A 5-year propensity-matched analysis of perioperative outcomes in patients with chronic kidney disease undergoing bariatric surgery.

BACKGROUND: Bariatric surgery can improve renal function in patients with comorbid chronic kidney disease (CKD) and obesity. Additionally, bariatric surgery can enhance outcomes following renal transplantation. The safety of bariatric surgery in patients with CKD has been debated in the literature. This study evaluates the frequency of perioperative complications associated with CKD. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried from 2015-2019. Patients were included if they had a vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and were stratified based on CKD status. An unmatched and propensity-matched analysis was performed comparing 30-day perioperative outcomes between the groups. RESULTS: A total of 717,809 patients included in this study, 5817(0.8%) had CKD, of whom 2266(0.3%) were on dialysis. 74.3% of patients with CKD underwent VSG with 25.7% underwent RYGB. Comparing RYGB to VSG, patients who underwent RYGB had a higher rate of deep organ space infection (0.7%vs.0.1%,p = 0.021) and re-intervention (5.0% vs. 2.2%,p < 0.001). Within the VSG cohort, a matched analysis was performed for those with CKD and without CKD. The CKD cohort had higher risk of complications such as bleeding (2.1%vs. 0.9%,p < 0.001), readmission (9.3%vs.4.9%,p < 0.001), reoperation (2.7%vs.1.3%,p < 0.001), and need for reintervention (2.2%vs.1.3%,p < 0.001). Notably, patients with CKD also had a higher mortality (0.6%vs.0.2%,p = 0.003). No difference was seen between patients with renal insufficiency and patients on dialysis. CONCLUSION: VSG has been the operation of choice in patients with CKD. Our results showed it is the safer option for patients with CKD compared to RYGB. Although this patient population does have an increased risk of adverse perioperative events, dialysis didn't affect the outcome. Bariatric surgeons who operate on patients with CKD should be well informed and remain vigilant given the increased perioperative risk. The risk is still considerably low, and the potential benefit on renal function and improvement in candidacy for renal transplant outweigh the risk. They should be considered as surgical candidates.

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database.

BACKGROUND: Vertical sleeve gastrectomy (VSG) has demonstrated to be safe; however, controversy remains on how to decrease major complications, particularly bleeding and leaks. There are variations in staple-line reinforcement techniques, including no reinforcement, oversewing, and buttressing. We sought to evaluate the effect of those methods on post-operative complications using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program (MBSAQIP) database. METHODS: The MBSAQIP was queried for patients who underwent VSG during 2015-2019. A propensity-matched analysis was performed between different staple-line reinforcement (SLR) methods, specifically No reinforcement (NR), Oversewing (OS), and Buttressing (BR). The primary outcome of interest was complications within 30 days. RESULTS: A total of 513,354 VSG cases were analyzed. The cohort was majority female (79.0%), with mean (SD) age of 44.2 ± 11.9 years and mean BMI of 45 ± 7.8 kg/m2. Frequency of SLR methods used was 54%BR, 25.6%NR, 10.8% BR + OS, and 9.8%OS. There were no differences in rate of leaks among SLR methods. Compared to NR, BR was associated with decreased rate of reoperations, overall bleeding, and major bleeding (p < 0.05) but prolonged operative time and length of stay (LOS) (p < 0.05). OS was associated with decreased overall bleeding (p < 0.05) but prolonged operative times and length of stay (p < 0.05) compared to NR. Compared to BR, OS was associated with increased operative times, LOS, and rates of post-operative ventilator use, pneumonia, and venous thrombosis (p < 0.05). Patients with bleeding were associated with lower rate of BR (56% vs 61%) and higher rate of NR (34% vs 28%) compared to patients with no bleeding. Bleeding was associated with a greater frequency of leaks (4.4% vs 0.3%), along with higher morbidity and mortality (p < 0.05). CONCLUSIONS: Of the reinforcement methods evaluated, BR and OS were both associated with decreased bleeding despite longer operative times. No method was found to significantly reduce incidence of leaks; however, bleeding was associated with increased incidence of leaks, morbidity, and mortality. The liberal use of SLR techniques is recommended for further optimization of patient outcomes after VSG.

The economic burden experienced by carers of children who had a critical deterioration at a tertiary children's hospital in the United Kingdom (the DETECT study): an online survey.

