Optic nerve and macular optical coherence tomography in recovered COVID-19 patients.

PURPOSE: To investigate the peripapillary retinal nerve fiber layer thickness (RNFLT), macular RNFLT, ganglion cell layer (GCL), and inner plexiform layer (IPL) thickness in recovered COVID-19 patients compared to controls. METHODS: Patients previously diagnosed with COVID-19 were included, while healthy patients formed the historic control group. All patients underwent an ophthalmological examination, including macular and optic nerve optical coherence tomography. In the case group, socio-demographic data, medical history, and neurological symptoms were collected. RESULTS: One hundred sixty patients were included; 90 recovered COVID-19 patients and 70 controls. COVID-19 patients presented increases in global RNFLT (mean difference 4.3; CI95% 0.8 to 7.7), nasal superior (mean difference 6.9; CI95% 0.4 to 13.4), and nasal inferior (mean difference 10.2; CI95% 2.4 to 18.1) sectors of peripapillary RNFLT. Macular RNFL showed decreases in COVID-19 patients in volume (mean difference -0.05; CI95% -0.08 to -0.02), superior inner (mean difference -1.4; CI95% -2.5 to -0.4), nasal inner (mean difference -1.1; CI95% -1.8 to -0.3), and nasal outer (mean difference -4.7; CI95% -7.0 to -2.4) quadrants. COVID-19 patients presented increased GCL thickness in volume (mean difference 0.04; CI95% 0.01 to 0.07), superior outer (mean difference 2.1; CI95% 0.8 to 3.3), nasal outer (mean difference 2.5; CI95% 1.1 to 4.0), and inferior outer (mean difference1.2; CI95% 0.1 to 2.4) quadrants. COVID-19 patients with anosmia and ageusia presented an increase in peripapillary RNFLT and macular GCL compared to patients without these symptoms. CONCLUSIONS: SARS-CoV-2 may affect the optic nerve and cause changes in the retinal layers once the infection has resolved.

Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection.

PURPOSE: To describe macular vessel density and perfusion in COVID-19 patients using coherence tomography angiography (OCTA) and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters. METHODS: Cross-sectional analysis conducted at the Hospital Clinico San Carlos in Madrid, Spain. Patients with laboratory-confirmed COVID-19 that were attended in the Emergency Department (ED) from March 23 to March 29, 2020 were included. Fundus examination and OCTA were performed 4 weeks after being attended in ED. Macular OCTA parameters were analyzed and correlated with clinical (severity and hypoxemia- oxygen saturation < 92%) and laboratory parameters during hospital stay (D-Dimer-DD, lactate dehydrogenase-LDH and C-reactive protein-CRP). RESULTS: 80 patients were included, mean age 55(SD9) years old; 46.3% male. We reported macular vessel density and perfusion measurements in COVID-19 patients. Those patients with D-Dimer ≥ 500 ng/ml during SARS-CoV-2 infection had a decrease of central vessel density (mean difference 2.2; 95%CI 0.4-3.9) and perfusion density (mean difference 4.9; 95%CI 0.9-8.9) after the acute phase of COVID-19. These variations of vessel density and perfusion density were not documented in patients with LDH ≥ 500 U/L, CRP ≥ 10 mg/L and hypoxemia. CONCLUSIONS: COVID-19 patients showed short-term retinal vasculature abnormalities which may be related to a prothrombotic state associated with SARS-CoV-2 infection. Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs, further research is needed to establish whether patients with increased D-Dimer levels require more careful assessment and follow-up after COVID-19.

OBJETIVO: Evaluar la densidad vascular (DV) y la perfusión vascular (PV) retiniana en pacientes con COVID-19 mediante una angiografía por tomografía de coherencia óptica (OCTA), e investigar si existe una correlación entre las anomalías vasculares de la retina y los parámetros clínicos y de laboratorio. MÉTODOS: Análisis transversal realizado en el Hospital Clínico San Carlos, Madrid. Se incluyeron pacientes con diagnóstico confirmado de COVID-19 atendidos en el Servicio de Urgencias (SU) del 23 al 29 de marzo del 2020. Se realizó una exploración oftalmológica y OCTA cuatro semanas después de acudir al SU. Se analizaron los parámetros maculares de OCTA y se correlacionaron con parámetros clínicos (gravedad e hipoxemia-saturación de oxígeno < 92%) y de laboratorio durante la estancia hospitalaria (dímero D [DD], lactato deshidrogenasa [LDH] y proteína C reactiva [CRP]. RESULTADOS: Se incluyeron 80 pacientes, edad media 55 (DE nueve) años; 46,3% hombres. Las personas con DD > 500 ng/mL durante la infección por SARS-CoV-2 tuvieron una disminución de la DV central (diferencia de medias 2,2; IC 95% 0,4 a 3,9) y PV central (diferencia de medias 4,9; IC 95% 0,9 a 8,9) después de la fase aguda de COVID-19. Estas variaciones no se documentaron en los pacientes con LDH > = 500 U/L, CRP > = 10 mg/L y con hipoxemia. CONCLUSIONES: Los pacientes con COVID-19 mostraron anomalías de la vasculatura retiniana a corto plazo que pueden estar relacionadas con un estado protrombótico asociado con la infección por SARS-CoV-2. Dado que la microvasculatura de la retina comparte muchas propiedades morfológicas y fisiológicas con la vasculatura de otros órganos vitales, es necesario seguir investigando para determinar si los pacientes con niveles elevados de DD requieren una evaluación y un seguimiento más cuidadoso.

Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection.

PURPOSE: To describe macular vessel density and perfusion in COVID-19 patients using coherence tomography angiography (OCTA) and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters. METHODS: Cross-sectional analysis conducted at the Hospital Clinico San Carlos in Madrid, Spain. Patients with laboratory-confirmed COVID-19 that were attended in the Emergency Department (ED) from March 23 to March 29, 2020 were included. Fundus examination and OCTA were performed 4 weeks after being attended in ED. Macular OCTA parameters were analyzed and correlated with clinical (severity and hypoxemia- oxygen saturation<92%) and laboratory parameters during hospital stay (D-Dimer-DD, lactate dehydrogenase-LDH and C-reactive protein-CRP). RESULTS: 80 patients were included, mean age 55(SD9) years old; 46.3% male. We reported macular vessel density and perfusion measurements in COVID-19 patients. Those patients with D-Dimer≥500ng/ml during SARS-CoV-2 infection had a decrease of central vessel density (mean difference 2.2; 95%CI 0.4-3.9) and perfusion density (mean difference 4.9; 95%CI 0.9-8.9) after the acute phase of COVID-19. These variations of vessel density and perfusion density were not documented in patients with LDH≥500U/L, CRP≥10mg/L and hypoxemia. CONCLUSIONS: COVID-19 patients showed short-term retinal vasculature abnormalities which may be related to a prothrombotic state associated with SARS-CoV-2 infection. Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs, further research is needed to establish whether patients with increased D-Dimer levels require more careful assessment and follow-up after COVID-19.

Fitting success for three multifocal designs: Multicentre randomised trial.

PURPOSE: To determine if the discontinuation of commercially-available simultaneous vision Multifocal Soft Contact Lenses is independent from the multifocal design. To determine causes for discontinuation and psychosocial factors involved. METHODS: Multicentre single-blinded randomised controlled trial with external blinded evaluation for a three months follow-up period for three intervention groups. 150 single-vision soft wearers were randomly assigned a spherical near centred lens (S-CN), distance centred lens (CD) or aspherical near centred lens (A-CN). Cases of discontinuation, anxiety and quality of life were measured at one week and one month. RESULTS: 120 females and 30 males were included with an age range of 40-62 (48.79 ±â€¯5.23). At one month, the S-CN design had a statistically significant higher risk of discontinuation than the other two OR: 6.12 (95%CI 2.5-14.9). Twenty-eight subjects discontinued wearing S-CN at first week (56%), while discontinuation of CD and A-CD were 15 (30%) and 11 (22%), with a statistically significant difference between S-CN design and the other two (p = 0.001). There were not statistically significant differences when direct comparison between discontinuation of CD and A-CN was made (p = 0.36). Thirty-two percent discontinued the use because of poor distance vision and 28% because of both poor distance and near vision. Psychosocial factors were not statistically significant. CONCLUSIONS: Discontinuation of Multifocal Soft Contact Lenses is dependent on the design. Most common cause for discontinuation is poor distance vision. Psychosocial factors do not impact on discontinuation rates.

Role of 3T multiparametric magnetic resonance imaging without endorectal coil in the detection of local recurrent prostate cancer after radical prostatectomy: the radiation oncology point of view.

OBJECTIVE: The aims of this study were to evaluate the role of 3 tesla multiparametric magnetic resonance imaging (3TmMRI) without endorectal coil in the detection of radiographic local recurrences (rLRs) in a contemporary cohort of patients with prostate cancer who presented with biochemical recurrence after radical prostatectomy (RP) with low prostate-specific antigen (PSA) levels, and to identify clinical parameters associated with the 3TmMRI findings. MATERIALS AND METHODS: Between 2009 and 2013, 57 patients with biochemical recurrence of prostate cancer after RP who were considered for salvage radiation therapy (SRT) were included. 3TmMRI with T2-weighted imaging, diffusion weighted imaging (DWI) and dynamic contrast-enhanced imaging without endorectal coil was carried out in all patients before treatment. RESULTS: In 14 out of 57 patients (24.56%) local recurrence was detected through 3TmMRI. Median pre-SRT PSA was 0.40 ng/ml (interquartile range 0.30-2.05 ng/ml). The recurrence was perianastomotic in eight out of 14 patients (57.14%) and retrovesical in six out of 14 patients (42.86%). The median size of the local recurrence was 15.2 mm (range 8.0-46.0 mm). The probability of rLR was significantly higher in patients with PSA levels above 0.5 ng/ml [adjusted odds ratio (OR) 6.25, 95% confidence interval (CI) 1.27-30.79, p = 0.02] or PSA doubling time (PSADT) over 14 months (adjusted OR 7.12, 95% CI 1.40-36.25, p = 0.01). CONCLUSIONS: This is the first study to find a significant relationship between the PSADT and the rLR through MRI. Patients with PSADT longer than 14 months or pre-SRT PSA above 0.5 ng/ml benefited most from 3TmMRI. Its routine use could have significant clinical implications for SRT.

Drug-eluting stent thrombosis in the treatment of chronic total coronary occlusions: incidence, presentation and related factors. Data from the CIBELES trial.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the incidence of drug-eluting stent thrombosis (sirolimus or everolimus) in patients with chronic total coronary occlusions (CTO) and to determine its clinical implications and related factors. METHODS: Data from the 12-month follow-up of the 207 patients included in the CIBELES trial with CTO were analyzed. RESULTS: Stent thrombosis occurred in three patients, two definite and one probable (overall thrombosis rate: 1.4%). However, there were no cases of death or Q-wave myocardial infarction. In univariate analysis, patients with a higher incidence of stent thrombosis were those in whom the target vessel was the left anterior descending, who had single-vessel disease, were assigned to treatment with sirolimus-eluting stents, and those with smaller minimum luminal diameter immediately after the procedure. In multivariate analysis, the only independent predictor of stent thrombosis was minimal luminal diameter immediately after the procedure. CONCLUSIONS: The rate of drug-eluting stent thrombosis in patients with CTO is relatively low (1.4%). The only independent predictor of stent thrombosis in this context was minimal luminal diameter after the procedure and the clinical presentation was in all cases relatively benign.

A comparison of robotic walking therapy and conventional walking therapy in individuals with upper versus lower motor neuron lesions: a randomized controlled trial.

OBJECTIVE: To compare a walking reeducation program with robotic locomotor training plus overground therapy (LKOGT) to conventional overground training (OGT) in individuals with incomplete upper motor neuron (UMN) or lower motor neuron (LMN) injuries having either traumatic or nontraumatic nonprogressive etiology. DESIGN: Randomized open controlled trial with blind evaluation by an independent observer. SETTING: An inpatient spinal cord injury rehabilitation center. PARTICIPANTS: A total of 88 adults within 6 months of spinal cord injury onset (group A, 44 with UMN injury, and group B, 44 with LMN injury) were graded on the American Spinal Injury Association Impairment Scale as C or D. Each of these groups was then randomly allocated to conditions 1 or 2. INTERVENTIONS: Condition 1: Subgroups A1 and B1 were treated with LKOGT for 60 minutes. Condition 2: Subgroups A2 and B2 received 60 minutes of conventional OGT 5 days per week for 8 weeks. Subjects with UMN and LMN were randomized into 2 training groups. MAIN OUTCOME MEASURES: Ten-meter walk test and 6-minute walk test (6MWT). Walking Index for Spinal Cord Injury II, lower extremity motor score (LEMS), and the FIM-Locomotor were secondary outcome measures. RESULTS: By using the LKOGT program compared with OGT, we found significant differences in the 6MWT for groups A1 and B1. LKOGT also provided higher scores than did OGT in secondary outcomes such as the LEMS and the FIM-Locomotor. CONCLUSIONS: Robotic-assisted step training yielded better results in the 6MWT and the LEMS in patients with UMN and LMN.

Techniques and material used in the percutaneous treatment of chronic coronary occlusions. Data from the CIBELES study.

INTRODUCTION: In recent years, various specific techniques and materials have been developed for the treatment of coronary chronic total occlusions (CTO). OBJECTIVE: To evaluate the current situation in the treatment of CTO (techniques and material) in our setting. METHODS: We evaluated data on techniques and material used in the CIBELES (ChronIc coronary occlusion treated By EveroLimus Eluting Stent) trial, a randomized comparison of sirolimus- and everolimus-eluting stents in 207 patients with CTO in 13 centers in Spain and Portugal. RESULTS: A radial approach was used in 23% of patients, and retrograde techniques were used in only 5%. A high number of balloons were used (2.2±0.9 per patient). Microcatheters were used in 33% of patients, and post-dilatation balloons in only 25%. The mean number of stents implanted per patient was 2.1±1.0, with a mean total stent length of 49±24 mm. Other devices and techniques used were: Tornus penetration catheter in 4% of patients, rotational atherectomy in 2%, and cutting balloon in 1%. Intracoronary ultrasound was used in only 6% of patients. In 34% of cases, operators used guidewires that were not specifically for CTO. Considerable variability between centers was detected in the use of different techniques, the highest and lowest variability being observed in the use of intracoronary ultrasound and the use of CTO guidewires, respectively. CONCLUSIONS: In the CIBELES trial, techniques and devices specifically designed for the treatment of CTO were used in a relatively low proportion of patients. Considerable variability between centers was detected.

Randomized comparison of sirolimus-eluting and everolimus-eluting coronary stents in the treatment of total coronary occlusions: results from the chronic coronary occlusion treated by everolimus-eluting stent randomized trial.

BACKGROUND: Patients with coronary total occlusions are at especially high risk for restenosis and new revascularizations. Sirolimus-eluting stents dramatically improved the clinical outcome of this subset of patients in randomized trials, but other drug-eluting stents, mainly the everolimus-eluting stent (currently the most frequently used stent), have not yet been evaluated in patients with coronary total occlusions. The objective was to compare the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent in patients with coronary total occlusions. METHODS AND RESULTS: A total of 207 patients with coronary total occlusions and estimated time since occlusion >2 weeks were randomized to everolimus- or sirolimus-eluting stent. The primary end point was in-stent late loss at 9-month angiographic follow-up (noninferiority trial). Clinical follow-up was performed at 1 and 12 months. In-stent late loss at 9 months was 0.29±0.60 versus 0.13±0.69 mm in patients allocated to sirolimus- and everolimus-eluting stent, respectively. The observed difference in in-stent late loss between both groups was -0.16 mm (95% confidence interval, 0.04 to -0.36 mm; P for noninferiority <0.01). The rate of binary angiographic restenosis was 10.8% and 9.1% in patients allocated to sirolimus- and everolimus-eluting stent, respectively (P=0.709), whereas the rate of vessel reocclusion was 3.2% and 1.1%, respectively (P=0.339). At 12 months, the rate of major adverse events was 15.9% versus 11.1% with sirolimus- and everolimus-eluting stent, respectively (P=0.335), and probable or definitive stent thrombosis occurred in 3.0% and 0.0% of patients, respectively (P=0.075). CONCLUSIONS: In patients with coronary total occlusions, everolimus-eluting stent is as effective as sirolimus-eluting stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00793221.

Lokomat robotic-assisted versus overground training within 3 to 6 months of incomplete spinal cord lesion: randomized controlled trial.

