Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Cystic fibrosis patient characteristics and healthcare resource utilization in Finland using linked registries.

Background: Knowledge of prevalence and epidemiology of cystic fibrosis (CF) and healthcare resource use among Finnish people with CF is incomplete. Methods: We conducted a population-based matched cohort study using retrospective real-world data from linked Finnish national registries. Electronic healthcare data and drug purchases of 102 people with CF were analyzed between January 2015 and December 2019 (follow-up). A 5-fold control population was matched by sex, age, and place of residence. Comorbidities and medication use that occurred at any time during follow-up were assessed; annual rates of hospital service use were adjusted for follow-up. Results: The prevalence of CF in Finland was 1.85 per 100,000. Median age at diagnosis was 1 year, with 60 % diagnosed at age <2 years and 80 % at age <10 years. Median age at death in people with CF was 31.4 years (n < 5); no controls died. The most common comorbidities included chronic sinusitis (39.2 %), pneumonia (38.2 %), diabetes (20.6 %), and nasal polyps (18.6 %). The most purchased medications were antibiotics (99.0 %) and pancreatic enzymes (84.3 %). The annualized rate of hospital visits was higher in people with CF vs controls (outpatient: mean [SD], 17.4 [14.5] vs 0.9 [3.3]; median, 13.6 vs 0.4, respectively; inpatient: mean [SD], 1.0 [1.66] vs 0.03 [0.14]; median, 0.34 vs 0, respectively). Conclusions: The prevalence of CF in Finland is remarkably low, likely reflecting unique population characteristics and, in part, delayed diagnosis. Antibiotic use is frequent among Finnish people with CF. Inpatient hospital visits are >30 times higher in people with CF than matched controls.

Predictors of work status and quality of life 9-13 years after aneurysmal subarachnoid hemorrahage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) causes long-term psychosocial impairments even in patients who regain functional independence. Little is known about predictors of these impairments. We studied how early clinical data and neuropsychological results predict work status and health-related quality of life (HRQoL) 9-13 years after SAH. METHODS: One hundred one patients performed a neuropsychological test battery and returned their self-rating and partner's rating of a psychosocial impairment questionnaire approximately 1 year after SAH. These data were analyzed for association to the patients' work status and self-rated HRQoL approximately 10 years later. RESULTS: Age inversely, lower levels of self-rated impairments, employment and higher levels of education at the first follow-up independently predicted employment at the long-term follow-up. Although most cognitive test results were significantly associated with employment status at the long-term follow-up, they were of limited additional value as predictors of work status. The best predictor combination for long-term high HRQoL was good performance in a face recognition test and lower levels of self-rated impairments at the first follow-up as well as male sex. Problems in usual activities at the long-term follow-up were predicted by poor results in the face recognition and in a word list-learning task. CONCLUSION: Questionnaire ratings of patients' psychosocial impairments 1 year after SAH give important information for the long-term prediction of their work status and HRQoL. In the long run, patients' unemployment becomes strongly associated with higher age, while their performance of usual activities can be predicted with learning and memory results.

Survival and outcome of neurosurgical patients requiring ventilatory support after intensive care unit stay.

OBJECTIVE: The aim of this study was to analyze the clinical outcome of severely ill neurosurgical patients whose need for artificial life support was extended. We sought to determine whether these patients benefit from extended treatment both in life expectancy and quality of life. Furthermore, we evaluated the direct cost of the neurosurgical treatment. METHODS: The study group comprised a consecutive series of 346 neurosurgical patients in poor condition who were discharged from the intensive care unit but still in need of artificial respiratory support. The patients had various neurosurgical diagnoses and were treated between 2000 and 2003 at the Department of Neurosurgery, Helsinki University Central Hospital. We followed the outcome of these patients by specially formatted questionnaires 6 months and 1, 2, and 5 years after treatment. Their health-related quality of life was evaluated with EuroQol EQ-5D; quality-adjusted life years (QALY) gained with the treatment and the costs of a QALY were calculated. RESULTS: The median follow-up time was 5 years. The mortality rate was 27% at 30 days, 45% at 1 year, and 59% at 5 years after treatment. Of the patients, 20% had a good recovery (Glasgow Outcome Scale [GOS] scores 4 and 5), 18% had severe disability (GOS score 3), none was in a vegetative state (GOS score 2), 59% were dead (GOS score 1), and 3% were lost to follow-up. Of the survivors, 69% lived at home, 22% in a nursing home, 2% were in a hospital, and 7% were lost to follow-up. The median EQ-5D index value was lower than the median index value for the general population: 0.71 (25th percentile [Q1] 0.38 and 75th percentile [Q3] 0.85) versus 0.85 (Q1 0.73 and Q3 1.00). The median cost of the direct neurosurgical treatment per patient was 15,000 euros (25th percentile, 10,000 euros 75th percentile, 22,000 euros). Surviving patients gained a mean of 17 +/- 13 QALYs. The cost of 1 QALY was 2521 euros. CONCLUSION: Prolonged intensive care unit and step-down unit treatment of critically ill neurosurgical patients seems to be clinically justified. Moreover, direct costs of neurosurgical treatment were reasonably low.