Detecting objective and subjective cognitive effects of electroconvulsive therapy: intensity, duration and test utility in a large clinical sample.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depression but the extent and persistence of cognitive side-effects remain uncertain. It has been reported that there is little evidence that impairments last longer than up to 15 days post-ECT. However, relatively few studies have followed patients for even as long as 1 month post-ECT. Here we report results from a brief cognitive battery given prior to ECT and repeated five times up to 6 months post-ECT. METHOD: In a retrospective case-note study of routinely collected clinical data 126 patients treated with ECT completed two neuropsychological tests [Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination (MMSE)] and two subjective reports of memory function, prior to ECT. Patients were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all patients completed all assessments. RESULTS: Performance relative to pre-ECT baseline was significantly poorer at each post-ECT assessment up to 3 months post-ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score showed improvements relative to baseline from 1 month post-ECT. Mood and subjective memory scores improved following ECT and were correlated with one another, but not with either neuropsychological measure. CONCLUSIONS: The CANTAB SRM task revealed reversible cognitive deficiencies relative to a pre-ECT baseline for at least 3 months following ECT, while MMSE score and patients' subjective reports showed only improvement. Visuospatial memory scores eventually exceeded baseline 6 months post-ECT.

A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.

N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy. An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar. In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance. The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol. The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells. One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature. In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.

Modulation of transmembrane pressure in manufacturing scale tangential flow filtration N-1 perfusion seed culture.

Mammalian cells were grown to high density in a 3,000 L culture using perfusion with hollow fibers operated in a tangential flow filtration mode. The high-density culture was used to inoculate the production stage of a biomanufacturing process. At constant permeate flux operation, increased transmembrane pressures (TMPs) were observed on the final day of the manufacturing batches. Small scale studies suggested that the filters were not irreversibly fouled, but rather exposed to membrane concentration polarization that could be relieved by tangential sweeping of the hollow fibers. Studies were undertaken to analyze parameters that influence the hydrodynamic profile within hollow fibers; including filter area, cell density, recirculation flow rate, and permeate flow rate. Results indicated that permeate flow rate had the greatest influence on modulating TMP. Further evaluation showed a significant decrease in TMP when permeate flow was reduced, and this occurred without any negative effect on cell growth or viability. Hence, a 30% reduction of permeate flow rate was implemented at manufacturing scale. A stable operation was achieved as TMP was successfully reduced by 75% while preserving all critical factors for performance in the perfusion bioreactor.

Acceptability of a wearable hand hygiene device with monitoring capabilities.

Transmisssion of infection within healthcare institutions is a significant threat to patients and staff. One of the most effective means of prevention is good hand hygiene. A research team at Toronto Rehabilitation Institute, Ontario, Canada, developed a wearable hand disinfection system with monitoring capabilities to enhance hand wash frequency. We present the findingsof the first phase of a larger study addressing the hypothesis that an electronic hand hygiene system with monitoring and reminding propertieswill increase hand hygiene compliance. This first phase focused on the acceptability and usability of the wearable electronic hand wash device ina clinical environment. The feedback from healthcare staff to the first prototype has provided evidence for the research team to continue with the development of this technology.

Effect of copper variation in yeast hydrolysate on C-terminal lysine levels of a monoclonal antibody.

The ability to control charge heterogeneity in monoclonal antibodies is important to demonstrate product quality comparability and consistency. This article addresses the control of C-terminal lysine processing through copper supplementation to yeast hydrolysate powder, a raw material used in the cell culture process. Large-scale production of a murine cell line exhibited variation in the C-terminal lysine levels of the monoclonal antibody. Analysis of process data showed that this variation correlated well with shifts in cell lactate metabolism and pH levels of the production culture. Small-scale studies demonstrated sensitivity of the cells to copper, where a single low dose of copper to the culture impacted cell lactate metabolism and C-terminal lysine processing. Subsequent analytical tests indicated that the yeast hydrolysate powder, added to the basal media and nutrient feed in the process, contained varying levels of trace copper across lots. The measured copper concentrations in yeast hydrolysate lots correlated well with the variation in lactate and pH trends and C-terminal lysine levels of the batches in manufacturing. Small-scale studies further demonstrated that copper supplementation to yeast hydrolysate lots with low concentrations of copper can shift the metabolic performance and C-terminal lysine levels of these cultures to match the control, high copper cultures. Hence, a strategy of monitoring, and if necessary supplementing, copper in yeast-hydrolysate powders resulted in the ability to control and ensure product quality consistency. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:463-468, 2017.