BACKGROUND: About 75% of persons with ASIA (American Spinal Injury Association) Impairment Scale C and D incomplete spinal cord injury (SCI) achieve walking ability. OBJECTIVE: To compare a walking reeducation program using Lokomat with conventional overground training among individuals with incomplete SCI of both traumatic and nontraumatic etiology. METHODS: A total of 80 participants from 3 to 6 months after onset admitted to 1 site for rehabilitation were included in a single-blind randomized clinical trial of 2 parallel groups, with blind evaluation by independent observers. Patients received 40 walking reeducation sessions of equal time using a Lokomat program with overground practice or overground mobility therapy alone. Primary measurements of outcome were walking speed and the Walking Index for Spinal Cord Injury (WISCI II). Secondary outcomes were the 6-minute walk test, locomotor section of the Functional Independence Measure, Lower Extremity Motor Score (LEMS), Ashworth Scale, and Visual Analog Scale for pain. RESULTS: No significant differences were found at entry between treatment groups. Walking speed for Lokomat (0.4m/s [0.6-0.2]) and overground therapy (0.3m/s [0.5-0.2]) groups did not differ. The WISCI II for the Lokomat group (16 [8.5-19]) was better than for overground therapy (9 [8-16]). The 6-minute walk test and LEMS displayed significant differences in favor of Lokomat therapy but were not corrected for multiple comparisons. CONCLUSIONS: Robotic-assisted training was equivalent to conventional walk training in patients with a variety of nonprogressive spinal cord pathologies for walking speed, but the need for orthotics and assistive devices was reduced, perhaps because of greater leg strength in the robotic group.

Differential regional brain responses to induced maternal behavior in rats measured by cytochrome oxidase immunohistochemistry.

Maternal behavior (MB) in rats is expressed under neural control of vomeronasal structures. Some of these regions exert an inhibitory role, such as the accessory olfactory bulb (AOB), while others exert an excitatory role, such as the medial preoptic area (MPOA). In previous studies, using 2-DG as a marker for neuron activity at neuron terminal level, we reported that AOB showed a decrease and MPOA an increase when compared with control rats (non-exposed to pups) during the display of MB. In the present study we used a different indicator of neuronal metabolic activity - cytochrome oxidase (COx) - to assess the activity of the same brain regions in relation to induced MB. The induced-MB females showed increased COx expression in the MPOA and reduced COx activity in the AOB in comparison with the control, non-MB group, consistent with our previous findings using 2-DG. Present results provide further evidence of a facilitatory role of MPOA and an inhibitory role of AOB in MB induction.

Identifying patients with chronic low back pain likely to benefit from lumbar facet radiofrequency denervation: a prospective study.

STUDY DESIGN: Case series. Prospective study. OBJECTIVE: This is a prospective study of a group of patients with chronic low back facet joint pain, meticulously selected using a combination of clinical history, examination, imaging tests, and lumbar facet joint block with a local anesthetic, aimed at assessing the efficacy of treatment with percutaneous rhizolysis in reducing pain and improving related disability. SUMMARY OF BACKGROUND DATA: Percutaneous radiofrequency facet joint denervation (rhizolysis) provides significant alleviation of pain and functional disability in patients with chronic low back pain of facet joint origin. However, accurate patient selection represents a clinical challenge. Patient selection based only on the result of diagnostic blocks may lead to disappointing results as the false-positive rate of the anesthetic diagnostic blocks is reported to be more than 30%. METHODS: A total of 86 patients (mean age, 49.87; mean duration of pain, 7.12 y) finally selected for treatment with rhizolysis were those who presented with chronic lumbar pain and a clinical history and examination with characteristics specific to facet joint pain; whose imaging tests ruled out a possible origin of pain other than the facet joints; and who finally responded favorably to facet joint block with a local lumbar anesthetic. All patients were clinically evaluated according to the indications of the Spanish Society for the Study of Diseases of the Spine (GEER). A follow-up of a minimum of 1 year was conducted. RESULTS: After rhizolysis, lumbar pain, measured by the visual analog scale and the Oswestry Low Back Pain Disability Questionnaire, improved significantly (P<0.05), with the reduction in disability due to lumbar pain being reflected in a notable improvement in the patients' quality of life. A total of 89% of patients experienced significant relief from pain after rhizolysis, with this relief lasting 6 months or more in 66%, and a minimum of 1 year in 50% of cases. At 1 year, 75.67% of patients stated that they would willingly undergo the same treatment again. CONCLUSIONS: Rhizolysis is a valuable tool for the symptomatic treatment of chronic lumbar facet joint pain. A meticulous selection of patients using a combination of clinical history, examination, imaging tests, and lumbar facet joint block with a local anesthetic, achieves long-lasting results by helping reduce the impact on these patients' daily activities.