BACKGROUND: Unplanned critical care admissions following in-hospital deterioration in children are expected to impose a significant burden for carers across a number of dimensions. One dimension relates to the financial and economic impact associated with the admission, from both direct out-of-pocket expenditures, as well as indirect costs, reflecting productivity losses. A robust assessment of these costs is key to understand the wider impact of interventions aiming to reduce in-patient deterioration. This work aims to determine the economic burden imposed on carers caring for hospitalised children that experience critical deterioration events. METHODS: Descriptive study with quantitative approach. Carers responded to an online survey between July 2020 and April 2021. The survey was developed by the research team and piloted before use. The sample comprised 71 carers of children admitted to a critical care unit following in-patient deterioration, at a tertiary children's hospital in the UK. The survey provides a characterisation of the carer's household and estimates of direct non-medical costs grouped in five different expenditure categories. Productivity losses can also be estimated based on the reported information. RESULTS: Most carers reported expenditures associated to the child's admission in the week preceding the survey completion. Two-thirds of working carers had missed at least one workday in the week prior to the survey completion. Moreover, eight in ten carers reported having had to travel from home to the hospital at least once a week. These expenditures, on average, amount to £164 per week, grouped in five categories (38% each to travelling costs and to food and drink costs, with accommodation, childcare, and parking representing 12%, 7% and 5%, respectively). Additionally, weekly productivity losses for working carers are estimated at £195. CONCLUSION: Unplanned critical care admissions for children impose a substantial financial burden for carers. Moreover, productivity losses imply a subsequent cost to society. Even though subsidised hospital parking and on-site accommodation at the hospital contribute to minimising such expenditure, the overall impact for carers remains high. Interventions aiming at reducing emergency critical care admissions, or their length, can be crucial to further contribute to the reduction of this burden. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61279068, date of registration 07/06/2019, retrospectively registered.

Measurement of Self-regulation in Preschool and Elementary Children: A Scoping Review.

AIMS: This scoping review sought to identify and characterize measurement of self-regulation in preschool and elementary aged children. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (ScR) guidelines were applied. Databases from the fields of allied health, education, medicine, and social sciences were searched including: CINAHL, Education Database (ProQuest), Education Research Complete, EMBASE, ERIC, iNFORMIT Combined, Medline, PsychINFO, Social Sciences (ProQuest), Teacher Reference Center, and Web of Science. Articles published between 2015 and 2020 were included. Dual review was utilized at all stages and a third reviewer resolved any conflicts. RESULTS: Sixty-seven studies were included in this review. A range of observational, self-report, teacher report, caregiver report, and observational measures of self-regulation were identified. Included studies were primarily published in education and psychology disciplines, with no studies by occupational therapists identified. CONCLUSIONS: Although a range of measures were identified in this scoping review, the results highlight the lack of consensus regarding self-regulation measurement that occupational therapists use to design and implement therapy programs to address child emotional and behavioral needs.

Tuberous sclerosis complex-associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes.

We aimed to further characterize pancreatic involvement in tuberous sclerosis complex (TSC), with a focus on management of TSC-associated nonfunctional pancreatic neuroendocrine tumors (PNETs). This was a retrospective chart review of a large cohort of TSC patients. A total of 637 patients with a confirmed diagnosis of TSC were seen at the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital. Of the 637 total patients with a confirmed diagnosis of TSC, 28 patients were found to have varying pancreatic findings ranging from simple-appearing cysts to well-differentiated PNETs. Thirteen of the 28 patients had PNET confirmed on pathology; 10 of these tumors were resected at Massachusetts General Hospital. None of the patients had serious perioperative or postoperative complications; only one of the patients had a recurrence following resection. As roughly 4.4% of our TSC patient population had pancreatic involvement, surveillance abdominal imaging should include evaluation of the pancreas instead of limiting to a renal protocol. Additionally, given the low risk of complications and recurrence combined with documented risk of metastasis in TSC-associated PNET, TSC patients with pancreatic lesions suspicious for PNETs should be considered as surgical candidates.

Health professionals' initial experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic paediatric early warning system (the DETECT study): a qualitative interview study.

