Mild Cognitive Impairment in Rural Areas: Research Advances and Implications for Clinical Practice and Healthcare Policy.

Mild cognitive or neurocognitive impairment (MCI) may be more prevalent in rural areas. Differences between rural and urban MCI patients in terms of risk factors, course and prognosis are rarely reported. The present review aims to summarize the latest research on MCI in rural areas. A literature search was performed in the databases of PubMed, Scopus and ScienceDirect for articles published over the last decade. Eleven articles were included in this review, reporting on the differences between rural and urban MCI patients. Several risk factors, such as older age, lack of activities and food insecurity have been associated with MCI in both rural and urban areas, whereas others, such as obesity, adverse childhood experiences and plasma chemokine C-C motif ligand 11 (considered as a potential negative regulator of neurogenesis), differed according to the place of residence. No specific protective factor for rural women has been reported. There is some evidence that MCI may present earlier in rural residents, but that progression to dementia may be more rapid in urban residents. It seems that there may be clinically relevant differences in the onset, course and prognosis of MCI with regards to the place of residence (urban vs rural). Those differences should be taken into account for the design of health policies and service delivery across different settings.

An open study of valproate in subfertile men with epilepsy.

OBJECTIVES: The aim of the study was to assess whether, male patients with epilepsy, switching from valproic acid (VPA) to levetiracetam (LEV) or lamotrigine (LMG) critically improves sperm counts and parameters, increasing chance of patients' female partners to spontaneously conceive. MATERIALS AND METHODS: This is an observational prospective study recruiting all consecutive infertile male patients with epilepsy followed up at the outpatient Epilepsy Clinic of University Hospital of Ioannina, Northwest Greece. Infertile couples were referred to the Laboratory of Assisted Reproduction and Treatment of the University Hospital of Ioannina to conduct semen analysis. The first sample was collected while the patients were receiving VPA, and the second semen sample was collected after the patients were switched to LEV or LMG. RESULTS: Seventeen infertile male patients were recruited in the study. Nine patients were switched to LEV, and eight patients were switched to LMG. The mean sperm count increased after VPA withdraw P = .06. Motility was improved with an increase of total motility and non-progressive motility (P = .02 and P = .03, accordingly), whether sperm defects were decreased, mainly head defects (P = .03). Differences between patients switched to LEV or LMG were minimal and showed no significant findings. Spontaneous pregnancies were reported in three of the patients' partners, without any other clinical intervention offered to the couple. CONCLUSION: Switching from valproic acid to levetiracetam or lamotrigine improved sperm counts and other sperm parameters in subfertile male patients and increased the chance of spontaneously conceiving in subfertile couples.

Reproductive health in patients with epilepsy.

The aim of the present study was to review existing knowledge on the impact of epilepsy in reproductive health of both sexes. Extensive searches of relevant documentation published until February 2020 were retrieved from PubMed and Google Scholar literature in English or in other languages with an English abstract. In females, epilepsy may lead to estrogen and androgen level abnormalities. Women with epilepsy may develop Polycystic Ovaries Syndrome (PCOS), anovulatory cycles, and menstrual disorders. In men, epilepsy may cause sex hormone dysregulation and influence spermatogenesis. Males with epilepsy may also suffer from sexual dysfunction. Antiepileptic drugs (AEDs) have adverse effects on peripheral endocrine glands, influence hormones' biosynthesis and protein binding, diminish the bioactivity of serum sex hormones, and lead to secondary endocrine disorders related to changes concerning body weight and insulin sensitivity. Valproic acid (VPA) was the first recognized AED to cause disturbances potentially due to metabolic changes and increasing weight. Women taking VPA may develop PCOS, while men may have sperm abnormalities and/or sexual dysfunction. Liver enzyme inducing AEDs may also cause menstrual and sexual disorders in women and sexual dysfunction in men. Newer AEDs are much safer but studies still suggest reduced sexuality and erectile dysfunction.

Factors related to the adverse events of antiepileptic drugs.

OBJECTIVE: The aim of the present study was to explore the factors related to the severity of the adverse effects of antiepileptic drugs (AEDs), experienced by patients with epilepsy. MATERIALS AND METHODS: A case study was conducted in adult patients with epilepsy and followed up at the Epilepsy Outpatients of the University Hospital of Ioannina in Northwest Greece. The Adverse Event Profile (AEP) questionnaire for AEDs adverse effects assessment, the Defense style questionnaire (DSQ-88) and the Patient Health Questionnaire (PHQ-9) for depression' severity evaluation were used to estimate the severity of adverse effects, the defense style, and the depressive symptoms, respectively. RESULTS: Sixty-three patients with epilepsy (M/F:28/35), with a mean age of 37.6 ±â€¯13.41, were recruited in the study. The univariate analysis showed that both the Maladaptive style of defense and the PHQ-9 score were significantly associated with the AEP score. After multivariate regression analysis female gender, the load of AEDs, the PHQ-9 score, and the Adaptive defense style remained significant coefficients. CONCLUSION: There are also nonpharmacological factors that may contribute to the severity of the adverse effects of AEDs, experienced by the patients with epilepsy.

