Predicting Effective Adaptation to Breast Cancer to Help Women BOUNCE Back: Protocol for a Multicenter Clinical Pilot Study.

BACKGROUND: Despite the continued progress of medicine, dealing with breast cancer is becoming a major socioeconomic challenge, particularly due to its increasing incidence. The ability to better manage and adapt to the entire care process depends not only on the type of cancer but also on the patient's sociodemographic and psychological characteristics as well as on the social environment in which a person lives and interacts. Therefore, it is important to understand which factors may contribute to successful adaptation to breast cancer. To our knowledge, no studies have been performed on the combination effect of multiple psychological, biological, and functional variables in predicting the patient's ability to bounce back from a stressful life event, such as a breast cancer diagnosis. Here we describe the study protocol of a multicenter clinical study entitled "Predicting Effective Adaptation to Breast Cancer to Help Women to BOUNCE Back" or, in short, BOUNCE. OBJECTIVE: The aim of the study is to build a quantitative mathematical model of factors associated with the capacity for optimal adjustment to cancer and to study resilience through the cancer continuum in a population of patients with breast cancer. METHODS: A total of 660 women with breast cancer will be recruited from five European cancer centers in Italy, Finland, Israel, and Portugal. Biomedical and psychosocial variables will be collected using the Noona Healthcare platform. Psychosocial, sociodemographic, lifestyle, and clinical variables will be measured every 3 months, starting from presurgery assessment (ie, baseline) to 18 months after surgery. Temporal data mining, time-series prediction, sequence classification methods, clustering time-series data, and temporal association rules will be used to develop the predictive model. RESULTS: The recruitment process stared in January 2019 and ended in November 2021. Preliminary results have been published in a scientific journal and are available for consultation on the BOUNCE project website. Data analysis and dissemination of the study results will be performed in 2022. CONCLUSIONS: This study will develop a predictive model that is able to describe individual resilience and identify different resilience trajectories along the care process. The results will allow the implementation of tailored interventions according to patients' needs, supported by eHealth technologies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095675; https://clinicaltrials.gov/ct2/show/NCT05095675. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34564.

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018.

BACKGROUND: Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland. METHODS: We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected. RESULTS: A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients. CONCLUSIONS: To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.

Decreasing trend in the incidence of serious pneumonias in Finnish children with juvenile idiopathic arthritis.

OBJECTIVES: Children with juvenile idiopathic arthritis (JIA) may be predisposed to serious pneumonia due to modern disease-modifying anti-rheumatic treatment. In this nationwide retrospective study with clinical data, we describe the pneumonia episodes among children with JIA. METHODS: Patients under 18 years of age with JIA and pneumonia during 1998-2014 were identified in the National Hospital Discharge Register in Finland. Each individual patient record was reviewed, and detailed data on patients with JIA and pneumonia were retrieved, recorded, and analyzed. If the patient was hospitalized or received intravenous antibiotics, the pneumonia was considered serious. RESULTS: There were 157 episodes of pneumonia among 140 children with JIA; 111 episodes (71%) were serious (80% in 1998-2006 and 66% in 2007-2014). The mean age of the patients was 9 years. Forty-eight percent had active JIA and 46% had comorbidities. Disease-modifying anti-rheumatic drugs (DMARD) were used at the time of 135 episodes (86%): methotrexate (MTX) by 62% and biologic DMARDs (bDMARD) by 30%. There was no significant difference in the use of bDMARDs, MTX and glucocorticoids between the patient groups with serious and non-serious pneumonia episodes. During six of the episodes, intensive care was needed. Two patients (1.3%) died, the remaining ones recovered fully. CONCLUSIONS: Although the incidence of pneumonia and the use of immunosuppressive treatment among children with JIA increased from 1998 to 2014, the proportion of serious pneumonias in these patients decreased. There was no significant difference in the use of anti-rheumatic medication between patients with serious and non-serious pneumonia.Key Points• The incidence of serious pneumonias decreased from 1998 to 2014 among children with juvenile idiopathic arthritis (JIA).• There was no significant difference in the use of the disease-modifying anti-rheumatic medication between JIA patients with serious and non-serious pneumonias.• Active JIA, comorbidities, and combination medication were associated with nearly half of the pneumonias.

Tuberculosis in people with rheumatic disease in Finland 1995-2007: a nationwide retrospective register study.