BACKGROUND: Paediatric early warning systems (PEWS) alert health professionals to signs of a child's deterioration with the intention of triggering an urgent review and escalating care. They can reduce unplanned critical care transfer, cardiac arrest, and death. Electronic systems may be superior to paper-based systems. The objective of the study was to critically explore the initial experiences and perceptions of health professionals about the acceptability of DETECT e-PEWS, and what factors influence its acceptability. METHODS: A descriptive qualitative study (part of The DETECT study) was undertaken February 2020-2021. Single, semi-structured telephone interviews were used. The setting was a tertiary children's hospital, UK. The participants were health professionals working in study setting and using DETECT e-PEWS. Sampling was undertaken using a mix of convenience and snowballing techniques. Participants represented two user-groups: 'documenting vital signs' (D-VS) and 'responding to vital signs' (R-VS). Perceptions of clinical utility and acceptability of DETECT e-PEWS were derived from thematic analysis of transcripts. RESULTS: Fourteen HPs (12 nurses, 2 doctors) participated; seven in D-VS and seven in the R-VS group. Three main themes were identified: complying with DETECT e-PEWS, circumventing DETECT e-PEWS, and disregarding DETECT e-PEWS. Overall clinical utility and acceptability were deemed good for HPs in the D-VS group but there was diversity in perception in the R-VS group (nurses found it more acceptable than doctors). Compliance was better in the D-VS group where use of DETECT e-PEWS was mandated and used more consistently. Some health professionals circumvented DETECT e-PEWS and fell back into old habits. Doctors (R-VS) did not consistently engage with DETECT e-PEWS, which reduced the acceptability of the system, even in those who thought the system brought benefits. CONCLUSIONS: Speed and accuracy of real-time data, automation of triggering alerts and improved situational awareness were key factors that contributed to the acceptability of DETECT e-PEWS. Mandating use of both recording and responding aspects of DETECT e-PEWS is needed to ensure full implementation.

APOBEC3F determinants of HIV-1 Vif sensitivity.

HIV-1 Vif counteracts restrictive APOBEC3 proteins by targeting them for proteasomal degradation. To determine the regions mediating sensitivity to Vif, we compared human APOBEC3F, which is HIV-1 Vif sensitive, with rhesus APOBEC3F, which is HIV-1 Vif resistant. Rhesus-human APOBEC3F chimeras and amino acid substitution mutants were tested for sensitivity to HIV-1 Vif. This approach identified the α3 and α4 helices of human APOBEC3F as important determinants of the interaction with HIV-1 Vif.

Pay-to-Play: The Rising Cost of Subspecialty Conference Attendance for Surgical Residents.

OBJECTIVE: Surgical society conferences play a vital role in academic medicine, offering exposure to subspecialties, networking, and research presentation opportunities for surgical residents. However, the rising costs of attendance pose financial challenges, potentially deterring participation. We aimed to assess changes in conference costs, travel policies, and expenses for general surgery residents in North Carolina (NC) and South Carolina (SC) general surgery residency programs. DESIGN, SETTING, AND PARTICIPANTS: We collected registration data for major surgical society conferences in 2009 and 2019. Airfare estimates were derived from U.S. Department of Transportation data, while hotel costs were calculated based on negotiated rates for conference dates. Miscellaneous expenses were approximated using a per diem rate. Statistical analyses compared costs using paired T-tests (p < 0.05). RESULTS: There was a significant increase in registration costs from 2009 to 2019 (mean: $103 vs. $213; p = 0.04), outpacing inflation. However, there were no statistically significant changes in hotel costs or total attendance expenses over the same period. Flight costs decreased slightly, but not significantly (p = 0.18). CONCLUSION: While this study highlights a notable rise in conference registration fees, total attendance costs remained stable. Nevertheless, the financial burden on residents and programs remains considerable. We recommend surgical societies reassess their registration policies to alleviate costs and enhance access, potentially through increased scholarship opportunities, ensuring conferences remain accessible to all residents.

Parents' experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (the DETECT study): A qualitative interview study.

Background: Failure to recognize and respond to clinical deterioration in a timely and effective manner is an urgent safety concern, driving the need for early identification systems to be embedded in the care of children in hospital. Pediatric early warning systems (PEWS) or PEW scores alert health professionals (HPs) to signs of deterioration, trigger a review and escalate care as needed. PEW scoring allows HPs to record a child's vital signs and other key data including parent concern. Aim: This study aimed to explore the experiences and perceptions of parents about the acceptability of a newly implemented electronic surveillance system (the DETECT surveillance system), and factors that influenced acceptability and their awareness around signs of clinical deterioration and raising concern. Methods: Descriptive, qualitative semi-structured telephone interviews were undertaken with parents of children who had experienced a critical deterioration event (CDE) (n = 19) and parents of those who had not experienced a CDE (non-CDE parents) (n = 17). Data were collected between February 2020 and February 2021. Results: Qualitative data were analyzed using generic thematic analysis. Analysis revealed an overarching theme of trust as a key factor that underpinned all aspects of children's vital signs being recorded and monitored. The main themes reflect three domains of parents' trust: trust in themselves, trust in the HPs, and trust in the technology. Conclusion: Parents' experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (The DETECT system) were positive; they found it acceptable and welcomed the use of new technology to support the care of their child.

