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- Teede, Helena J, et al.
(författare)
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Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
- 2023
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Ingår i: Fertility and sterility. - 1556-5653. ; 120:4, s. 767-793
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Tidskriftsartikel (refereegranskat)abstract
- What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
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3. |
- Omran, Meis, et al.
(författare)
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Whole-Body MRI Surveillance : Baseline Findings in the Swedish Multicentre Hereditary TP53-Related Cancer Syndrome Study (SWEP53)
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- A surveillance strategy of the heritable TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li–Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults ≥18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours (thyroid cancer, disseminated upper GI cancer, and liver metastasis from a previous breast cancer). Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.
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- Girma Kebede, Betlehem, et al.
(författare)
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Communicative challenges among physicians, patients, and family caregivers in cancer care: An exploratory qualitative study in Ethiopia
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer is a growing concern in Ethiopia. Though communication is essential for the treatment process, few studies have looked at communication in Ethiopian cancer care. Due to the large number of patients and scarcity of resources, it is vital to understand how to manage consultations in order to effectively help as many patients as possible in this challenging work environment. Thus, research is needed to analyze and understand the communicative challenges experienced by physicians, patients, and family caregivers, in order to successfully handle patient care in practice. Objective We explore communication in Ethiopian cancer care and present the main challenges faced by physicians, patients, and family caregivers. Methods This explorative qualitative study was conducted at the Oncology Department of the Tikur Anbessa (Black Lion) Specialized Teaching Hospital (TASH) in Addis Ababa, Ethiopia. A triangulation of data collection methods was used: 91 audio-recorded, semi-structured interviews and 21 video-recordings of authentic interactions during hospital rounds. The aim was to obtain as complete a picture as possible of communication from the perspectives of physicians, patients, and family caregivers. The interviews were analyzed using thematic content analysis and the identified themes were supported by excerpts from the transcribed recordings. Results Eight themes emerged from the data. Workload and time pressure, in combination with restricted space for privacy, limited the possibilities for physicians to deliver detailed information and provide emotional support. Furthermore, patient literacy levels, in combination with no or little cancer awareness, financial problems, reliance on traditional and religious treatments, the stigma of cancer, and a fatalistic attitude, resulted in delays in patients seeking care and participating in positive health behaviors, and, subsequently, often resulted in an unwillingness to openly discuss problems with physicians and adhere to treatment. The study also illustrates the paramount role of family in physician-patient communication in Ethiopia. Though family caregivers provide a valuable interpreting support when patients have limited language skills, they can also prevent patients from sharing information with physicians. Another important finding is that family caregivers were often responsible for making decisions about treatment and avoided telling patients about a poor prognosis, believing that conveying bad news may upset them. All of these themes have important implications for the role of ethically acceptable communication in patient-centered care. Conclusions This study has identified a number of serious challenges for successful and ethically acceptable health communication in Ethiopian cancer care. The study contributes to our understanding of the complexity around the role of family, combined with patients’ dependency on family members for communication, support, and access to care, which creates particular ethical dilemmas for the medical staff. The questions raised by this study concern how to organize consultations to achieve patient-centered health communication, while maintaining a constructive alliance with the family and not jeopardizing the patient’s continued access to care. The integration of communication training for medical students in Ethiopia, with a focus on ethical guidelines for family-centered patient consultation suitable for these circumstances, would be an essential step.
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5. |
- Johnson, Heather, et al.
(författare)
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Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up
- 2020
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRTPCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. Conclusions: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.
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- Sorbe, Bengt, et al.
(författare)
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Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up
- 2008
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Ingår i: International Journal of Gynecological Cancer. - : Blackwell Publishing Ltd. - 1048-891X .- 1525-1438. ; 18:4, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.
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7. |
- Wilms, Torben, 1973-
(författare)
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Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
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8. |
- Browall, Maria, et al.
(författare)
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Information needs of women with recently diagnosed ovarian cancer - A longitudinal study
- 2004
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 8:3, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n=82) with recently diagnosed ovarian cancer was asked to participate.Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p=0.005).In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology. © 2004 Elsevier Ltd. All rights reserved.
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- Lönnbro-Widgren, Jennie, et al.
(författare)
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Glomerular IgG subclasses in idiopathic and malignancy-associated membranous nephropathy
- 2015
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 1753-0784 .- 1753-0792 .- 2048-8505 .- 2048-8513. ; 8:4, s. 433-439
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Tidskriftsartikel (refereegranskat)abstract
- Background: In idiopathic membranous nephropathy (MN), antibodies directed towards the glomerular phospholipase A2 receptor (PLA2R) have mainly been reported to be of IgG4 subclass. However, the role of the different IgG subclasses in the pathogenesis of MN, both in idiopathic MN and in secondary cases, is still unclear. In this retrospective study, we test the hypothesis that the absence of glomerular IgG4 and PLA2R in patients with MN indicates malignant disease. Methods: The distribution pattern of glomerular IgG subclasses and PLA2Rwas studied in 69 patients with idiopathicMNand 16 patients with malignancy-associated MN who were followed up for a mean of 83 months. Results: A significant correlation between the absence of IgG4 and PLA2R and malignancy-associatedMNwas found. Thus, IgG4 was positive in 45 of 69 patients (65%) with idiopathicMNbut only in 5 of 16 patients (31%) with malignancy-associated MN. The other IgG subclasses did not differ statistically between the groups, IgG2-positivity being present in more than 94% of patients in both groups. Thirty-five of 63 patients (56%) with idiopathic MN and 3 of 16 (19%) patients with malignancy-associated MN had glomerular deposits of PLA2R. Conclusions: We have found that the absence of glomerular IgG4 and PLA2R iscommonin patients with malignancy-associated MN. In our material, IgG2 could not be used as a marker of underlying malignant disease. Finally, neither IgG1 nor IgG3 seems to be involved in the pathogenesis of MN. © The Author 2015.
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- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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