Livmorhalsprøvetaking i primærhelsetjenesten

BAKGRUNN I Norge ble det i 2020 tatt ca. 360 000 screeningprøver fra livmorhals, hvorav 11 000 ble registrert som uegnede. Vi ønsket derfor å undersøke kunnskap om livmorhalsprøvetaking blant leger i primærhelsetjenesten. MATERIALE OG METODE En anonym spørreundersøkelse om livmorhalsprøvetaking ble sendt på e-post til de ca. 4 700 medlemmene i Norsk forening for allmennmedisin i september 2021. RESULTATER Av de 1 039 legene som svarte på undersøkelsen, oppga 820 (79 %) at de alltid fyller ut årsak til prøvetaking i rekvisisjonen, og 898 (86 %) opplyste at de unngår å ta prøve ved menstruasjon. Bare én av tre leger (343) anga riktig lokalisering av overgangssonen hos postmenopausale kvinner. På spørsmål rettet til brukere av metoden som er spesielt følsom for prøvetakingsfeil (ThinPrep), svarte 426 av 697 (61 %) at de enten unngår eksplorasjonskrem eller bruker vannbasert krem, mens kun 35 % av legene svarte at de stopper prøvetakingen hvis blødning oppstår. FORTOLKNING Resultatene viser at selv om kunnskapen hos mange er god, er kontinuerlig fokus på livmorhalsprøvetaking viktig. Riktig prøvetaking samt kjennskap til anatomiske forhold hos postmenopausale kvinner kan være av betydning for å redusere antallet uegnede prøver. Hovedfunn Leger i primærhelsetjenesten viste generelt god kunnskap om prøvetaking fra livmorhals, men 65 % kunne ikke angi korrekt hvor celleprøve skal tas hos postmenopausale kvinner. Blant legene som benyttet ThinPrep, stoppet 35 % prøvetaking hvis blødning oppsto, og 61 % svarte korrekt på spørsmål om bruk av eksplorasjonskrem.publishedVersio

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

Background: VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings: Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion: Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab

Throat infections and use of streptococcal antigen test and antibiotic treatment in general practice; a web-based survey

The aim of this study was to investigate the use of streptococcal antigen tests and antibiotic prescription in general practice in Norway in relation to the national guidelines for sore throat. This study was based on a web-based survey. Norwegian general practice. 4700 members of the Norwegian College of General Practice received the survey by E-mail. General practitioner (GP) adherence to national guidelines. In total, 807 GPs responded and were included in the study. According to the guidelines, 20% and 30% of the GPs would perform unnecessary streptococcal antigen testing when presented with mild and severe infections respectively, while 52% would not perform the test at moderate infection. Phenoxymethylpenicillin was recommended by 95% of the GPs. In this survey of self-selected GPs, we identified some non-adherence to National guidelines for streptococcal antigen testing and antibiotic prescribing. However, when antibiotic treatment was offered, the correct antibiotics were prescribed.Key pointsNorwegian guidelines for diagnosis and treatment of throat infections include the use of Centor criteria as a clinical tool to limit the unnecessary use of antibiotics. In this web-based survey, we investigated the use of streptococcal antigen tests and antibiotic prescription in general practice in relation to the national guidelines.•Streptococcal antigen tests were not always performed according to Norwegian guidelines, causing inappropriate antibiotic prescribing.•National guidelines were followed in the choice of antibiotics for sore throat. Norwegian guidelines for diagnosis and treatment of throat infections include the use of Centor criteria as a clinical tool to limit the unnecessary use of antibiotics. In this web-based survey, we investigated the use of streptococcal antigen tests and antibiotic prescription in general practice in relation to the national guidelines. •Streptococcal antigen tests were not always performed according to Norwegian guidelines, causing inappropriate antibiotic prescribing. •National guidelines were followed in the choice of antibiotics for sore throat.</p

ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab

Bevacizumab is included in an increasing number of clinical trials. To find biomarkers to predict and monitor treatment response, cancer and angiogenesis relevant mutations in tumour and circulating tumour DNA (ctDNA) were investigated in 26 metastatic melanoma patients treated with bevacizumab. Patients with >1% BRAF/NRAS ctDNA at treatment start had significantly decreased progression free survival (PFS) and overall survival (OS) (PFS: p = 0.019, median 54 vs 774 days, OS: p = 0.026, median 209 vs 1064 days). Patients with >1% BRAF/NRAS ctDNA during treatment showed similar results (PFS: p = 0.002, OS: p = 0.003). ≤1% BRAF/NRAS ctDNA and normal lactate dehydrogenase (LDH) levels both significantly predicted increased response to treatment, but BRAF/NRAS ctDNA was better at predicting response compared to LDH at treatment start (OR 16.94, p = 0.032 vs OR 4.57, p = 0.190), and at predicting PFS (HR 6.76, p = 0.002) and OS (HR 6.78, p = 0.002) during therapy. ctDNA BRAF p.V600D/E/K and NRAS p.G12V/p.Q61K/L/R were better biomarkers for response prediction than TERT promoter mutations (OR 1.50, p = 0.657). Next generation sequencing showed that all patients with ≥2 mutations in angiogenesis-relevant genes had progressive disease, but did not reveal other biomarkers identifying responders. To conclude, ctDNA and LDH are useful biomarkers for both monitoring and predicting response to bevacizumab

Computed tomography showing partial responses in three different patients at baseline and at 12 months.

<p>Panel A shows ovarian metastases in a 43 years old woman. Panel B shows lung metastases in a 50 years old man. Panel C shows liver metastases and pleural effusion (*) in a 70 years old man. Arrows show the largest diameter of the lesions.</p

Baseline Demographic and Clinical Characteristics of Patients.

<p>Abbreviations: LDH, lactate dehydrogenase; ULN, upper limit of normal; WHO, World Health Organization.</p

Patterns of response to treatment with bevacizumab monotherapy in metastatic malignant melanoma patients.

<p>Panel A shows the best overall response for 32 patients who had undergone at least one tumor assessment measured as the change from baseline in the sum of the largest diameters of each target lesion. Three patients progressed clinically and/or biochemically before first tumor assessment, and are not shown. Negative values indicate tumor shrinkage, and the dashed lines indicate the threshold for a partial response (PR) and progressive disease (PD), respectively. Panel B shows the duration and characteristics of the responses in each patient.</p

Study flow diagram.

<p>Between April 2005 and August 2009, 52 patients with metastatic melanoma were screened. Thirty-five of those patients were eligible according to inclusion criteria and received the study drug.</p

Kaplan Meyer plots of progression free survival (PFS) (A) and overall survival (OS) (B) in 35 metastatic melanoma patients treated with bevacizumab monotherapy.

<p>Early hypertension (EH) was significantly associated with PFS (C) and OS (D).</p

Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants

Background CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype. Methods All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced. Results Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p&lt;0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010). Conclusion Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation