Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Surgical management of complex ileocolonic Crohn's disease: a survey of IBD colorectal surgeons to assess variability in operative strategy.

INTRODUCTION: To explore the reported variability in the surgical management of ileocolonic Crohn' s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn's disease. METHODS: Anonymous videos demonstrating the small bowel walkthrough and anonymised patients' clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. RESULTS: Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. CONCLUSIONS: The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy.

Video-laparoscopic assessment of the small bowel in Crohn's disease: a comparative study to evaluate surgeons' inter-observer variability.

BACKGROUND: Assessment of the entire small bowel is advocated during Crohn's disease (CD) surgery, as intraoperative detection of new lesions may lead to change in the planned procedure. The aim of this study was to evaluate the inter-observer variability in the assessment of extent and severity of CD at the small bowel laparoscopic "walkthrough". METHODS: A survey on laparoscopic assessment of the small bowel in patients with CD, including items adapted from the MREnterography or ultrasound in Crohn's disease (METRIC) study and from the classification of severity of mesenteric disease was developed by an invited committee of colorectal surgeons. Anonymous laparoscopic videos demonstrating the small bowel "walkthrough" in ileocolonic resection for primary and recurrent CD were distributed to the committee members together with the anonymous survey. The primary outcome was the rate of inter-observer variability on assessment of strictures, dilatations, complications and severity of mesenteric inflammation. RESULTS: 12 assessors completed the survey on 8 small bowel walkthrough videos. The evaluation of the small bowel thickening and of the mesenteric fat wrapping were the most reliable assessments with an overall agreement of 87.1% (k = 0.31; 95% CI - 0.22, 0.84) and 82.7% (k = 0.35; 95% CI - 0.04, 0.73), respectively. The presence of strictures and pre-stenotic dilatation demonstrated agreement of 75.2% (k = 0.06: 95% CI - 0.33, 0.45) and 71.2% (k = 0.33; 95% CI 0.15, 0.51), respectively. Evaluation of fistulae had an overall agreement of 75.3%, while there was a significant variation in the evaluation of mild, moderate and severe mesenteric disease with overall agreement ranging from 33.3 to 100%. CONCLUSION: Laparoscopic assessment of the small bowel thickening and of the presence of mesenteric fat wrapping is reliable for the intraoperative evaluation of CD with high inter-rater agreement. There is significant heterogeneity in the assessment of the severity of the mesenteric disease involvement.

Transport, mechanical and global migration data of multilayer copolyamide nanocomposite films with different layouts.

Transport, mechanical and global migration data concern multilayer food packaging films with different layouts, all incorporating a layered silicate/polyamide nanocomposite as oxygen barrier layer, and a low-density polyethylene (LDPE) as moisture resistant layer in direct contact with food. The data are related to "Tuning of co-extrusion processing conditions and film layout to optimize the performances of PA/PE multilayer nanocomposite films for food packaging" by Garofalo et al. (2017) [1]. Nanocomposite multilayer films, with different relative layer thicknesses and clay types, were produced using a laboratory scale co-extrusion blown-film equipment and were analyzed in terms of transport to oxygen and water vapor, mechanical properties and overall migration. The results have shown that all the multilayer hybrid films, based on the copolyamide layer filled with Cloisite 30B, displayed the most significant oxygen barrier improvements and the best mechanical properties compared to the unfilled films. No significant alteration of the overall migration values was observed, as expectable [2], [3], [4]. The performance improvement was more relevant in the case of the film with the thinner nanocomposite layer.

Collagen and matrix metalloproteinase-2 and -9 in the ewe cervix during the estrous cycle.

The cervical collagen remodeling during the estrous cycle of the ewe was examined. The collagen concentration determined by a hydroxyproline assay and the area occupied by collagen fibers (%C), determined by van Gieson staining, were assessed in the cranial and caudal cervix of Corriedale ewes on Days 1 (n = 6), 6 (n = 5), or 13 (n = 6) after estrous detection (defined as Day 0). In addition, the gelatinase activity by in situ and SDS-PAGE gelatin zymographies and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9, respectively) expression by immunohistochemistry were determined. The collagen concentration and %C were lowest on Day 1 of the estrous cycle (P < 0.04), when MMP-2 activity was highest (P < 0.006) and the ratio of activated to latent MMP-2 trend to be highest (P = 0.0819). The MMP-2 activity was detected in 73% of the homogenized cervical samples, and its expression was mainly detected in active fibroblasts. By contrast, the MMP-9 activity was detected in 9% of the samples, and its scarce expression was associated with plasmocytes, macrophages, and lymphocytes. Matrix metalloproteinase-2 expression was maximal on Day 1 in the cranial cervix and on Day 13 in the caudal cervix and was lower in the cranial than in the caudal cervix (P < 0.0001). This time-dependent increase in MMP-2 expression that differed between the cranial and caudal cervix may reflect their different physiological roles. The decrease in the collagen content and increase in fibroblast MMP-2 activity in sheep cervix on Day 1 of the estrous cycle suggests that cervical dilation at estrus is due to the occurrence of collagen fiber degradation modulated by changes in periovulatory hormone levels.

Cervical changes in estrogen receptor alpha, oxytocin receptor, LH receptor, and cyclooxygenase-2 depending on the histologic compartment, longitudinal axis, and day of the ovine estrous cycle.

The aim was to investigate the histologic distribution of estrogen receptor α (ERα), oxytocin receptor (OxR), LH receptor (LHR), and cyclooxygenase-2 (COX-2) in the cervix of the ewe during the estrous cycle. Immunohistochemistry was performed in the cranial and caudal cervix of Corriedale ewes on Day 1 (n = 6), 6 (n = 5), or 13 (n = 6) after estrous detection (Day 0). The ERα proportional score (%ERα nuclei) was lower in the cranial cervix than in the caudal cervix, whereas the OxR and COX-2 immunostaining areas (%areas) were greater in the cranial cervix than in the caudal cervix (P < 0.04). The %ERα nuclei decreased from Days 1 to 13 in luminal epithelia, but increased from Days 1 to 6 or remained unchanged in stromata (P < 0.003). The %OxR area was higher on Day 6 than on Days 1 and 13 in the superficial glandular epithelium, and increased from Days 1 to 13 in the deep glandular epithelium (P < 0.04). The %LHR area increased during the estrous cycle in luminal epithelia and fold stroma (P < 0.004). The %COX-2 area was restricted to epithelia, and it was lower on Day 1 than on Days 6 and 13 in luminal epithelia (P < 0.05). Differences in ERα, OxR, LHR, and COX-2 between cranial and caudal cervical zones indicate different physiological functions, and their cyclic variations in the cervical epithelia, in contrast to little or no variations in the stroma, suggest a hormone-responsive driving role of epithelia in cervical function.

[Assessment of congenital malformation risk in the progeny of the military and civilian personnel of the Salto di Quirra military base: preliminary results]. / Valutazione del rischio di malformazioni congenite nella progenie del personale militare e civile del Poligono Interforze del salto di Quirra: risultati preliminari.

INTRODUCTION: We evaluated the congenital malformation rate in the progeny of the personnel of the Salto di Quirra military base in Sardinia. METHODS: During 2011, we gathered questionnaire information on the reproductive history of 389 employees, more then 99% of those eligible for routine health surveillance. RESULTS: the observed congenital malformation rate (20.1 x 10(-3), 95% CI 6.3 - 33.8) was lower than that reported by the Italian Registries of Congenital Malformations, and it did not vary by exposure to radiofrequency, elf electromagnetic fields, and solvents, and by jobs associated with alleged exposure to nanoparticles or alpha radiation. CONCLUSIONS: Our findings suggest that the documented or alleged occupational exposures among the PISQ workforce did not increase the congenital malformation rate in the progeny.

Expression of genes for oestrogen and progesterone receptors in the cervix of anoestrous ewes treated with gonadotrophin releasing hormone with or without progesterone priming.