Clinical utility and acceptability of a whole-hospital, pro-active electronic paediatric early warning system (the DETECT study): A prospective e-survey of parents and health professionals.

BACKGROUND: Paediatric early warning systems (PEWS) are a means of tracking physiological state and alerting healthcare professionals about signs of deterioration, triggering a clinical review and/or escalation of care of children. A proactive end-to-end deterioration solution (the DETECT surveillance system) with an embedded e-PEWS that included sepsis screening was introduced across a tertiary children's hospital. One component of the implementation programme was a sub-study to determine an understanding of the DETECT e-PEWS in terms of its clinical utility and its acceptability. AIM: This study aimed to examine how parents and health professionals view and engage with the DETECT e-PEWS apps, with a particular focus on its clinical utility and its acceptability. METHOD: A prospective, closed (tick box or sliding scale) and open (text based) question, e-survey of parents (n = 137) and health professionals (n = 151) with experience of DETECT e-PEWS. Data were collected between February 2020 and February 2021. RESULTS: Quantitative data were analysed using descriptive and inferential statistics and qualitative data with generic thematic analysis. Overall, both clinical utility and acceptability (across seven constructs) were high across both stakeholder groups although some challenges to utility (e.g., sensitivity of triggers within specific patient populations) and acceptability (e.g., burden related to having to carry extra technology) were identified. CONCLUSION: Despite the multifaceted nature of the intervention and the complexity of implementation across a hospital, the system demonstrated clinical utility and acceptability across two key groups of stakeholders: parents and health professionals.

A randomized trial of two methods to disclose prognosis to surrogate decision makers in intensive care units.

RATIONALE: Surrogate decision makers and clinicians often have discordant perceptions about a patient's prognosis. There is a paucity of empirical data to guide communication about prognosis. OBJECTIVES: To assess: (1) whether numeric or qualitative statements more reliably convey prognostic estimates; and (2) whether surrogates believe physicians' prognostic estimates. METHODS: A total of 169 surrogate decision makers for intensive care unit patients were randomized to view 1 of 2 versions of a video portraying a simulated family conference involving a hypothetical patient. The videos varied only by whether prognosis was conveyed in numeric terms ("10% chance of surviving") or qualitative terms ("very unlikely" to survive). MEASUREMENTS AND MAIN RESULTS: We assessed: (1) surrogates' personal estimates of the patient's prognosis; and (2) surrogates' understanding of the physician's prognostic estimate. Neither surrogates' personal estimates nor their understanding of the physician's prognostication differed when prognosis was conveyed numerically versus qualitatively (surrogates' estimate, 22 ± 23% chance of survival versus 26 ± 24%, P = 0.26; understanding of physician's estimate, 17 ± 22% chance of survival versus 16 ± 17%, P = 0.62). One in five surrogates estimated the patient's prognosis was greater than 20% more optimistic than the physician's prognostication. Less trust in physicians was associated with larger discrepancies between surrogates' personal estimates and their understanding of the physician's estimate. CONCLUSIONS: Neither numeric nor qualitative statements reliably convey news of a poor prognosis to surrogates in intensive care units. Many surrogates do not view physicians' prognostications as absolutely accurate. Factors other than ineffective communication may contribute to physician-surrogate discordance about prognosis.

A Behavior Sequence Analysis of Victims' Accounts of Stalking Behaviors.

Stalking is a complex issue involving multiple behaviors and interactions between the stalker and their target. Research has typically involved grouping risk behaviors related to stalking; however, the research question in the current research was to what extent a temporal method would allow investigators to map the dynamics of stalking. Behavior Sequence Analysis is a form of systems analysis that examines sequences of events over time, providing statistically significant results from complex real-world data. The Behavior Sequence Analysis method was applied to 39 participants' detailed accounts of stalking written in online forums. The study provides illustration of the antecedents of stalking and how it may initiate and develop through to end of contact. Both stalker behavior and decisions made by victim were included in the models. The results show multiple patterns of stalkers' behaviors; however, the results also clearly show that victims need not perform many behaviors for stalkers to continue with their actions. A main finding was how many behavior transitions occurred before victims felt a significant problem. A large number of participants indicated that they (repeatedly) reported their case of stalking to police and authorities; however, they were mostly dismissed or felt that police did not stop the stalker's actions. A major implication of the current research is providing a novel method to produce a framework that may be used to operationalize definitions of stalking based on coherent frameworks of stalkers' behaviors over time.

