Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.     

Chronic Pain,Functional Status,and Life Satisfaction Are Associated With Patients Living With HIV Discussing Advance Care Planning With Their Family or Friends

Context

In the era of effective antiretroviral therapy, persons living with HIV/AIDS (PLWHA) are living longer, transforming HIV from a universally fatal disease to a serious chronic illness, warranting discussions between patients and their loved ones about advance care planning (ACP). Evidence is needed on factors associated with patients' likelihood to discuss ACP with loved ones.

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.     

Inferior stabilization of cementless compared with cemented dual-mobility cups in elderly osteoarthrosis patients: a randomized controlled radiostereometry study on 60 patients with 2 years’ follow-up

Background and purpose — Elderly patients may benefit from a dislocation low-risk dual-mobility (DM) articulation in total hip arthroplasty, but the best cup fixation method is unknown. We compared cup migration for cemented and cementless DM cups using radiostereometry.Patients and methods — In a patient-blinded randomized trial, 60 patients (33 female) with osteoarthritis were allocated to cemented (n = 30) or cementless (n = 30) Avantage DM cup fixation. Criteria were age above 70 years, and T-score above –4. We investigated cup migration, periprosthetic bone mineral density (BMD), and patient-reported outcome measures (PROMs) until 24 months postoperative follow-up.Results — At 24 months mean proximal cup migration was 0.11 mm (95% CI 0.00–0.23) for cemented cups and 0.09 mm (CI –0.09 to 0.28) for cementless cups. However, cementless cups generally migrated more than cemented cups at 12 and 24 months. Cemented cups had no measurable migration from 3 months’ follow-up, while cementless cups had not yet stabilized at 24 months in all rotations. Cementless cups showed statistically significantly more maximum total point motion (MTPM) at 12- and 24-month follow-up compared with cemented cups in patients with low systemic BMD (p = 0.01). Periprosthetic BMD changes did not statisticially significantly correlate to proximal migration in either cup fixation group (p > 0.05). PROMs improved similarly in both groups.Interpretation — Cemented cups were well fixed at 3 months. The cementless cups migrated more in patients with low BMD, showed an inconsistent pattern of migration, and migrated in different directions during the first and second year without tendency to stabilization. Cemented fixation of the Avantage DM cup seems safer in elderly patients

The most common indication for revision of a conventional primary total hip arthroplasty (THA) is aseptic loosening of the components (SHAR 2016, NJR 2017, DHAR 2018).Implant fixation method (i.e., cemented or cementless) in primary THA seems mainly based on the surgeon’s preference and national trends. The Danish Hip Replacement Registry report shows a decrease in the use of cemented cup fixation in osteoarthrosis (OA) patients above 70 years (DHAR 2018). This trend has also been described in the United Kingdom (UK) and Australian Joint Registries, while in Sweden and Norway cemented cup fixation is still the preferred fixation method in elderly patients (SHAR 2016, NAR 2017, NJR 2017).The dual-mobility (DM) concept, with 2 articulation surfaces and increased jump distance, may decrease the dislocation rate and increase range of motion compared with standard single mobility (SM) THAs. The long-term survival and the best fixation method of the newer Avantage Reload DM cup in elderly patients is currently unknown but retrospective studies on other types of primary DM THAs suggest acceptable survival rates (Batailler et al. 2017) .Excessive early (2-year) implant micromotion measured with radiostereometric analysis (RSA) is a strong predictor for later implant loosening and poor survival (Karrholm et al. 1997, Nieuwenhuijse et al. 2012, Pijls et al. 2012), and our primary aim was to investigate the early RSA-measured migration of cemented and cementless Avantage DM cups in elderly (> 70 years old) OA patients until 24 months’ follow-up. Secondary endpoints included systemic and periprosthetic bone mineral density (BMD) measurements, and clinical outcome scores.