The aim was to determine the oestrogens receptor alpha (ERα) mRNA and the binding capacity of oestrogens (ER) and progesterone receptor (PR) in the cervix of anoestrous ewes treated with gonadotrophin-releasing hormone (GnRH) with or without progesterone (P) priming, at the expected time of induced ovulation and early luteal phase. In Experiment 1, ewes were treated with P for 10 days (n=4), with nine micro-doses of GnRH followed by a GnRH bolus injection (n=4), or with P plus GnRH treatments (n=3), and tissues were harvested either without treatment (n=4), when P was removed, or 24h after the GnRH bolus injection. In Experiment 2, ewes were treated with the same GnRH or P plus GnRH treatments and tissues were harvested on Day 1 (n=12) or Day 5 (n=10) after the GnRH bolus injection. In the cranial cervix, the P treatment decreased and the GnRH treatment (after P treatment) increased the ERα mRNA, ER and PR concentrations (P<0.002). The ERα mRNA and ER concentrations were greater on Day 1, than on Day 5 in P plus GnRH treated ewes (P<0.0005). In the caudal cervix, lesser ERα mRNA, ER and PR concentrations than cranial cervix were found (P<0.0001). In conclusion, the ERα transcriptional activity and ER and PR binding capacity were strongly influenced by P and/or GnRH treatments in the cranial cervix, while the steroid receptors binding capacity remained unchanged in the caudal cervix of anoestrous ewes at the expected time of induced ovulation and early luteal phase.

Oestrogen and progesterone receptor binding capacity and oestrogen receptor alpha expression (ERalpha mRNA) along the cervix of cycling ewes.

The aim of the present work was to study the oestrogen receptor (ER) and progesterone receptor (PR) binding capacity and the oestrogen receptor alpha (ERalpha) mRNA concentration in cranial and caudal cervix during the ovine oestrous cycle. Cervical samples of synchronised Corriedale ewes were obtained on Day 1 (n=7), 6 (n=6) or 13 (n=7) after oestrus detection (Day 0). The ER and PR binding capacity by ligand-binding assay and the ERalpha mRNA concentration by solution hybridisation in both cranial and caudal zones of the cervix were determined. The ER and PR binding capacity were higher (P<0.005) on Day 1 than on Days 6 and 13 in both cranial and caudal zones. The ERalpha mRNA concentrations were higher (P<0.0001) on Day 1 than on Days 6 and 13 only in the caudal zone. The PR binding capacity and ERalpha mRNA concentration were higher (P<0.005) in the caudal than in the cranial zone on Day 1. The ER and PR expression in the ovine cervix varied during the oestrous cycle in agreement with the known upregulation exerted by oestrogen and downregulation exerted by progesterone. Differences in ER and PR expression along the longitudinal axis of the ovine cervix were found, reflecting histological and functional differences between the cranial and caudal zones.

Complex physiological traits as biomarkers of the sub-lethal toxicological effects of pollutant exposure in fishes.

Complex physiological traits, such as routine aerobic metabolic rate or exercise performance, are indicators of the functional integrity of fish that can reveal sub-lethal toxicological effects of aquatic pollutants. These traits have proved valuable in laboratory investigations of the sub-lethal effects of heavy metals, ammonia and various xenobiotics. It is not known, however, whether they can also function as biomarkers of the complex potential range of effects upon overall functional integrity caused by exposure to mixtures of chemicals in polluted natural environments. The current study used portable swimming respirometers to compare exercise performance and respiratory metabolism of fish exposed in cages for three weeks to either clean or polluted sites on three urban European river systems: the river Lambro, Milan, Italy; the rivers Blythe, Cole and Tame, Birmingham, UK; and the river Amstel, Amsterdam, The Netherlands. The UK and Italian rivers were variously polluted with high levels of both bioavailable heavy metals and organics, and the Amstel by mixtures of bioavailable organics at high concentrations. In both the UK and Italy, indigenous chub (Leuciscus cephalus) exposed to clean or polluted sites swam equally well in an initial performance test, but the chub from polluted sites could not repeat this performance after a brief recovery interval. These animals were unable to raise the metabolic rate and allocate oxygen towards exercise in the second trial, an effect confirmed in successive campaigns in Italy. Swimming performance was therefore a biomarker indicator of pollutant exposure in chub exposed at these sites. Exposure to polluted sites on the river Amstel did not affect the repeat swimming performance of cultured cloned carp (Cyprinus carpio), indicating either a species-specific tolerance or relative absence of heavy metals. However, measurements of oxygen uptake during swimming revealed increased rates of routine aerobic metabolism in both chub and carp at polluted sites in all of the rivers studied, indicating a sub-lethal metabolic loading effect. Therefore, the physiological traits of exercise performance and metabolic rate have potential as biomarkers of the overall sub-lethal toxic effects of exposure to complex mixtures of pollutants in rivers, and may also provide insight into why fish do not colonize some polluted environments.