OBJECTIVES: RA and its medication, especially TNF-α inhibitors, increase the risk of clinical tuberculosis (TB) infection. We aimed to investigate the clinical manifestations, incidence and temporal changes in TB occurring concurrently with rheumatic diseases (RDs) between 1995 and 2007. METHODS: We combined the register of the Social Insurance Institution of Finland and the National Infectious Disease Register to find adult patients with reimbursed DMARDs and with a TB notification between 1995 and 2007. After reviewing the medical records, we described their clinical manifestations and medications, explored TB incidence trends using Poisson regression, and compared the incidence of TB with that of the general population. RESULTS: We identified 291 patients with both TB and rheumatic disease (RD), 196 of whom had RA. Between 1995 and 2007, the incidence of TB in adult RD decreased from 58.8 to 30.0 per 100 000 (trend P < 0.001, average marginal effect -3.4/100 000 per year, 95% CI -4.4, -2.4). Compared with the general population, the incidence was ∼4-fold. Among RD patients, pulmonary TB was the most common form of TB (72.6%). Disseminated TB was present in 56 (19.6%) patients. CONCLUSION: The incidence of TB among RD patients was ∼4-fold that of the general population, and it declined between 1995 and 2007. Disseminated TB was present in nearly 20% of patients.

Pneumonia in children with juvenile idiopathic arthritis in Finland 1999-2014: a nationwide retrospective register linkage study.

OBJECTIVES: To compare the incidence of pneumonia in children with juvenile idiopathic arthritis (JIA) to the aged-matched general population and to evaluate the use of anti-rheumatic medication among children with JIA and pneumonia. METHODS: The National Hospital Discharge Register collects data on ICD-diagnoses of hospital patients in Finland. From this register, patients with JIA under 18 years of age with pneumonia from 1999 through 2014 were identified. The control group consisted of age-matched patients derived from the general population with a diagnosis of pneumonia made in the same calendar year as the pneumonia of the JIA patients. The patient records of the children with JIA were scrutinised for the use of anti-rheumatic medication. RESULTS: We identified 223 pneumonias among the JIA patients (56,161 patient-years) and 53,058 pneumonias in the control group (17,546,609 person-years). The incidence of pneumonia in children with JIA was 386 (annual range 131-639) and in the control group 303 (annual range 225-438) per 100,000 person-years. The incidence of pneumonia increased significantly over time among JIA patients (p=0.013) and in the control group (p<0.001). Through 2007-2014 the rate of pneumonia was significantly higher among children with JIA (p<0.001) than control children. We found 150 JIA patients with pneumonia confirmed by positive chest radiograph. Altogether 47% of the JIA patients had combination medication. The use of methotrexate and biologic agents increased significantly over time (p=0.016 and p<0.001, respectively). CONCLUSIONS: The incidence of pneumonia increased in children with JIA and in the general population from 1999 to 2014. During 2007-2014 JIA patients had a significantly higher rate of pneumonia than age-matched controls. The use of active anti-rheumatic medication was common.

Bloodstream infections among children with juvenile idiopathic arthritis: a prospective study from the onset of disease.

OBJECTIVES: To describe the incidence and nature of bloodstream infections (BSI) among children with juvenile idiopathic arthritis (JIA) followed-up prospectively from disease onset. METHODS: The Social Insurance Institution's (SII) national register on individuals with reimbursement for medication of chronic diseases was used to identify children with JIA from 2004 through 2011 and their medications. The National Infectious Disease Register (NIDR) collects data of all blood culture positive samples from all microbiology laboratories in Finland. We combined the NIDR and SII registers to identify JIA patients with BSI. Clinical and laboratory data of each JIA-BSI patient were collected from hospital records. RESULTS: There were 1604 JIA patients and 6630 person-years of follow-up. Five patients had BSI. During the first 5 years after diagnosis the cumulative emergence of BSI was 0.38% [95% confidence interval (CI) 0.16% to 0.92%]. The incidence rates were 7.5/10 000 follow-up years for JIA (95% CI 2.4-17.6) and 2.8/10 000 follow-up years for the age-matched general population (95% CI 2.7-2.9). The standardised incidence ratio was 3.0 (95% CI 1.2 to 7.2). The causative bacteria were Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli and Fusobacterium necrophorum. Three patients were on anti-rheumatic drugs, including two on TNF inhibitors. All patients responded rapidly to antimicrobial therapy and recovered uneventfully. CONCLUSIONS: Although BSI is rare among children with JIA, the incidence is 3-fold higher than among the general population.