Psychological distress symptoms and illness perception in patients with epilepsy in Northwest Greece.

OBJECTIVE: The purpose of the present study was to compare psychological distress between patients with epilepsy and healthy controls and to evaluate potentially related factors to psychological distress in patients with epilepsy. Furthermore, we assessed how psychological distress and other potential factors mediate illness perception in patients with epilepsy in an urban area of Northwest Greece. MATERIALS AND METHODS: A case-control study was conducted in adult patients with epilepsy followed up at the University Hospital of Ioannina and in healthy controls. The Symptom Checklist-90 Revised (SCL-90R) for symptoms of psychological distress and the overall psychological distress Global Severity Index (GSI) evaluation, the brief illness perception questionnaire (B-IPQ), and the Adverse Event Profile (AEP) questionnaire for the antiepileptic drugs (AEDs) were used. RESULTS: Seventy patients with epilepsy and 70 controls were recruited in the study. Somatic, depression, and anxiety symptoms and the GSI were higher in patients than in controls. In patients with epilepsy, the AEP score was significantly associated with psychological distress. Illness perception was associated with the number and the total number of administered AEDs; the AEP score; somatic, obsessive, depressive, and anxiety symptoms; and the GSI. After regression analysis, epilepsy characteristics, AEDs, and psychological distress accounted for 11.7%, 28.7%, and 5.5% of variance in BIP-Q score, respectively. CONCLUSION: Screening for psychological distress in patients with epilepsy is of high importance in clinical practice as somatic, depression, and anxiety symptoms and overall psychological distress are more severe in patients with epilepsy than in healthy controls. The symptoms of psychological distress are strongly associated with the adverse effects of AEDs. The epilepsy characteristics, the AEDs, and the psychological distress could determine a large part of illness perception in epilepsy, with the adverse effects of AEDs being the strongest predictor.

Depression and quality of life in patients with epilepsy in Northwest Greece.

PURPOSE: The purpose of the present study was to compare depression and QoL between patients with epilepsy and healthy controls, evaluating potentially related factors to depression and QoL in patients with epilepsy in Northwest Greece. METHODS: A case study was conducted in adult patients with epilepsy followed up at the University Hospital of Ioannina and in healthy controls. The Patient Health Questionnaire (PHQ-9) for depression's severity evaluation, the WHOQOL-BREF questionnaire for the QoL estimation and the Adverse Event Profile (AEP) questionnaire for the Antiepileptic Drugs (AEDs) adverse effects assessment were used. RESULTS: Seventy patients with epilepsy and 70 controls were recruited. The PHQ-9 score was higher in patients compared to controls and slightly higher than reported in patients with epilepsy. PHQ-9 was significantly associated with the AEP score. Our patients had a poorer QoL compared to controls. The level of education, the AEP and the PHQ-9 scores were associated to QoL, the last two being the most powerful predictors of QoL. CONCLUSION: Patients with epilepsy in Northwest Greece had higher rates of depression than reported in patients with epilepsy and poorer QoL compared to controls. The adverse effects of AEDs were related to depression in our study, while the adverse effects of AEDs and depression were more powerful predictors of QoL compared to demographics and other characteristics of epilepsy.

Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting.

PURPOSE: The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. METHODS: A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. RESULTS: Patients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. CONCLUSIONS: In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV.

Effect of femoral tunnel placement for reconstruction of the anterior cruciate ligament on tibial rotation.

BACKGROUND: Rotational knee movement after reconstruction of the anterior cruciate ligament has been difficult to quantify. The purpose of this study was to identify in vivo whether a more horizontal placement of the femoral tunnel (in the ten o'clock position rather than in the eleven o'clock position) can restore rotational kinematics, during highly demanding dynamic activities, in a knee in which a bone-patellar tendon-bone graft had been used to reconstruct the anterior cruciate ligament. METHODS: We evaluated ten patients in whom a bone-patellar tendon-bone graft had been used to reconstruct the anterior cruciate ligament with the femoral tunnel in the eleven o'clock position, ten patients who had had the same procedure with the femoral tunnel in the ten o'clock position, and ten healthy controls. Kinematic data were collected while the subjects (1) descended from a stairway, made foot contact, and then pivoted 90 degrees on the landing lower limb and (2) jumped from a platform, landed with both feet on the ground, and pivoted 90 degrees on the right or left lower limb. The dependent variable that we examined was tibial rotation during pivoting. RESULTS: The results demonstrated that reconstruction of the anterior cruciate ligament with the femoral tunnel in either the ten or the eleven o'clock position successfully restored anterior tibial translation. However, both techniques resulted in tibial rotation values, during the dynamic activities evaluated, that were significantly larger than those in the intact contralateral lower limbs and those in the healthy controls. Tibial rotation did not differ significantly between the two reconstruction groups or between the healthy controls and the intact contralateral lower limbs. However, we noticed that positioning the tunnel at ten o'clock resulted in slightly decreased rotation values that may have clinical relevance but not statistical significance. CONCLUSIONS: Regardless of which of the two tested positions was utilized to fix the graft to the femur, reconstruction of the anterior cruciate ligament did not restore normal tibial rotation during dynamic activities.