Age-related differences in dynamic balance control during stair descent and effect of varying step geometry.

The incidence of stairway falls and related injuries remains persistently high; however, the risk of stair injuries could be reduced through improved stairway design. The current study investigated dynamic balance control during stair descent and the effects of varying the step geometry. Data were collected from 20 healthy young and 20 older adults as they descended three staircases (riser heights of 7, 7.5 and 8 inches (178, 190 and 203 mm, respectively)). At each riser height, the tread run length was varied between 8 and 14 inches (203 mm and 356 mm) in one-inch (25 mm) increments. Kinematic data provided measures of segmental and whole-body dynamic control. Results demonstrated that older adults had greater lateral tilt of the upper body than young adults, but actually had larger margins of stability than the young in the antero-posterior direction as a result of their slower cadence. Nonetheless, for both age groups, the longer run lengths were found to provide the largest margins of stability. In addition, increase in run length and decrease in riser height tended to reduce forward upper body tilt. These results help to explain the underlying biomechanical factors associated with increased risk of falls and the relationship with step geometry. Considering the importance of stair ambulation in maintaining independence and activity in the community, this study highlights the definite need for safer stair design standards to minimize the risk of falls and increase stair safety across the lifespan.

Understanding and measuring powered wheelchair mobility and manoeuvrability. Part I. Reach in confined spaces.

PURPOSE: To determine: (1) what wheelchair manoeuvrability factors are important and (2) the effects of powered wheelchair design on the ability to reach in a confined space. METHOD: The relative importance of five aspects of wheelchair manoeuvrability was determined through a survey of users of wheelchairs (N = 52) and health care professionals and others (N = 89). A single young, non-disabled subject undertook repeated trials of reach distance on to a counter at the end of a corridor whose width could be adjusted by moving Styrofoam walls. RESULTS: Reaching, moving in confined spaces and avoiding collisions were more important than speed and avoiding the need to drive backwards. The rear wheel drive powered wheelchair was found to allow the greatest reach when driving backwards into the space and the wheelchair which moved in a sideways direction allowed greatest reach in the narrowest corridor. CONCLUSIONS: The survey concluded that manoeuvring in small spaces and reaching without collisions were important. The powered wheelchair with sideways capability afforded the greatest reach in confined spaces except when the rear wheel drive chair was driven in backwards. The survey respondents did not place a high priority on avoiding backwards driving but some people find this difficult to do safely.

Consent and the individual detained in custody.

It has been acknowledged that autonomy is one of the prima facie principles in modern medical practice and integral to the interchange between doctor and patient even if that meeting does not fulfil the normal criteria for a consultation. The lead having been taken by other jurisdictions, the General Medical Council, the UK national regulatory body for doctors, has now acknowledged the concept of informed consent that was first espoused in cases such as Rogers v. Whitaker. In regard to the concept of informed consent, there are three pertinent issues that the Forensic Physician should consider in deciding upon the adequacy of this: Did that person have capacity in the eyes of the law? The Forensic Physician may be asked to examine individuals whose age span ranges from the newly born to the elderly and there will be potential conflict of interest between parent and child or elderly people and their carers. Even if adequate information was imparted, did a person under the (significant) influence of alcohol or drugs understand the likely implications that would flow from their decision? Was the individual concerned given appropriate information beforehand--in other words, was the consent truly informed? Was the consent given voluntarily? Voluntariness is probably the most significant ethical worry likely to confront the doctor, particularly when examining an individual for fitness to be detained or fitness to be interviewed, both categories of which make up the main work load in this sub-specialty. The thorny ethical dilemmas faced in this specialty are considered and how the professional standard originally defined in Hunter v Hanley and re-iterated in the Bolam test (with subsequent modification in Bolitho) affect the way in which the clinician deals with the problems is likely to face.

Hand hygiene monitoring technology: a systematic review of efficacy.

Electronic and video monitoring systems (EMS/VMS) may improve hand hygiene by providing feedback, real-time reminders or via the Hawthorne effect. The aim of this systematic review was to assess the efficacy of EMS/VMS in improving hand hygiene or reducing the incidence of healthcare-associated infection (HCAI). Experimental and quasi-experimental studies were included if they measured any hand hygiene outcome and/or HCAI incidence. Of the studies included, seven used system-defined compliance (SDC) (N = 6) or hand hygiene event rate (N = 1) as their outcome. SDC differed for all systems. Most (N = 6) were single ward studies. Two uncontrolled pretest‒post-test studies evaluating EMS that provided voice prompts showed increases in SDC, but risk of bias was high. Two uncontrolled time-series analyses of VMS that provided aggregate feedback demonstrated large, sustained improvement in SDC and were at moderate risk of bias. One non-randomized controlled trial of EMS with aggregate feedback found no difference in hand hygiene frequency but was at high risk of bias. Two studies evaluated EMS providing individual feedback and real-time reminders. A pretest‒post-test study at high risk of bias showed an increase in SDC. An RCT at low risk of bias showed 6.8% higher SDC in the intervention arm partially due to a fall in SDC in the control arm. In conclusion, the overall study quality was poor. The study at lowest risk of bias showed only a small increase in SDC. VMS studies at moderate risk of bias showed rapid and sustained increases in SDC. Data were insufficient to recommend EMS/VMS. Future studies should prioritize testing of VMS using stronger study designs including control arms and validated, system-independent measures of hand hygiene.

Aging and postural control. A comparison of spontaneous- and induced-sway balance tests.

Two different balance testing methods were compared: (1) measurement of spontaneous postural sway during quiet standing, and (2) measurement of induced postural sway in response to an applied postural perturbation. Eyes-open tests were performed in 64 healthy young and elderly adults and in five elderly subjects with a history of falling. In both balance tests, the sway was defined in terms of the displacement of the center of pressure on the feet. Spontaneous sway was quantified using a number of different amplitude- and frequency-based parameters. Induced sway was measured in response to anterior-posterior acceleration of a platform on which the subject stood. The induced-sway test was specially designed to be safe and nonthreatening for elderly subjects; thus, the platform perturbation was confined to small accelerations and a gentle pseudorandom motion was used. To derive a measure of postural stability, the data from this test were fitted with a model that was then used to predict the response to sudden (transient) perturbations, thereby simulating the response in actual falls. Although both induced- and spontaneous-sway measures demonstrated significant aging-related decreases in stability, the differences were more pronounced for the induced-sway data. Conversely, some of the spontaneous-sway measures were much more successful in distinguishing the fallers from the nonfallers. There was a significant correlation between induced-sway and certain spontaneous-sway measures in the normal young adults; however, in the elderly normals and fallers, the data from the two types of balance tests either showed no correlation or, for certain spontaneous-sway measures, tended to show an inverse relationship.

Urinary dysfunction in a geriatric long-term care population: prevalence and patterns.

More complete data on th prevalence and types of urinary dysfunction in geriatric institutional patients are essential for the management of their urologic problems. Over a 13-month period, a prospective study was conducted of all new admissions to a hospital for long-term care. Eighty percent (277/347) of the newly admitted patients were geriatric (65 or older). Urinary dysfunction was identified in 69.3 percent of the geriatric group; 38.3 percent were incontinent, 20.2 percent bore a urinary diversion device, and 10.8 percent were symptomatic without incontinence. Obtaining reliable information about urologic status posed a significant problem, particularly as 27 percent of the subjects had a mental disorder, including organic brain syndrome or confusion. Thirty percent of all patients questioned were unable to give any history of their own health status. Questioning of both staff and patient to determine reliability of the data revealed that the given information was correct in 77 percent of patients who acknowledged genitourinary dysfunction, and in 83 percent of those who denied it. The study failed to elicit useful data concerning the specificity of symptoms, urologic history, diagnosis and management of urinary dysfunction in this series of geriatric patients under long-term institutional care.

Extent of artificial limb use following rehabilitation.

The extent of prosthesis use is reported for 104 lower limb amputees from the onset of gait training up to 2 years later. Subjects were divided into groups according to age (greater than or equal to 65 years or less than 65 years) and amputation level. An analysis of variance including the factors of age and level of amputation was done. Unilateral trans-tibial (UTT) amputees progressed more quickly during the inpatient gait training program that did unilateral trans-femoral (UTF) subjects (p less than 0.05). UTT subjects also walked more than UTF subjects just prior to discharge (p less than 0.05), during the first year after discharge (p less than 0.01), and during the second year after discharge (p less than 0.01). Similarly, younger patients progressed more quickly in gait training (p less than 0.05) and walked more than older subjects throughout the study period (p less than 0.05). There were no significant interactions between age and amputation. The extent of walking of these amputees is compared with the minimal levels required for them to function in different living environments. At the time of discharge from the inpatient gait training program, older unilateral amputees and trans-femoral amputees were not able to walk the 600 steps a day necessary to manage with a moderate level of support in a one-level apartment or home. The declining number of steps taken in the follow-up period indicated that the UTF subjects might benefit from some special attention paid to their community support needs. These findings are also viewed in the context of limited data available on the extent of walking of non-amputees.

An anatomical comparison of the human and bovine thoracolumbar spine.

The bovine spine has been frequently selected as the model for in vitro mechanical studies. A comparative anatomical study has been presented describing important differences and similarities between selected areas in the adult human and calf thoracolumbar spinal segment. Differences in column length and curvature were observed. The total length of the adult bovine vertebral column was found to be on average 209 cm longer than the adult human spine. Equivalent thoracolumbar lengths were obtained by selecting 6-8 week-old dairy calves, which because of their young age had the benefit of consistent bone density. The bovine spine was found to have only a single cervical lordotic curve and a single thoracolumbar kyphotic curve (2). A quantitative comparison of selected dimensions of vertebrae T6, T12, and L3 was performed, and significant findings are discussed. The bovine spinous processes were found to be on average 111% greater in length at level T6, which contributed to a 56% greater total anterior/posterior length at this level in comparison to the vertebrae of an adult male. A 23% greater bovine intertransverse length at level L3 was also shown. The orientation of the human and bovine superior facets, while being in the same general plane and direction, varied as much as 10.5 and 107% at vertebral level L3 on the two axes measured. These significantly different measurements were considered important factors that can influence experimental results when using the bovine spine as a model.

Production of a reproducible spinal burst fracture for use in biomechanical testing.

We have developed a technique to create a reproducible spinal burst fracture of the 12th vertebral body using 6-8-week-old calf spines with ribs, muscles, and vessels resected. We used the entire thoracolumbar segment of 20 calf spines with a standardized 5-mm-deep slice placed onto the body of T12 and the T11-12 disc. We then delivered a proximal-axial impact to the vertically mounted spine, preflexed to 15 degrees of forward flexion, by dropping a 32-kg weight, guided by a 1.55-m steel rod (potential energy = 487 J). Motion was limited to anterior flexion only, at the T12-13 disc, by splinting the rest of the spinal segments. Fractures were documented with the use of radiographs and computed tomography (CT) scans. We noted disruption of the vertebral column and end plates, fracture of the posterior body wall, fracture of the pedicles, and retropulsion of bony fragments into the neural canal. With the production of a reproducible spinal burst fracture model, various spinal fixation devices can be applied and tested.

Migration, attachment, and orientation of human gingival fibroblasts to root slices, naked and porous-surfaced titanium alloy discs, and Zircalloy 2 discs in vitro.

Cell migration, attachment, and orientation of cultured human gingival fibroblasts (HGF) were measured in relation to four types of specimens: Ti-6Al-4V alloy discs with either ground surfaces or porous structured surfaces, and Zr alloy discs (Zircalloy 2) with either ground surfaces or surfaces modified by being heated to form a thicker oxide cover. Surface-demineralized and non-demineralized root slices were used as controls. Initial cell attachment was measured by means of a 51Cr assay, and cell attachment and orientation following migration by an assay that measures development of the resulting refractile material in relation to the specimen. No significant difference between initial cell attachment to Ti alloy and control demineralized root slices could be detected after one hr using the 51Cr assay. However, with the second assay, cell attachment and orientation at three, seven, 10, and 14 days were significantly higher in relation to surface-demineralized root slices than to all of the metal discs and the non-demineralized root slices. While cell attachment to the surface-ground Ti alloy discs appeared to be higher than that to the porous-surfaced Ti alloy discs at three days and seven days, cell orientation to the porous-surfaced Ti alloy discs and the non-demineralized root slices at days 7, 10, and 14 was greater than that to all of the other metal discs. These data suggest that surface geometry could affect attachment and orientation of cells in vitro.

Biomechanical study of full-contact karate contrasted with boxing.

