The success of a screening program depends first of all on coverage and timely follow-up of abnormal findings. Our analysis indicated that the currently high incidence of cervical cancer in Denmark may partly be due to low screening coverage. Also worrisome is a high proportion of non-timely follow-up of abnormal findings. Innovative ways to improve coverage and follow-up are urgently needed.
Aim. In countries like Denmark, cervical cancer incidence is at present relatively high in elderly women, while routine screening stops at age 65 years. On this background, all women aged 69 and above were invited to human papillomavirus (HPV)-screening in Denmark in 2017.Methods. Women were identified from the Central Population Register and personally invited by digital or ordinary mail to have a screening sample taken by their general practitioner. In four regions, samples were tested for high risk (HPV) with the cobas 4800® HPV-assay, and in the last region with the BD Onclarity® HPV-assay. Participation rate, prevalence of high risk HPV, and proportion of positive samples with HPV16, HPV18, and other high risk HPV-types were tabulated by 5-year age-groups.Results. 455,612 women were invited, and 30.2% (95 confidence interval (CI) 30.0-30.3) participated. Average age of participants was 74.6 years. Overall, 4.3% (95% CI 4.1-4.4) of participants were HPV-positive, of whom 24% had HPV 16/18. HPV-prevalence decreased slightly from 4.5% in women aged 69-73 years to 3.1% in women aged 84-88 years, but was 5.2% in the very small group of participants aged 89+ years.Conclusion. Invitation to HPV-screening was well received by elderly women. The HPV-prevalence decreased slightly with increasing age. No rebound of HPV-prevalence after menopause was found when our data were combined with previously published Danish data from younger women. The presently relatively high cervical cancer incidence in elderly women was not reflected in the HPV-prevalence.
Breast cancer heterogeneity in histology and molecular subtype influences metabolic and proliferative activity and hence the acid load on cancer cells. We hypothesized that acid-base transporters and intracellular pH (pHi) dynamics contribute inter-individual variability in breast cancer aggressiveness and prognosis. We show that Na+,HCO3--cotransport and Na+/H+-exchange dominate cellular net acid extrusion in human breast carcinomas. Na+/H+-exchange elevates pHi preferentially in estrogen receptor-negative breast carcinomas, whereas Na+,HCO3--cotransport raises pHi more in invasive lobular than ductal breast carcinomas and in higher malignancy grade breast cancer. HER2-positive breast carcinomas have elevated protein expression of Na+/H+-exchanger NHE1/SLC9A1 and Na+,HCO3--cotransporter NBCn1/SLC4A7. Increased dependency on Na+,HCO3--cotransport associates with severe breast cancer: enlarged CO2/HCO3--dependent rises in pHi predict accelerated cell proliferation; whereas enhanced CO2/HCO3--dependent net acid extrusion, elevated NBCn1 protein expression, and reduced NHE1 protein expression predict lymph node metastasis. Accordingly, we observe reduced survival for patients suffering from Luminal A or Basal-like/triple-negative breast cancer with high SLC4A7 and/or low SLC9A1 mRNA expression. We conclude that the molecular mechanisms of acid-base regulation depend on clinicopathological characteristics of breast cancer patients. NBCn1 expression and dependency on Na+,HCO3--cotransport for pHi regulation, measured in biopsies of human primary breast carcinomas, independently predict proliferative activity, lymph node metastasis, and patient survival.
BACKGROUND Indications and optimal timing for surgical treatment of degenerative cervical myelopathy (DCM) remain unclear, and data from daily clinical practice are warranted. OBJECTIVE To investigate clinical outcomes following decompressive surgery for DCM. METHODS Data were obtained from the Norwegian Registry for Spine Surgery. The primary outcome was change in the neck disability index (NDI) 1 yr after surgery. Secondary endpoints were the European myelopathy score (EMS), quality of life (EuroQoL 5D [EQ-5D]), numeric rating scales (NRS) for headache, neck pain, and arm pain, complications, and perceived benefit of surgery assessed by the Global Perceived Effect (GPE) scale. RESULTS We included 905 patients operated between January 2012 and June 2018. There were significant improvements in all patient-reported outcome measures (PROMs) including NDI (mean −10.0, 95% CI −11.5 to −8.4, P < .001), EMS (mean 1.0, 95% CI 0.8-1.1, P < .001), EQ-5D index score (mean 0.16, 95% CI 0.13-0.19, P < .001), EQ-5D visual analogue scale (mean 13.8, 95% CI 11.7-15.9, P < .001), headache NRS (mean −1.1, 95% CI −1.4 to −0.8, P < .001), neck pain NRS (mean −1.8, 95% CI −2.0 to −1.5, P < .001), and arm pain NRS (mean −1.7, 95% CI −1.9 to −1.4, P < .001). According to GPE scale assessments, 229/513 patients (44.6%) experienced “complete recovery” or felt “much better” at 1 yr. There were significant improvements in all PROMs for both mild and moderate-to-severe DCM. A total of 251 patients (27.7%) experienced adverse effects within 3 mo. CONCLUSION Surgery for DCM is associated with significant and clinically meaningful improvement across a wide range of PROMs.
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