PRACTICAL RECOMMENDATIONS: The selection of diagnostic tools in individual cases and the extent of genomic analyses in the clinical context, need to take the availability of methods as well as the present clinical situation into account.

Inter-modal four-wave mixing study in a two-mode fiber.

We demonstrate efficient four-wave mixing among different spatial modes in a 1-km long two-mode fiber at telecommunication wavelengths. Two pumps excite the LP01 and LP11 modes, respectively, while the probe signal excites the LP01 mode, and the phase conjugation (PC) and Bragg scattering (BS) idlers are generated in the LP11 mode. For these processes we experimentally characterize their phase matching efficiency and bandwidth and find that they depend critically on the wavelength separation of the two pumps, in good agreement with the numerical study we carried out. We also confirm experimentally that BS has a larger bandwidth than PC for the optimum choice of the pump wavelength separation.

[Double incision laparoscopic surgery]. / Laparoskopická chirurgie ze dvou incizí.

INTRODUCTION: Single incision laparoscopic surgery (SILS) is a common alternative to classical laparoscopic surgery. However, material costs of SILS significantly limit the spreading of this method to most of surgical departments in the Czech Republic. Therefore we introduced DILS, which is technically more difficult than 3- to 4-incision laparoscopy but comparable cost-wise and its result approaches the cosmetic effect of SILS. METHODS: We describe the technical approach for DILS. We evaluate our own group of patients who were operated on in 2012-2014. RESULTS: Nine minor complications evaluated as Clavien-Dindo grade I-IIIb were seen in the group of 64 patients undergoing laparoscopic cholecystectomy, appendectomy or TAPP operation of groin hernias using DILS method. DILS-cholecystectomy was converted to multiple-ports laparoscopy 4 times. CONCLUSION: In our group, DILS did not present a higher complication rate than laparoscopic surgery using multiple incisions. This method is well-regarded by the patients in terms of its aesthetic results, and economically it is more advantageous than SILS. KEY WORDS: minimally invasive surgery - SILS - double incision laparoscopic surgery.

Mid-infrared supercontinuum generation in suspended core tellurite microstructured optical fibers.

We report the fabrication of a tellurite optical fiber with a suspended core design, formed on a 220-nm-wide filament of glass. The fiber was pumped at two different wavelengths (1500 and 2400 nm) using femtosecond pulses generated from an optical parametric oscillator (OPO) in order to produce mid-infrared supercontinuum (SC). We observed that SC spectra extending to 3 µm were readily generated. To further optimize the design, detailed numerical study was performed, which revealed how the fiber structural characteristics dramatically influence the spectral broadening because of the changes in the dispersion profile and in turn, the interplay of nonlinear effects that give rise to SC generation. We found that an accurate control of the core shape can be employed to contain the generated SC spectra within well-defined spectral regions or to provide a broad extension of the continuum to beyond 4 µm.

Adherence to oral bisphosphonates: 30 more minutes in dosing instructions matter.

OBJECTIVES: Low adherence to treatment with bisphosphonates significantly impedes its effectiveness. The objectives were: (1) to compare adherence to oral weekly and monthly bisphosphonates with emphasis on dosing instructions; and (2) to study associations between adherence and beliefs about the bisphosphonate treatment among women ≥ 55 years. METHODS: A multicenter survey was performed in secondary-care patients with osteoporosis. Osteoporosis Specific Morisky Medication Adherence Scale (OS-MMAS), questions on compliance with five dosing instructions and Beliefs about Medicines Questionnaire (BMQ) Specific were used. RESULTS: As many as 363 questionnaires (response rate 95%) were analyzed. Respondents (mean age 69 years) were treated with weekly bisphosphonates (37%) or monthly ibandronate (63%). Based on OS-MMAS, 67% of respondents showed high adherence with no differences between the subgroups. Only 44% of respondents were compliant with all dosing instructions. Compliance with dosing instructions concerning time interval (fasting and staying upright) was 71% in weekly and 52% in monthly subgroups, respectively (p < 0.001). Compliance with dosing instructions correlated positively with education (p = 0.009). The mean BMQ necessity score of 18.4 was greater than the mean BMQ concerns score of 13.3. OS-MMAS score correlated with necessity (p = 0.010). Persistence derived from OS-MMAS correlated with both necessity (p = 0.014) and concerns (p = 0.041). CONCLUSION: Despite relatively high adherence to the treatment, most patients do not follow dosing instructions. Reduced bioavailability, particularly of monthly ibandronate, can be expected in clinical practice. Adherence-related outcomes are associated with beliefs about the oral treatment with bisphosphonates.