[The MMPI-2 test in the evaluation of the mobbing syndrome]. / Il test MMPI-2 nella valutazione della sindrome da mobbing.

MMPI-2 test is widely used in psychodiagnostic evaluation as well as in the evaluation of psychic pathologies related to psychosocial adversative events in working activities. A more efficacious use of MMPI-2 test in the working context can be achieved by the individuation of indexes able to facilitate the evaluation of mobbing syndrome. This work is based on the analysis of 150 cases (39.7% women and 60.7% men, 30 to 60 years of age), evaluated through an accurate examination of working history and a series of clinic conversations, followed by psychodiagnostic evaluation. The average of T-scores on the clinical scale, the content scale, the PK addition scale and the validation scale were calculated from tests. Pathologic high T-scores on the scales Hs, D. Hy e Pa were found in subjects having positive mobbing anamnesis. These results strongly indicate the presence of clinical specificities in workers exposed to working harassments, and that these specificities can be efficaciously evidenced by the MMPI-2 test.

Cognition and behavior in children with benign epilepsy with centrotemporal spikes (BECTS).

Characteristics of cognitive deficits in benign childhood epilepsy with centrotemporal spikes (BECTS) remain unclear. The authors screened 200 BECTS children presenting for a clinical trial, finding relative weaknesses in fine motor control, visual learning, and attention in the presence of overall normal intellect, with simple partial seizures associated with more difficulty. Parental concerns for psychosomatic and learning problems were noted. Monitoring select cognitive and behavioral features in BECTS appears appropriate.

Corpus luteum life span and pituitary oestrogen and progesterone receptors in cyclic and gonadotrophin-releasing hormone-treated anoestrous ewes.

The present study investigated the pituitary oestrogen (ER) and progesterone (PR) receptor concentrations in ewes during the oestrous cycle in the breeding season (n = 19), and in anoestrous ewes treated with gonadotrophin-releasing hormone (GnRH) (n = 11) and anoestrous ewes treated with progesterone + GnRH (n = 11). The pituitary ER and PR concentrations at the expected time of ovulation and in the early and late luteal phases were measured by binding assay. The pattern of pituitary ER and PR concentrations in the progesterone + GnRH-treated ewes resembled the pattern found during the normal oestrous cycle, with ER and PR concentrations decreasing from the time of ovulation to the early luteal phase. In contrast, in ewes treated with GnRH alone, ER and PR concentrations increased in the early luteal phase, which may increase the inhibitory effects of steroid hormones on luteinising hormone secretion, ultimately leading to the development of subnormal luteal phases.

Experimentally induced subnormal or normal luteal phases in sheep: reproductive hormone profiles and uterine sex steroid receptor expression.

This study investigated if ewes expected to have subnormal luteal phases (SNLP) present a different pattern of uterine oestrogen receptor (ER) and progesterone receptor (PR) expression at the expected time of premature luteolysis. The concentrations of uterine ER, PR and ERalpha mRNA, and the steroid ovarian hormone were determined in anoestrous ewes treated with either gonadotrophin-releasing hormone (GnRH) to develop a SNLP (n = 16), or progesterone + GnRH to develop a normal luteal phase (NLP; n = 16). The ER, PR and ERalpha mRNA concentrations were measured using binding and solution hybridisation assays, while the hormone level concentration was measured by radioimmunoassay. In all ewes, a luteinising hormone- and follicle-stimulating hormone-synchronised surge was found. The SNLP group had lower preovulatory oestradiol levels than the NLP group. On Day 5, the SNLP group had lower progesterone levels, and higher uterine ER, PR and ERalpha mRNA concentrations than the NLP group. While in the SNLP group the receptor expression increased from Days 1 to 5, in the NLP group the receptor expression decreased. The results suggest that the induction of steroid receptor expression in the uterus and the hormonal environment found in the experimental SNLP group at the expected time of premature luteolysis may be involved in the mechanisms causing SNLP.

Differential estradiol effects on estrogen and progesterone receptors expression in the oviduct and cervix of immature ewes.

