Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.

Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535).

"When I was Younger, My Story Belonged to Everyone Else": Co-production of Resources for Adults Living with Craniosynostosis.

Objective: Despite growing recognition that congenital craniofacial conditions have lifelong implications, psychological support for adults is currently lacking. The aim of this project was to produce a series of short films about living with craniosynostosis in adulthood, alongside a psychoeducational booklet.

Design: The resources were developed using multiple focus groups and meetings attended by researchers, patient representatives, a leading charitable organisation, an award-winning film production company, clinicians, and other experts in the field.

SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

Background: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described.

Methods: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive.

Results: Of 9012 participants, 2270 (25.

Association of Self-reported Systemic Reactions Following SARS-CoV-2 Vaccination With Immunological Response in the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE).

Background: Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged if SARS-CoV-2 vaccines were known to lead to a stronger immune response.

Methods: Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post-vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe).

Assessing the impact of transplant case management on clinical outcomes.

Objectives: Case management is commonly used by health plans to attempt to improve the care received by their members who have complex needs, such as those who undergo transplantation. There are few observational studies evaluating the effects that transplant case management programs have on clinical outcomes following a solid organ transplant. This limits the understanding of the quantitative effectiveness of such programs.

Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens.

Background: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study.

Methods: PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and ≥1 follow-up BMI assessment available.

Increased incidence rates of positive blood cultures shortly after chemotherapy compared to radiotherapy among individuals treated for solid malignant tumours.

Background: Cancer treatments suppress immune function and are associated with increased risk of infections, but the overall burden of serious infectious diseases in treated patients has not been clearly elucidated.

Methods: All patients treated for solid malignant tumours with radiotherapy (RT) and/or standard first-line chemotherapy (C) at the Department of Oncology at Rigshospitalet between 01/1/2010 and 31/12/2016 were included. Patients were followed from treatment initiation until the first of new cancer treatment, 1 year after treatment initiation, end of follow-up or death.

Patient-reported outcomes in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer receiving olaparib versus chemotherapy in the OlympiAD trial.

Background: The phase III OlympiAD study (NCT02000622) showed a statistically significant progression-free survival benefit with olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA mutation and human epidermal growth factor receptor 2-negative metastatic breast cancer. From this study, we report the effect of olaparib on health-related quality of life (HRQoL).

Methods: Patients were randomised 2:1 to olaparib monotherapy (300 mg twice daily) or single-agent TPC.

Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment.

Background: Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially renally cleared. We investigated the pharmacokinetics and safety of olaparib in patients with mild or moderate renal impairment to provide dosing recommendations.

Methods: This phase I open-label study assessed the pharmacokinetics, safety and tolerability of single-dose, oral 300-mg olaparib tablets in adults (aged 18-75 years) with solid tumours.

Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors: Results of Two Phase I Open-label Studies.

Purpose: The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses.

Methods: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors.

Olaparib does not cause clinically relevant QT/QTc interval prolongation in patients with advanced solid tumours: results from two phase I studies.

Background: Some therapeutic agents in oncology can be causally associated with specific cardiovascular events including QT/QTc interval prolongation. We investigated the effect of multiple dosing of the oral poly (ADP-ribose)-polymerase (PARP) inhibitor, olaparib (tablet formulation) on QT/QTc interval.

Methods: Two phase I, open-label, three-part studies (NCT01921140 [study 4] and NCT01900028 [study 7]) were conducted in adults with refractory/resistant advanced solid tumours.

An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib.

Background: Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation.

A commercial transplant network's perspective of value in solid organ transplantation: Strategizing for value in transplant care.

Introduction: Solid organ transplantation has been an area of great interest to commercial payers ever since it moved into mainstream medical care beginning in the 1980s. Over the years a system of evaluating transplant program performance based on volume and one year graft and patient survival has developed. While this system has served its purpose, there is an increasing realization from payers that a need exists for a more sophisticated way to evaluate quality and cost-effectiveness of these complex procedures.

Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours.

Background: The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet formulation.

Methods: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed.

