Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes.

BACKGROUND: The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up. METHODS: We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns. RESULTS: Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model. CONCLUSION: The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.

Reduced long-term mortality after successful resective epilepsy surgery: a population-based study.

BACKGROUND: We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. METHOD: Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. RESULTS: SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic-clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. CONCLUSIONS: In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

Prehospital lactate levels in blood as a seizure biomarker: A multi-center observational study.

OBJECTIVE: The objective of this study was to assess the value of prehospital measurement of lactate level in blood for diagnosis of seizures in cases of transient loss of consciousness. METHODS: Between March 2018 and September 2019, prehospital lactate was measured with a point-of-care device by the emergency medical services in an area serving a population of 900 000. A total of 383 cases of transient loss of consciousness were identified and categorized as tonic-clonic seizure (TCS), other seizure, syncope, or other cause, according to the final diagnosis in the electronic medical records system. Receiver operating characteristic curve analyses were used to identify the optimal lactate cut-off. RESULTS: A total of 383 cases were included (135 TCS, 42 other seizure, 163 syncope, and 43 other causes). The median lactate level in TCS was 7.0 mmol/L, compared to a median of 2.0 mmol/L in all other cases (P < .001). The area under the curve (AUC) of TCS vs nonepileptic causes was 0.87 (95% confidence interval [CI] 0.83-0.91). The optimal cut-off (Youden index, 67.8%) was 4.75 mmol/L, with 79% sensitivity (95% CI 71-85) and 89% specificity (95% CI 85-93) for TCS. SIGNIFICANCE: Prehospital lactate can be a valuable tool for identifying seizures in transient loss of consciousness. For acceptable specificity, a higher cut-off than that previously demonstrated for hospital-based measurements must be used when values obtained close to the time of the event are interpreted.

Low IQ predicts worse long-term seizure outcome after resective epilepsy surgery - A propensity score matched analysis.

OBJECTIVE: To describe long-term seizure outcomes in patients with IQ < 70 undergoing resective epilepsy surgery and to analyse whether baseline IQ predicts seizure outcome. METHODS: Patients undergoing focal resective epilepsy surgery 1995-2017 at age ≥ 4 years were identified in the population-based Swedish National Epilepsy Surgery Register. Two-year, five-year and long-term (10-20-year follow-up) outcomes were analysed. Seizure outcomes of patients with IQ ≥ 70 and IQ < 70 at baseline were compared in the full cohort and between propensity score matched groups. RESULTS: Follow-up data were available for 884 patients, 79 of whom had IQ < 70. Matched controls were found for 74 of the IQ < 70 patients. Preoperative MRI pathology was unifocal in 54 % and 79 % of IQ < 70 and IQ ≥ 70 patients before matching compared to 58 % and 62 % after matching, respectively. Patients with IQ < 70 achieved significantly worse seizure outcomes at all time points both when analysing the full cohort and the matched groups. After matching, the proportions of seizure-free patients in the IQ < 70 group were 28 %, 32 % and 32 % at the 2-year, 5-year and long-term follow-ups, respectively. Corresponding figures in the IQ ≥ 70 group were 54 %, 62 % and 60 % (p for difference between IQ groups 0.004, 0.002 and 0.049). In the IQ < 70 group, 36 %, 29 % and 45 % had a ≥ 75 % reduction in seizure frequency at the respective three follow-ups. CONCLUSION: Low preoperative IQ predicts lower chances of seizure freedom after resective epilepsy surgery and few patients with IQ < 70 remain completely seizure-free in the long term. Nevertheless, a significant proportion had a reduction in seizure frequency of at least 75 % at long-term follow-up, indicating an important palliative potential of resective surgery for epilepsy patients with intellectual disability.

Epilepsy surgery in patients with hypothalamic hamartomas - Population-based two-year and long-term outcomes.

OBJECTIVE: Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. METHODS: All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. RESULTS: Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. CONCLUSION: This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time.

Disturbance in the oropharyngeal microbiota in relation to antibiotic and proton pump inhibitor medication and length of hospital stay.

The aim of this study was to investigate the appearance of a disturbed oropharyngeal microbiota during hospitalization and explore the patient characteristics that maybe associated with such a disturbance. Oropharyngeal swabs were collected from 134 patients at hospital admission and every 3-4 days thereafter. The samples were cultivated to determine the presence of a disturbed microbiota, which, in turn, was subcategorized into respiratory tract pathogens, gut microbiota and yeast species. Demographics, medical history data and hospitalization events were compared. The percentage of disturbed oropharyngeal microbiota increased significantly with length of stay (LOS). Receiving antibiotic treatment during the hospitalization tended to be associated with a disturbed microbiota (OR 2.75 [0.99-7.60]). Proton pump inhibitor (PPI) medication and receiving antibiotics before hospitalization were associated with the development of a disturbed oropharyngeal microbiota with colonization of gut pathogens (OR 3.49 [1.19-10.2] and OR 4.52 [1.13-18.1], respectively), while acute hospital admission was associated with a lower risk of colonization of gut pathogens (OR: 0.23 [0.074-0.72]). The risk of developing a disturbed oropharyngeal microbiota increased with LOS in hospitalized patients. PPI medication and receiving antibiotics before hospitalization were independent risk factors for developing oropharyngeal colonization of gut pathogens.