"It's not just what the doctor tells me:" factors that influence surrogate decision-makers' perceptions of prognosis.

OBJECTIVE: Physicians and surrogate decision-makers for seriously ill patients often have different views of patients' prognoses. We sought to understand what sources of knowledge surrogates rely on when estimating a patient's prognosis. DESIGN: Prospective, mixed-methods study using face-to-face, semistructured interviews with surrogate decision-makers. SETTING: Four intensive care units at the University of California, San Francisco Medical Center in 2006 to 2007. PARTICIPANTS: Participants were 179 surrogate decision-makers for 142 incapacitated, critically ill patients at high risk for death. MAIN RESULTS: Less than 2% (3 of 179) of surrogates reported that their beliefs about the patients' prognoses hinged exclusively on prognostic information provided to them by physicians. The majority cited other factors in addition to physicians' predictions that also contributed to their beliefs about the patients' prognoses, including perceptions of the patient's individual strength of character and will to live; the patient's unique history of illness and survival; the surrogate's own observations of the patient's physical appearance; the surrogate's belief that their presence at the bedside may improve the prognosis; and the surrogate's optimism, intuition, and faith. For some surrogates, these other sources of knowledge superseded the importance of the physician's prognostication. However, most surrogates endeavored to balance their own knowledge of the patient with physicians' biomedical knowledge. CONCLUSIONS: Surrogates use diverse types of knowledge when estimating their loved ones' prognoses, including individualized attributes of the patient, such as their strength of character and life history, of which physicians may be unaware. Attention to these considerations may help clinicians identify and overcome disagreements about prognosis.

Are physicians' recommendations to limit life support beneficial or burdensome? Bringing empirical data to the debate.

RATIONALE: Although there is a growing belief that physicians should routinely provide a recommendation to surrogates during deliberations about withdrawing life support, there is a paucity of empirical data on surrogates' perspectives on this topic. OBJECTIVES: To understand the attitudes of surrogate decision-makers toward receiving a physician's recommendation during deliberations about whether to limit life support for an incapacitated patient. METHODS: We conducted a prospective, mixed methods study among 169 surrogate decision-makers for critically ill patients. Surrogates sequentially viewed two videos of simulated physician-surrogate discussions about whether to limit life support, which varied only by whether the physician gave a recommendation. MEASUREMENTS AND MAIN RESULTS: The main quantitative outcome was whether surrogates preferred to receive a physicians' recommendation. Surrogates also participated in an in-depth, semistructured interview to explore the reasons for their preference. Fifty-six percent (95/169) of surrogates preferred to receive a recommendation, 42% (70/169) preferred not to receive a recommendation, and 2% (4/169) felt that both approaches were equally acceptable. We identified four main themes that explained surrogates' preferences, including surrogates' perceptions of physicians' appropriate role in life or death decisions and their perceptions of the positive or negative consequences of a recommendation on the physician-surrogate relationship, on the decision-making process, and on long-term regret for the family. CONCLUSIONS: There is no consensus among surrogates about whether physicians should routinely provide a recommendation regarding life support decisions for incapacitated patients. These findings suggest that physicians should ask surrogates whether they wish to receive a recommendation regarding life support decisions and should be flexible in their approach to decision-making.

Surrogate decision-makers' perspectives on discussing prognosis in the face of uncertainty.