Chiropractic care and the risk of vertebrobasilar stroke: results of a case-control study in U.S. commercial and Medicare Advantage populations.

Background: There is controversy surrounding the risk of manipulation, which is often used by chiropractors, with respect to its association with vertebrobasilar artery system (VBA) stroke. The objective of this study was to compare the associations between chiropractic care and VBA stroke with recent primary care physician (PCP) care and VBA stroke.

Methods: The study design was a case-control study of commercially insured and Medicare Advantage (MA) health plan members in the U.

Effect of Food on the Pharmacokinetics of Olaparib after Oral Dosing of the Capsule Formulation in Patients with Advanced Solid Tumors.

Background: The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer.

Methods: This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout).

Economic value of a cancer case management program.

Purpose: To assess the impact of the cancer support program (CSP), a telephonic case management program led by oncology nurses, on cancer-related medical costs and hospice use.

Methods: Members of large employer-funded health plans were referred to the CSP if they had a cancer diagnosis and met program criteria. Patients were referred to the CSP (July 2009-June 2011; index date is referral date) and chose to participate (participants) or not (nonparticipants).

Aspirin-induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD(P)H oxidation.

In previous studies, we observed that aspirin, a promising cancer-preventive agent, induces apoptosis in mitochondrial manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae cells grown aerobically in ethanol medium. In this study, we show that aspirin-induced apoptosis is associated with a significant increase in mitochondrial and cytosolic O2 ·- and oxidation of mitochondrial NAD(P)H. A concomitant rise in the level of cytosolic CuZnSOD activity failed to compensate for mitochondrial MnSOD deficiency.

Detection of transient regional myocardial ischemia using body surface Delta map in patients referred for myocardial perfusion imaging--a pilot study.

Background: The diagnosis of transient regional myocardial ischemia (TRMI) in patients presenting with stable chest pain is a challenge. Exercise Tolerance Test (ETT) is no longer recommended in most cases due to its flaws. Alternative tests are more expensive and less readily available.

The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression.

Background: The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression.

Methods: A total of 3,780 patients from the EuroSIDA study under follow-up after 2001 with a current CD4(+) T-cell count ≤200 cells/mm(3) were stratified into five groups: group 1, viral load (VL)<50 copies/ml on cART; group 2, VL 50-99,999 copies/ml on cART; group 3, VL 50-99,999 copies/ml off cART; group 4, VL≥100,000 copies/ml on cART; and group 5, VL≥100,000 copies/ml off cART. Poisson regression was used to identify the risk of (non-fatal or fatal) AIDS- and non-AIDS-related events considered together (AIDS/non-AIDS) or separately as AIDS or non-AIDS events within each group.

Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam.

The objective of our study was to investigate factors associated with virological failure in 100 consecutive HIV-1 infected Vietnamese adults who initiated antiretroviral therapy (ART) from June 2007 to June 2008. Data were collected from medical records, and a structured questionnaire was used in individual interviews to investigate factors associated with adherence to ART. Plasma HIV viral load was measured at the time of the interview.

A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy.

Background: The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain.

Methods: The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses.

Tuberculosis among HIV-positive patients across Europe: changes over time and risk factors.

Objective: To describe temporal changes in the incidence rate of tuberculosis (TB) (pulmonary or extrapulmonary) among HIV-positive patients in western Europe and risk factors of TB across Europe.

Methods: Poisson regression models were used to determine temporal changes in incidence rate of TB among 11,952 patients from western Europe (1994-2010), and to assess risk factors for TB among 12,673 patients from across Europe with follow-up after 2001.

Results: Two hundred and seventy-seven TB events occurred during 84,221 person-years of follow-up (PYFU) in western Europe.

The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology.

Background: The Coding Causes of Death in HIV (CoDe) Project aims to deliver a standardized method for coding the underlying cause of death in HIV-positive persons, suitable for clinical trials and epidemiologic studies.

Methods: The project incorporates detailed data collection, a classification system, and a centralized adjudication process performed by 2 independent reviewers. The methodology was tested in the Data Collection on Adverse events of Anti-HIV Drugs Study , and independent reviews of causes of death were compared.