Efficacy of Lactiplantibacillus plantarum 299 and 299v against nosocomial oropharyngeal pathogens in vitro and as an oral prophylactic treatment in a randomized, controlled clinical trial.

BACKGROUND: Disturbance in the oropharyngeal microbiota is common in hospitalized patients and contributes to the development of nosocomial pneumonia. Lactiplantibacillus plantarum 299 and 299v (Lp299 and Lp299v) are probiotic bacteria with beneficial effects on the human microbiome. AIM: To investigate how Lp299 and Lp299v affect the growth of nosocomial oropharyngeal pathogens in vitro and to evaluate the efficacy in vivo when these probiotics are administered prophylactically in hospitalized patients. METHODS: The in vitro effect of Lp299 and Lp299v on nosocomial respiratory tract pathogens was evaluated using two methods, the co-culture and agar overlay. In the clinical study, patients were randomized to orally receive either probiotics or placebo twice daily during their hospital stay. Oropharyngeal swabs were analyzed at inclusion and every fourth day throughout hospitalization. FINDINGS: All tested pathogens were completely inhibited by both Lp299 and Lp299v using the agar-overlay method. In the co-culture experiment, Lp299 and Lp299v significantly (p < 0.05) reduced the growth of all pathogens except for Enterococcus faecalis co-incubated with Lp299. In the clinical study, daily oral treatment with Lp299 and Lp299v did not influence the development of disturbed oropharyngeal microbiota or nosocomial infection. Proton pump inhibitors, antibiotics, and steroid treatment were identified as risk factors for developing disturbed oropharyngeal microbiota. CONCLUSIONS: Lp299 and Lp299v inhibited pathogen growth in vitro but did not affect the oropharyngeal microbiota in vivo. The ClinicalTrials.gov Identifier for this study is NCT02303301.

An online tool for information to women with epilepsy and therapeutic drug monitoring in pregnancy: Design and pilot study.

OBJECTIVE: Information to women with epilepsy on pregnancy-related antiseizure medication (ASM) issues and reliable tools for therapeutic drug monitoring (TDM) are important aspects of epilepsy care. We aimed to develop and test an online tool for patient education on pregnancy-related issues and communication with epilepsy nurses during pregnancy for women with epilepsy. METHODS: An existing national platform for online communication (1177.se) was used, and an online tool was developed by two epilepsy nurses, two neurologists, and an IT technician. The tool was launched as a complement to standard care, and patients deciding to use it were invited to participate in a survey of user experiences and knowledge questions. RESULTS: The online tool consists of two modules: one for patient education and one for TDM during pregnancy. The latter module allows scheduling of automatic reminders of blood tests that are sent to patients at set intervals. The epilepsy nurse can communicate results and suggested dose changes in the tool. A total of 48 women answered the survey: 28 had been invited to use the information module and 20 to use the TDM module. Patient experiences were generally good, and most users of the TDM module would prefer an online means of communication in future pregnancies. For epilepsy nurses, the tool provided good overview of patients currently pregnant and administrative advantages compared with traditional means of communication. SIGNIFICANCE: Online patient education and communication about TDM during pregnancy are feasible and can be a valuable part of future digitalization efforts in epilepsy care.

[Stereoelectroencephalography - a safe and effective procedure for epilepsy surgery evaluation]. / Stereo-EEG ­ en effektiv metod för att utreda svårbehandlad epilepsi.

In this paper, we report our experiences from the first 30 patients investigated with stereoelectroencephalography (SEEG) at Sahlgrenska University Hospital, Gothenburg, Sweden. Clinical, neurophysiological, and imaging data were reviewed. Twelve children and 18 adults with drug-resistant epilepsy underwent 33 SEEG procedures. 53% of the patients had normal brain MRI. In total, 347 SEEG electrodes were implanted (median 12 per patient). Twenty patients subsequently had resective surgery based on SEEG findings. Focal cortical dysplasia was found in all cases. In 45% of the patients, vicinity of eloquent cortex limited resections. Epilepsy surgery based on SEEG resulted in seizure freedom in 58% of the cases. Minor complications were seen in eight patients, all of which resolved without sequelae. No major complications were seen. SEEG is a safe and effective method to delineate cortical areas involved in seizure generation.