In order to study the effect of estradiol-17beta (E2) on estrogen (E) and progesterone (P) receptors expression in oviduct and cervix of lambs, their respective transcripts (ERalpha mRNA and PR mRNA) were determined by solution hybridization and the receptor proteins (ER and PR) by binding assays after E2 treatments. Lambs (n=4 in each group) were not treated or treated with one, two or three i.m. injections of E2 (1 microg/kg) at 24 h of interval. Tissues were obtained 12 or 24 h after the last E2 injection. Estradiol treatments increased ERalpha mRNA and PR mRNA concentrations in an organ-dependent manner: transitory in the oviduct while maintained in the cervix. The E2 effect on the oviductal and cervical ER and PR concentrations were biphasic, with an initial reduction of receptors content that was followed by restoration. The ER restoration in oviduct was earlier than in the cervix. In summary, this study shows that E2 treatments may exert an inductive effect in ERalpha mRNA and PR mRNA levels and a biphasic effect in ER and PR concentrations in oviduct and cervix of immature ewe. These E2 effects varied in timing and strength depending on the organ of the reproductive tract.

Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy. METHODS: A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. Following a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin 600 mg/day administered twice daily (BID) or three times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing > or =50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population. RESULTS: Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID (p < or = 0.0001) and 44% for pregabalin BID (p < or = 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo (p < or = 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia. CONCLUSIONS: Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice daily or three times daily schedule with similar efficacy and tolerability results.

The role of sex steroid receptors in sheep female reproductive physiology.

Cell responsiveness to steroid hormones is related to the number and affinity of its receptors, thus factors affecting steroid expression will influence tissue sensitivity and functionality. The present review discusses the role of oestrogen and progesterone receptors in sheep female reproductive physiology. The mechanism of steroid hormone action in the target cell is introduced first; the tissue distribution, physiological functions and regulation of oestrogen receptor subtypes and progesterone receptor isoforms in ruminants are reported. The role of steroid receptors in target tissues (with emphasis on the uterus and pituitary gland) during different physiological events is addressed in an attempt to clarify oestrogen and progesterone actions in different developmental and reproductive stages: prepubertal period, oestrous cycle, pregnancy, post-partum period and seasonal anoestrus. The present review shows how the distinct reproductive stages are accompanied by dramatic changes in uterine receptor expression. The role of oestrogen and progesterone receptors in the molecular mechanism responsible for premature luteolysis that results in subnormal luteal function is discussed. Finally, the effect of nutrition on sex steroid receptor expression and the involvement on reproductive performance is reported.

Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.

BACKGROUND: Pregabalin is an alpha(2)-delta ligand that has anxiolytic, analgesic, and anticonvulsant properties. OBJECTIVE: To establish the efficacy, safety, and tolerability of pregabalin administered twice-daily (BID) without dose titration as adjunctive treatment in patients with partial seizures and to confirm the dose-response relationship. METHODS: This 76-center, double-blind, randomized, placebo-controlled, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Patients with refractory partial seizures on one to three antiepileptic drugs were randomly assigned to one of five treatment groups (placebo or 50, 150, 300, and 600 mg/d pregabalin, all administered BID). Efficacy was assessed using seizure frequency reduction and responder rate (> or =50% seizure reduction from baseline). Pharmacokinetic parameters were estimated. RESULTS: A total of 453 patients were included in the intent-to-treat analysis. The median baseline seizure rate was 10 per month. Seizure frequency reductions from baseline were 7% (placebo; n = 100), 12% (50 mg/d; n = 88), 34% (150 mg/d; n = 86), 44% (300 mg/d; n = 90), and 54% (600 mg/d; n = 89). Responder rates (> or =50% seizure reduction) were 14% (placebo), 15% (50 mg/d), 31% (150 mg/d), 40% (300 mg/d), and 51% (600 mg/d). Discontinuation rates due to adverse events were 5% (placebo), 7% (50 mg/d), 1% (150 mg/d), 14% (300 mg/d), and 24% (600 mg/d). The 150-, 300-, and 600-mg/d pregabalin groups were associated with greater reductions in seizures (p < or = 0.0001) and greater responder rates compared with the placebo group (p < or = 0.006). There was a favorable dose-response trend for both seizure reductions (p < or = 0.0001) and responder rate (p < or = 0.001). CONCLUSION: Adjunctive therapy with pregabalin 150, 300, and 600 mg/d, given in twice-daily doses without titration, is significantly effective and well tolerated in the treatment of patients with partial seizures as demonstrated in patients with refractory partial seizures.