Molecular epidemiology of Saccharomyces cerevisiae in an immunocompromised host unit.

Saccharomyces cerevisiae is increasingly recognized clinically, and repeated isolations from patients on a hematology unit in Turku, Finland, led to an epidemiologic investigation. Isolates were recovered from multiple body sites of 23 patients (n = 180) from 1994 to 1995 and from 29 patients (n = 45) from 1997 to 2002; these plus 2 from the hospital kitchen were identified as S. cerevisiae. Isolates were genotyped by restriction fragment length polymorphism (RFLP) of genomic DNA after EcoR1 digestion. Of 108 isolates, 97 (95 patient isolates and 2 from the hospital kitchen) were DNA group B and identical in RFLP pattern. The remaining 11 isolates were DNA group A; 2 patients that shared a room had identical group A isolates, both converted to DNA group B type colonization within 2 months. In almost all patients, S. cerevisiae was first recovered after admission. These data suggest an endemic source of colonizing organisms, possibly from the hospital food preparation area.

Successful management of cerebral and pulmonary mucormycosis with liposomal amphotericin B in a 28-year-old woman with acute lymphoblastic leukemia.

A 28-year-old woman with acute lymphoblastic leukemia developed fever and unilateral pleural based pulmonary infiltrate during prolonged chemotherapy induced neutropenia. CT-guided lung biopsy confirmed the diagnosis of pulmonary mucormycosis and liposomal amphotericin B therapy was started. A few days after the initial symptoms, the patient developed convulsions and a brain abscess was detected in computerized tomography and magnetic resonance imaging. Fungal hyphae detected in histopathological examination of a brain biopsy had identical morphology with those seen in previous lung biopsies. The patient was treated with liposomal amphotericin B for five months and cytotoxic chemotherapy was successfully completed during antifungal therapy. Pulmonary infiltrates and the brain abscess resolved and the patient received an allogeneic bone marrow transplantation from a matched, unrelated donor. Antifungal therapy was continued for one additional month after bone marrow transplantation to prevent a relapse of invasive mucormycosis. Follow-up of the patient revealed no signs of relapse of invasive mucormycosis but two months after successful bone marrow transplantation the patient developed lethal cytomegalovirus pneumonitis which was confirmed by autopsy. No signs of mucormycosis were detected at post-mortem.

Semiquantitative detection by real-time PCR of Aspergillus fumigatus in bronchoalveolar lavage fluids and tissue biopsy specimens from patients with invasive aspergillosis.

A real-time PCR method was developed and used to detect Aspergillus fumigatus mitochondrial DNA (mtDNA) in bronchoalveolar lavage (BAL) fluids and tissue biopsy specimens. The analytical sensitivity of the assay was one A. fumigatus conidium per reaction, and the assay was linear at least over 4 orders of magnitude above the detection limit. BAL fluids from 66 immunocompromised patients at risk of invasive pulmonary aspergillosis (IPA) and 33 immunocompetent controls and tissue biopsy specimens from 10 immunocompromised patients were analyzed. The results were related to the clinical diagnosis established according to recently published consensus criteria. A. fumigatus mtDNA positivity was encountered in 16 of 81 (20%) BAL fluid specimens from patients at risk and 1 of 33 (3%) specimens from immunocompetent controls. PCRs were positive in six of seven, two of four, and four of five of the patients with proven, probable, and possible IPA, respectively, as well as in four patients at risk but without any other evidence of IPA. With qualitative detection, the diagnostic sensitivity of PCR was 73%, specificity was 93%, and predictive values of positive (PPV) and negative (NPV) results were 73 and 95%, respectively. Using a threshold cycle of <35 as a limit for positive PCR, the specificity and PPV of PCR in the diagnosis of invasive aspergillosis were 100%, but its sensitivity was only 45% and NPV was 92%. PCR was positive in tissue biopsy specimens from all patients with invasive aspergillosis caused by A. fumigatus. Semiquantitative detection of A. fumigatus mtDNA in BAL fluid may be helpful in the diagnosis of IPA. PCR is well suited for the verification of the presence of A. fumigatus in tissue biopsy specimens.