Risk Factors for Seizure Worsening After Epilepsy Surgery in Children and Adults: A Population-Based Register Study.

BACKGROUND: Increased seizure frequency and new-onset tonic-clonic seizures (TCS) have been reported after epilepsy surgery. OBJECTIVE: To analyze potential risk factors for these outcomes in a large cohort. METHODS: We studied prospectively collected data in the Swedish National Epilepsy Surgery Register on increased seizure frequency and new-onset TCS after epilepsy surgery 1990-2015. RESULTS: Two-year seizure outcome was available for 1407 procedures, and data on seizure types for 1372. Increased seizure frequency at follow-up compared to baseline occurred in 56 cases (4.0%) and new-onset TCS in 53 (3.9%; 6.6% of the patients without preoperative TCS). Increased frequency was more common in reoperations compared to first surgeries (7.9% vs 3.1%; P = .001) and so too for new-onset TCS (6.7% vs 3.2%; P = .017). For first surgeries, binary logistic regression was used to analyze predictors for each outcome. In univariable analysis, significant predictors for increased seizure frequency were lower age of onset, lower age at surgery, shorter epilepsy duration, preoperative neurological deficit, intellectual disability, high preoperative seizure frequency, and extratemporal procedures. For new-onset TCS, significant predictors were preoperative deficit, intellectual disability, and nonresective procedures. In multivariable analysis, independent predictors for increased seizure frequency were lower age at surgery (odds ratio (OR) 0.70 per increasing 10-yr interval, 95% CI 0.53-0.93), type of surgery (OR 0.42 for temporal lobe resections compared to other procedures, 95% CI 0.19-0.92), and for new-onset TCS preoperative neurological deficit (OR 2.57, 95% CI 1.32-5.01). CONCLUSION: Seizure worsening is rare but should be discussed when counseling patients. The identified risk factors may assist informed decision-making before surgery.

Long-term employment outcomes after epilepsy surgery in childhood.

OBJECTIVE: To analyze long-term employment outcomes in a population-based cohort of adults who underwent epilepsy surgery in childhood or adolescence and to compare the results to general population reference data. METHODS: Prospective data on epilepsy surgery procedures performed on patients <19 years of age between 1995 and 2012 were extracted from the Swedish National Epilepsy Surgery Register. Five-, 10-, 15- and 20-year follow-up data were analyzed. Patients aged ≥19 years at follow-up were eligible for inclusion. Educational attainment and employment status were analyzed in relation to seizure outcome. Education and employment outcomes of seizure-free patients with a preoperative IQ of ≥70 were compared to general population reference data. RESULTS: A total of 203 patients were included. The mean age at surgery was 13.6 years and 66% had IQ ≥70. Of these, a majority had attained at least high school education 5 years after surgery. Employment rates were 44%, 69%, 71%, and 77% at the 5-, 10-, 15-, and 20-year follow-ups, respectively. Seizure-free patients were significantly more likely to work full-time. Educational attainment and rates of full-time employment of seizure-free patients were similar to the general population. A majority of patients with IQ <70 had attended special education and were reliant on social benefits. CONCLUSION: Long-term overall employment rates were higher compared to most previous studies on surgery in adults. Seizure-free patients with a preoperative IQ ≥70 showed rates of full-time employment similar to the general population. Further research is needed to determine whether this also applies for occupational complexity and wages.

Socioeconomic outcome and access to care in adults with epilepsy in Sweden: A nationwide cohort study.

PURPOSE: Epilepsy has well-documented associations with low income and low education levels, but the impact of a patient's socioeconomic standing (SES) on the effects of epilepsy have been less studied. METHOD: We performed a register-based cross-sectional study and asked if SES was associated with more severe epilepsy or limited access to care in Sweden, where health care is universal, and if socioeconomic outcomes (employment and income) differed for persons with epilepsy (PWE) with different levels of educational attainment. The study cohort consisted of all adult patients with an epilepsy diagnosis in the Swedish patient register in 2000-2015 (n = 126,406) and controls (n = 379,131) matched for age, gender, and place of birth. RESULTS: Somatic and psychiatric comorbidities were more common in PWE, while education and income levels were lower. Among PWE, hospitalizations were more common in persons with lower income or education. Having at least one prescription written by a neurologist in the study period was more common in the high-income and high-education groups. Finally, although low educational attainment was associated with low levels of income and inversely associated with employment in both persons with epilepsy and controls, regression analyses demonstrated that these associations were much more noticeable in cases than controls. CONCLUSIONS: We conclude that both the severity and consequences of epilepsy are greater in persons of low SES, even in a country with universal health care. This indicates that universal access may not be sufficient to mitigate socioeconomic inequity in epilepsy.