Systematic review and meta-analysis of cannabis treatment for chronic pain.

SETTING: Cannabis preparations have been used as a remedy for thousands of years in traditional medicine. Clinical use of cannabinoid substances is restricted, due to legal and ethical reasons, as well as limited evidence showing benefits. OBJECTIVE: To assess the efficacy and harms of cannabis preparations in the treatment of chronic pain. DESIGN: Systematic review and meta-analysis of double-blind randomized controlled trials that compared any cannabis preparation to placebo among subjects with chronic pain. An electronic search was made in Medline/Pubmed, Embase, and The Cochrane Controlled Trials Register (TRIALS CENTRAL) of all literature published until February 2008, as well as specific web pages devoted to cannabis. Studies were cross-checked, selected, and assessed. RESULTS: Eighteen trials were included. The efficacy analysis (visual analog scales) displayed a difference in standardized means in favor of the cannabis arm of -0.61 (-0.84 to -0.37), with statistical homogeneity (I(2) = 0.0%; P = 0.50). For the analysis of harms, the following Odds Ratios (OR) and number needed to harm (NNH) were obtained: for events linked to alterations to perception, OR: 4.51 (3.05-6.66), NNH: 7 (6-9); for events affecting motor function, 3.93 (2.83-5.47), NNH: 5 (4-6); for events that altered cognitive function, 4.46 (2.37-8.37), NNH: 8 (6-12). CONCLUSIONS: Currently available evidence suggests that cannabis treatment is moderately efficacious for treatment of chronic pain, but beneficial effects may be partially (or completely) offset by potentially serious harms. More evidence from larger, well-designed trials is needed to clarify the true balance of benefits to harms.

Efficacy of acupuncture for the treatment of fibromyalgia: systematic review and meta-analysis of randomized trials.

OBJECTIVE: The study sought to ascertain the effectiveness of acupuncture as a treatment for fibromyalgia MATERIALS AND METHODS: THE FOLLOWING ELECTRONIC DATABASES WERE SEARCHED: PubMed; The Cochrane Library (CENTRAL); EMBASE; CINAHL; and Pascal Biomed (last date of search: January 2008). We analyzed pain intensity and patient withdrawals prior to termination of the study. A meta-analysis was performed, and a weighted global effect obtained using the inverse of variance. RESULTS: This review covered a total of 6 studies (323 subjects). No statistically significant differences were observed in terms of pain intensity (VAS): 0.02 (-0.24 a 0.28) or withdrawals: RR 0.91 (0.53 a 1.58) CONCLUSION: This systematic review found no evidence of benefit resulting from acupuncture versus placebo, as a treatment for fibromyalgia.

Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials.

No systematic review or meta-analysis using a hard outcome has been conducted on the role of benzodiazepines for generalized anxiety disorder (GAD). The objective of this study was to assess the effectiveness and efficacy of benzodiazepines in the treatment of GAD based on trial drop-out rates. We used a systematic review of randomized controlled trials that compared any of the three best established benzodiazepines (diazepam, Lorazepam and aLprazolam) against placebo. Our primary outcome for effectiveness was withdrawal for any reason. Our secondary outcome tapping efficacy was withdrawal due to lack of efficacy, and that tapping side effects was withdrawals due to adverse events. We included 23 trials. Pooled analysis indicated less risk of treatment discontinuation due to lack of efficacy for benzodiazepines, compared to placebo, relative risk (RR) 0.29 (95% CI 0.18-0.45; p < 0.00001). Nevertheless, pooled analysis showed no conclusive results for risk of all-cause patient discontinuation, RR 0.78 (95% CI 0.62-1.00; p = 0.05). Meta-regression model showed that 74% of the variation in logRR across the studies was explained by year of publication (p <0.001). This systematic review did not find convincing evidence of the short-term effectiveness of the benzodiazepines in the treatment of GAD. On the other hand, for the outcome of efficacy, this review found robust evidence in favour of benzodiazepines. Due to the heterogeneity induced by year of publication, three hypotheses are plausibLe when it comes to being able to account for the differences between efficacy and effectiveness observed in the outcomes (publication bias, quality of the trial literature and a non-differential response to the placebo effect).

Investigación clínica: el punto de partida / Clinical research: the starting point

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