Unintentionally intentional: unintended effects of spinal stimulation as a platform for multi-modal neurorehabilitation after spinal cord injury.

Electrical stimulation of spinal neurons has emerged as a valuable tool to enhance rehabilitation after spinal cord injury. In separate parameterizations, it has shown promise for improving voluntary movement, reducing symptoms of autonomic dysreflexia, improving functions mediated by muscles of the pelvic floor (e.g., bowel, bladder, and sexual function), reducing spasms and spasticity, and decreasing neuropathic pain, among others. This diverse set of actions is related both to the density of sensorimotor neural networks in the spinal cord and to the intrinsic ability of electrical stimulation to modulate neural transmission in multiple spinal networks simultaneously. It also suggests that certain spinal stimulation parameterizations may be capable of providing multi-modal therapeutic benefits, which would directly address the complex, multi-faceted rehabilitation goals of people living with spinal cord injury. This review is intended to identify and characterize reports of spinal stimulation-based therapies specifically designed to provide multi-modal benefits and those that report relevant unintended effects of spinal stimulation paradigms parameterized to enhance a single consequence of spinal cord injury.

Neural population dynamics reveal that motor-targeted intraspinal microstimulation preferentially depresses nociceptive transmission in spinal cord injury-related neuropathic pain.

The purpose of this study is to determine whether intraspinal microstimulation (ISMS) intended to enhance voluntary motor output after spinal cord injury (SCI) modulates neural population-level spinal responsiveness to nociceptive sensory feedback. The study was conducted in vivo in three cohorts of rats: neurologically intact, chronic SCI without behavioral signs of neuropathic pain, and chronic SCI with SCI-related neuropathic pain (SCI-NP). Nociceptive sensory feedback was induced by application of graded mechanical pressure to the plantar surface of the hindpaw before, during, and after periods of sub-motor threshold ISMS delivered within the motor pools of the L5 spinal segment. Neural population-level responsiveness to nociceptive feedback was recorded throughout the dorso-ventral extent of the L5 spinal segment using dense multi-channel microelectrode arrays. Whereas motor-targeted ISMS reduced nociceptive transmission across electrodes in neurologically intact animals both during and following stimulation, it was not associated with altered nociceptive transmission in rats with SCI that lacked behavioral signs of neuropathic pain. Surprisingly, nociceptive transmission was reduced both during and following motor-targeted ISMS in rats with SCI-NP, and to an extent comparable to that of neurologically intact animals. The mechanisms underlying the differential anti-nociceptive effects of motor-targeted ISMS are unclear, although they may be related to differences in the intrinsic active membrane properties of spinal neurons across the cohorts. Nevertheless, the results of this study support the notion that it may be possible to purposefully engineer spinal stimulation-based therapies that afford multi-modal rehabilitation benefits, and specifically that it may be possible to do so for the individuals most in need - i.e., those with SCI-related movement impairments and SCI-NP.

Precision neuromodulation: Promises and challenges of spinal stimulation for multi-modal rehabilitation.

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar presentations when developing spinal stimulation-based therapies. We also motivate advancement of multi-modal rehabilitation paradigms, which leverage the dense interconnectivity of sensorimotor spinal networks and the unique ability of electrical stimulation to modulate these networks to facilitate and guide simultaneous rehabilitation across domains.

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury.

Electrical stimulation of spinal networks below a spinal cord injury (SCI) is a promising approach to restore functions compromised by inadequate excitatory neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared motor pathways and spinal motor networks rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by SCI. Debilitating spasms, spasticity, and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. But whereas spasms and spasticity can often be managed pharmacologically, SCI-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from etiologies other than SCI, and it has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for motor rehabilitation. Thus, we reasoned that spinal stimulation intended to increase transmission in motor pathways may simultaneously reduce transmission in spinal pain pathways. Using a well-validated pre-clinical model of SCI that results in severe bilateral motor impairments and SCI-related neuropathic pain, we show that the responsiveness of neurons integral to the development and persistence of the neuropathic pain state can be enduringly reduced by motor-targeted spinal stimulation while preserving spinal responses to non-pain-related sensory feedback. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with SCI.

Spinal stimulation for motor rehabilitation immediately modulates nociceptive transmission.

Objective. Spinal cord injury (SCI) often results in debilitating movement impairments and neuropathic pain. Electrical stimulation of spinal neurons holds considerable promise both for enhancing neural transmission in weakened motor pathways and for reducing neural transmission in overactive nociceptive pathways. However, spinal stimulation paradigms currently under development for individuals living with SCI continue overwhelmingly to be developed in the context of motor rehabilitation alone. The objective of this study is to test the hypothesis that motor-targeted spinal stimulation simultaneously modulates spinal nociceptive transmission.Approach. We characterized the neuromodulatory actions of motor-targeted intraspinal microstimulation (ISMS) on the firing dynamics of large populations of discrete nociceptive specific and wide dynamic range (WDR) neurons. Neurons were accessed via dense microelectrode arrays implantedin vivointo lumbar enlargement of rats. Nociceptive and non-nociceptive cutaneous transmission was induced before, during, and after ISMS by mechanically probing the L5 dermatome.Main results. Our primary findings are that (a) sub-motor threshold ISMS delivered to spinal motor pools immediately modulates concurrent nociceptive transmission; (b) the magnitude of anti-nociceptive effects increases with longer durations of ISMS, including robust carryover effects; (c) the majority of all identified nociceptive-specific and WDR neurons exhibit firing rate reductions after only 10 min of ISMS; and (d) ISMS does not increase spinal responsiveness to non-nociceptive cutaneous transmission. These results lead to the conclusion that ISMS parameterized to enhance motor output results in an overall net decrease n spinal nociceptive transmission.Significance. These results suggest that ISMS may hold translational potential for neuropathic pain-related applications and that it may be uniquely suited to delivering multi-modal therapeutic benefits for individuals living with SCI.

Per-Anal Endoscopic Myotomy as Rescue Therapy for Hirschsprung Disease After Unsuccessful Surgical Myectomy.

Hirschsprung disease (HD) may affect short, ultrashort, or long segments of the rectum. Invasive endoscopy has gained popularity in its treatment. We report a case of a 9-year-old girl diagnosed with HD at 4-year-old, at which time she underwent a myectomy. Nonetheless, because of the persistence of clinical symptoms such as bowel movements every 5-7 days and abdominal distension, per-anal endoscopic myotomy was recommended. An anterograde myotomy in the posterior wall was performed to the circular layer of the muscularis propria. At the 3-year follow-up, she has continued daily bowel movements without laxatives.

Spontaneous Multimodal Neural Transmission Suggests That Adult Spinal Networks Maintain an Intrinsic State of Readiness to Execute Sensorimotor Behaviors.

Spontaneous action potential discharge (spAP) is both ubiquitous and functionally relevant during neural development. spAP remains a prominent feature of supraspinal networks in maturity, even during unconsciousness. Evidence suggests that spAP persists in mature spinal networks during wakefulness, and one function of spAP in this context could be maintenance of a "ready state" to execute behaviors. The extent to which spAP persists in mature spinal networks during unconsciousness remains unclear, and its function(s), if any, are likewise unresolved. Here, we attempt to reconcile some of the questions and contradictions that emerge from the disintegrated picture of adult spinal spAP currently available. We recorded simultaneously from large populations of spinal interneurons in vivo in male rats, characterizing the spatial distribution of spAP in the lumbar enlargement and identifying subgroups of spontaneously active neurons. We find (1) concurrent spAP throughout the dorsoventral extent of the gray matter, with a diverse yet strikingly consistent mixture of neuron types across laminae; (2) the proportion of neurons exhibiting spAP in deeper, sensorimotor integrative regions is comparable to that in more superficial, sensory-dominant regions; (3) firing rate, but not spike train variability, varies systematically with region; and (4) spAP includes multimodal neural transmission consistent with executing a spinally-mediated behavior. These findings suggest that adult spAP may continue to support a state of readiness to execute sensorimotor behaviors even during unconsciousness. Such functionality has implications for our understanding of how perception is translated into action, of experience-dependent modification of behavior, and (mal)adaptative responses to injury or disease.SIGNIFICANCE STATEMENT Neurons often discharge action potentials (APs) seemingly spontaneously, that is, in the absence of ongoing behaviors or overt stimuli. This phenomenon is particularly evident during neural development, where spontaneous AP discharge (spAP) is ubiquitous in the central nervous system and is crucial to establishing connectivity among functionally related groups of neurons. The function(s) of spAP in adult spinal networks, if any, have remained enigmatic, especially during unconsciousness. Here, we report evidence that one such function could be to support an intrinsic state of readiness to execute sensorimotor behaviors. This finding has implications for our understanding of how perception is translated into action, of experience-dependent modification of behavior, and (mal)adaptative responses to injury or disease.

Spontaneous neural synchrony links intrinsic spinal sensory and motor networks during unconsciousness.

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al., 2014 used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection latencies compatible with mono- and disynaptic interactions and putative excitatory and inhibitory connections. The observed activity is consistent with the hypothesis that salient, experience-dependent patterns of neural transmission introduced during behavior or by injury/disease are reactivated during unconsciousness. Such a spinal replay mechanism could shape circuit-level connectivity and ultimately behavior.

Neumonía adquirida en la comunidad en un hospital terciario español: ¿cómo se comporta en pacientes provenientes de residencia? / Community acquired pneumonia in a Spanish tertiary hospital: how does it work in patients from residence?

No disponible

Qualitative and quantitative evaluation of the use of Twitter as a tool of antimicrobial stewardship.

INTRODUCTION: Social media networks have transformed the sources of information, including health information. In particular, the microblogging service Twitter has been used as a learning tool in the field of medicine as well as a tool for disease surveillance and outbreak management. As antimicrobial resistance is one of the biggest concerns of public health, we aimed to review how Twitter is being used as a tool for antimicrobial stewardship (AMS). METHODS: We used the software Kampal Social® to collect, analyze and monitor tweets from the whole Twitter network to assess the activity that takes place about antibiotics. The study was carried out in three phases: data acquisition, during which we collected data over a six-month period (from 21 September 2016 to 8 February 2017) by monitoring selected users, hashtags and keywords that we knew to be related to AMS; data cleansing, which involved identifying users who were not related to the topic, thus creating a new collection process to remove those users and add newly discovered ones; and, finally, data acquisition and analysis (From 1 April 2017 to 7 March 2018), during which we collected data using the new users obtained in the cleansing phase. We qualitatively characterized the most influential users, we analysed the use of hashtags and the flow of information (the most retweeted users and the global network formed by all the users). RESULTS: Using the tool Kampal Social®, and after a cleansing phase to remove irrelevant information, we worked with a dataset of 1,765,388 tweets. Studying the qualitative characterization of the top-ten influencers, we found that most of them are institutional users, but individual users, such as physicians, and an important medical journal also appeared. Regarding hashtags, '#antibiotics' was the one with the most occurrences. Hashtags follow a regular distribution over time, with some defined peaks connected to important dates and reports about antibiotics. As for the flow of information, we obtained a rather dense network of interconnections formed by all the users who had sent a message, which means that a strong relation exists between the different organizations, professionals and users in general. CONCLUSIONS: Institutions, medical journals, physicians and pharmacists are key opinion leaders in the topic of antibiotics, so they must incorporate social media into their communication strategy to spread the AMS message. More evidence is needed regarding the optimal method of communication to spread information throughout the general population. The development of tools capable of collecting and querying large amounts of Twitter data helped us to assess the impact of antibiotic awareness campaigns and to gain an idea of how Twitter is being used to spread the message about AMS.

Colorectal cancer in young African Americans: clinical characteristics and presentations.

PURPOSE: Colorectal cancer (CRC) is the third most common cancer in the USA, and the incidence in young adults has been increasing over the past decade. We studied the clinical characteristics and presentations of CRC in young African American (AA) adults because available data on how age and ethnicity influence its pattern of presentation is limited. PATIENTS AND METHODS: We conducted a retrospective study of 109 young adults (75 African Americans) below 50 years, who were diagnosed with CRC between 1 January 1997 and 31 December 2016. Proximal CRC was defined as lesions proximal to the splenic flexure. Independent t-tests and χ-test or Fisher's exact test were performed where appropriate to determine the differences between AA and non-AA patients. RESULTS: The mean age at diagnosis was 42 years (range: 20-49 years). Compared with non-AAs, AAs had more frequent proximal CRC (38.7 vs. 14.7%, P=0.003), lower hemoglobin (10.5 vs. 12.7 g/dl, P<0.001), and more frequent weight loss (21.3 vs. 2.9% P=0.014). Non-AAs presented more frequently with rectal bleeding (52.9 vs. 32.0% P=0.037). There was no statistically significant difference in histology, stage, grade, tumor size, and carcinoembryonic antigen level between groups. When we stratified between proximal and distal disease among patients with CRC, we found larger tumor size in distal disease, which presented more with rectal bleeding and bowel habit changes. Proximal disease presented more as abdominal pain and weight loss. CONCLUSION: There should be a higher index of suspicion for CRC in young AA adults presenting with anemia, abdominal pain, and weight loss. Early screening colonoscopy should be advocated in AAs because of the predominance of proximal disease.

Preoperative elective transjugular intrahepatic portosystemic shunt for cirrhotic patients undergoing abdominal surgery.

Despite improvements in the surgical techniques, anesthesia and intensive care, abdominal surgery in patients with cirrhosis remains a challenge. Transjugular intrahepatic portosystemic shunt (TIPS) has been used to manage complications of portal hypertension. Preoperative TIPS (prophylactic) can theoretically improve outcomes in this population. Seven original studies were identified with 24 patients who underwent prophylactic TIPS before abdominal surgery. No perioperative mortality or major abdominal bleeding attributable to portal hypertension was reported for this cohort. One patient had poor wound healing post surgery (4.2%), one had right heart failure (4.2%), and five developed hepatic encephalopathy (20.8%) post surgery. More evidence is needed to optimize the timing of surgery post TIPS and the selection of an appropriate stent size to further decrease the associated morbidity. Overall, the decision for prophylactic TIPS placement for cirrhotic patients undergoing abdominal surgery needs individualization to allow its safe use with concomitant improvement in perioperative morbidity.

Incorporación del farmacéutico de hospital al proyecto 'Compromiso por la calidad de las Sociedades Científicas en España' / Incorporation of the hospital pharmacist into the project 'Commitment to quality of the Spanish scientific societies'

No disponible

Conciliación de la medicación: una responsabilidad compartida / Medication reconciliation: a shared responsibility

No disponible

Asistencia a la gestante con diabetes. Guía de práctica clínica actualizada en 2014 / Care of pregnancies complicated by diabetes. Clinical practice guidelines: 2014 update

La diabetes es una de las complicaciones metabólicas más frecuentes de la gestación y se asocia a un incremento del riesgo de morbimortalidad maternal y fetal, que pueden evitarse y/o reducirse con un adecuado control. En la diabetes pregestacional, la preparación específica previa a la gestación es indispensable para intentar conseguir un control glucémico lo más próximo a la normalidad, evaluar complicaciones y revisar las pautas de tratamientos farmacológicos. En el caso de la diabetes gestacional, el tratamiento de esta entidad ha demostrado disminuir la tasa de complicaciones maternas y perinatales, por lo que su diagnóstico está justificado. En relación con la estrategia diagnóstica, ante la falta de consenso y la controversia desatada tras la aparición de los nuevos criterios IADPSG, el grupo ha decidido mantener la misma estrategia diagnóstica en 2 pasos y con los mismos puntos de corte hasta disponer de datos sólidos que avalen la introducción de nuevos criterios

Diabetes is one of the most common metabolic complications of pregnancy, and is associated with an increased risk of maternal and foetal morbidity and mortality that can be prevented and/or reduced with adequate glycaemic control. In pre-gestational diabetes, specific preparation prior to the pregnancy is essential in order to achieve glycaemic control near to normal as possible and to evaluate complications and review pharmacologic treatment prescription. The treatment of gestational diabetes has been shown to decrease the rate of maternal and perinatal complications, thus its diagnosis is justified. As regards the diagnostic strategy and due to the lack of consensus and the controversy arising after the publication of the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG), the group has decided to keep the same diagnostic strategy in two stages, and with the same cut-off points, until there are solid data available that support the introduction of new criteria

Pharmacist-led medication reconciliation to reduce discrepancies in transitions of care in Spain.

BACKGROUND: Medication errors are one of the main causes of morbidity amongst hospital inpatients. More than half of medication errors occur at 'interfaces of care', when patients are discharged or transferred to the care of another physician. Medication reconciliation is the process of reviewing patients' complete previous medication regimen, comparing it with current prescriptions, and analysing and resolving any discrepancies that the pharmacist does not believe to be intentional (unjustified discrepancies). OBJECTIVE: To quantify and analyse reconciliation unjustified discrepancies detected by a pharmacist in patients admitted to an internal medicine unit (IMU) over a 3-year period. SETTING AND METHOD: The hospital employs a pharmacist who acts as a link between the primary care services and the internal medicine specialist care unit. A retrospective descriptive study on the reconciliation discrepancies found was carried out. Medication reconciliation was performed upon admission in all patients transferred from the Accident and Emergency department (A&E) and admitted to the IMU, and also at the time of discharge. The interventions were categorised based on the consensus document on terminology and medication classification published by the Spanish Society of Hospital Pharmacy. MAIN OUTCOME MEASURE: Number of patients with unjustified discrepancies, also known as reconciliation errors. RESULTS: 2,473 patients had their treatment reviewed at the time of admission and 1,150 at discharge. 866 reconciliation discrepancies were detected in 446 patients (1.94 per patient). 807 (93 %) were accepted by the prescribing physician and classified as reconciliation errors. 16.8 % of patients had at least one reconciliation error: 63.8 % of these errors were incomplete prescriptions, 16.6 % were medication omissions and 10.5 % were errors in dosage, administration method and/or frequency. CONCLUSION: The rate of medication errors found in this study is low compared with other similar studies. The most common error was "incomplete prescriptions", most of them generated by the Accident and Emergency department. A computerised clinical history would help to decrease the number of reconciliation errors. Pharmacist interventions focused on medication reconciliation are well accepted by physicians, improving the quality of clinical histories and decreasing the number of medication errors that occur across transitions in patient care.