It is known that boxers suffer a characteristic cumulative brain injury from repeated blows to the head that correlates well with the number of bouts fought. Much less is known about full-contact karate (kickboxing), which is relatively new. In full-contact karate, punches and kicks are actually landed, rather than being focused to culminate just short of an opponent, as practiced in traditional karate. Although a combatant can win on points, the surest means of victory is a knockout. Consequently, fighters strive to land blows to the head. To investigate the relative force of kicks and punches, a dummy head was mounted 175 cm above the floor (to simulate a 50th-percentile man standing erect) and 125 cm above the floor (to simulate the man in a crouched position) on a universal joint permitting motion about three axes. The mechanism was contrived to provide constant rotational stiffness, and springs provided constant restorative moments about the three axes. The texture of soft tissue was simulated by a mask of visco-elastic foamed materials. Fourteen karate experts punched and kicked the dummy. Accelerometer measurements in the 90- to 120-G range indicated that safety-chops (hand protectors) and safety-kicks (foot padding) did not reduce acceleration of the dummy. Ten-ounce boxing gloves mitigated peak acceleration to some extent. Kicks and punches produced accelerations in the same range. Violent acceleration of the head by any means produces injury. The authors conclude that, if full-contact karate is widely practiced, cases of kickboxer's encephalopathy will soon be reported.

Postural sway in amputees and normal subjects.

The postural sway of amputees was investigated quantitatively in fifty patients with above-the-knee amputations and in twenty-nine patients with below-the-knee amputations. The factors evaluated were: (1) the mean speed of sway: (2) the range of movement in the sagittal and coronal planes; and (3) the dependence on vision as indicated by the ratio of eyes-open to eyes-closed values. The results demonstrated that in amputees there is an increased dependence on vision for maintenance of the erect posture. Postural sway in patients with below-the-knee amputations was found to be significantly greater than that in those with above-the-knee amputations. Postural sway increased with age; but the visual dependence for the control of postural sway was independent of age.

In vivo measurement of lumbar spinal creep in two seated postures using magnetic resonance imaging.

STUDY DESIGN: A magnetic resonance imaging technique was developed to measure creep in the lumbar spine in different seated postures. Owing to the fixed size and horizontal orientation constraints of the magnetic resonance imaging system bore, gravitational force was simulated in the horizontal plane while the subject assumed each of two near-seated postures: 1) flexed lumbar, and 2) extended lumbar. OBJECTIVES: One experimental subject was used to determine the feasibility of this technique designed to correlate spinal creep with different seated postures. SUMMARY OF BACKGROUND DATA: Although epidemiologic and pathologic studies have linked the seated posture with low back pain and disc degeneration, few in vivo studies have explored the mechanical response of the lumbar spine to seated postures. METHODS: Creep displacement of four lumbar discs (L3-S1) was measured from unloaded and loaded scans separated by 30 minutes of constant loading. Forty-eight images were measured from three trials in each posture, four sagittal slices per trial. RESULTS: Creep while in an extended posture (3.58 mm) was greater than creep while in a flexed posture (2.92 mm). System resolution was 0.78 mm. CONCLUSION: This technique can be used to discern between creep displacements in different postures.

Functional biomechanics of the spine.

The exact nature of the mechanisms at work during movement of the human spine are not well understood, nor well defined. The spine supports the torso against loads and allows freedom of motion, within physiologic limits, at the same time. A great deal of information characterizing various attributes of the spine is available. Research has provided values for flexural stiffness, axial compliance, range of motion under various loading modalities, and considerably more. This study will focus not on isolated topics, but rather serve as a broad introduction to the behavior of the spine as a whole.

Mechanical response of the lumbar spine to seated postural loads.

STUDY DESIGN: In vitro force and deformation measurements formed the basis for determinate, quasistatic analysis of principal forces in the seated lumbar spine. OBJECTIVES: To explore the relationship between seated postures and the mechanical response in component tissues of lumbar intervertebral joints. SUMMARY OF BACKGROUND DATA: Despite the high prevalence of low back pain syndrome, the precise mechanisms relating specific mechanical loads to spinal degeneration are not well understood. Simultaneous, time-dependent measurement of anterior column forces and articular facet forces has not been presented previously. consequently, a determinate analysis of principal component forces has not been possible. METHODS: Twelve lumbar spines (L1-S1) were subjected to constant loading conditions while in flexed and extended seated postures. Time-dependent forces were measured in the anterior column at the L4 and L5 superior endplates and in the four facets of the L3-L4 and L4-L5 motion segments. A quasi-static analysis of sagittal plane forces was used to compute the remaining principal joint forces, including ligament, disc shear, and facet impingement forces. RESULTS: Component forces changed under static loading in both postures. There were significant differences between the mechanical responses of the two postures. Although the vertical creep displacement was greater in the extended seated posture (3.22 mm versus 2.11 mm), the escalation of forces was more severe in the flexed posture. CONCLUSIONS: The results suggest a mechanism of force balancing in lordotic postures under static loads, whereas flexed postures produce large increases to the tensile forces in the region of the posterior anulus.