RATIONALE: Many physicians are reluctant to discuss a patient's prognosis when there is significant prognostic uncertainty. OBJECTIVES: We sought to understand surrogate decision makers' views regarding whether physicians should discuss prognosis in the face of uncertainty. METHODS: We conducted semi-structured interviews with 179 surrogates for 142 incapacitated patients at high risk of death in four intensive care units at an academic medical center. The interviews explored surrogates' attitudes about whether physicians should discuss prognosis when they cannot be certain their prognostic estimates are correct. We used constant comparative methods to analyze the transcripts. Validation methods included triangulation by multidisciplinary analysis and member checking. MEASUREMENTS AND MAIN RESULTS: Eighty-seven percent (155/179) of surrogates wanted physicians to discuss an uncertain prognosis. We identified five main reasons for this, including surrogates' belief that prognostic uncertainty is unavoidable, that physicians are their only source for prognostic information, and that discussing prognostic uncertainty leaves room for realistic hope, increases surrogates' trust in the physician, and signals a need to prepare for possible bereavement. Twelve percent (22/179) of surrogates felt that discussions about an uncertain prognosis should be avoided. The main explanation was that it is not worth the potential emotional distress if the prognostications are incorrect. Surrogates suggested that physicians should explicitly discuss uncertainty when prognosticating. CONCLUSIONS: The majority of surrogates of patients that are critically ill want physicians to disclose their prognostic estimates even if they cannot be certain they are correct. This stems from surrogates' belief that prognostic uncertainty is simultaneously unavoidable and acceptable.

Hope, truth, and preparing for death: perspectives of surrogate decision makers.

BACKGROUND: Although many physicians worry that openly discussing a poor prognosis will cause patients and families to lose hope, surrogate decision makers' perspectives on this topic are largely unknown. OBJECTIVE: To determine surrogate decision makers' attitudes toward balancing hope and telling the truth when discussing prognosis. DESIGN: Prospective, mixed-methods cohort study. SETTING: 4 intensive care units at the University of California, San Francisco, Medical Center, San Francisco, California. PARTICIPANTS: 179 surrogate decision makers for incapacitated patients at high risk for death. MEASUREMENTS: One-on-one, semistructured interviews with surrogates were conducted on the patients' 5th day of receiving mechanical ventilation. Constant comparative methods were used to inductively develop a framework to describe participants' responses. Validation methods included multidisciplinary analysis and member checking. RESULTS: Overall, 93% (166 of 179) of surrogates felt that avoiding discussions about prognosis is an unacceptable way to maintain hope. The main explanatory theme was that timely discussion of prognosis is essential to allow family members to prepare emotionally and logistically for the possibility of a patient's death. Other themes that emerged included surrogates' belief that an accurate understanding of a patient's prognosis allows them to better support the patient and each other, a moral aversion to the idea of false hope, the perception that physicians have an obligation to discuss prognosis, and the notion that some surrogates look to physicians primarily for truth and seek hope elsewhere. A few surrogates (6 of 179) felt that physicians should withhold prognostic information because of a belief that discussing death could be emotionally damaging to the family or could negatively affect the patient's health. LIMITATION: The authors did not longitudinally assess whether early disclosure about prognosis predicts fewer adverse bereavement outcomes. CONCLUSION: Most surrogates of critically ill patients do not view withholding prognostic information as an acceptable way to maintain hope, largely because timely discussions about prognosis help families begin to prepare emotionally, existentially, and practically for the possibility that a patient will die.

Comparison of elderly and young patient populations treated with deep brain stimulation for Parkinson's disease: long-term outcomes with up to 7 years of follow-up.

OBJECTIVE: Deep brain stimulation (DBS) is the procedure of choice for Parkinson's disease (PD). It has been used in PD patients younger than 70 years because of better perceived intra- and postoperative outcomes than in patients 70 years or older. However, previous studies with limited follow-up have demonstrated benefits associated with the treatment of elderly patients. This study aims to evaluate the long-term outcomes in elderly PD patients treated with DBS in comparison with a younger population. METHODS: PD patients treated with DBS at the authors' institution from 2008 to 2014 were divided into 2 groups: 1) elderly patients, defined as having an age at surgery ≥ 70 years, and 2) young patients, defined as those < 70 years at surgery. Functional and medical treatment outcomes were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), levodopa-equivalent daily dose (LEDD), number of daily doses, and number of anti-PD medications. Study outcomes were compared using univariate analyses, 1-sample paired t-tests, and 2-sample t-tests. RESULTS: A total of 151 patients were studied, of whom 24.5% were ≥ 70 years. The most common preoperative Hoehn and Yahr stages for both groups were 2 and 3. On average, elderly patients had more comorbidities at the time of surgery than their younger counterparts (1 vs 0, p = 0.0001) as well as a higher average LEDD (891 mg vs 665 mg, p = 0.008). Both groups experienced significant decreases in LEDD following surgery (elderly 331.38 mg, p = 0.0001; and young 108.6 mg, p = 0.0439), with a more significant decrease seen in elderly patients (young 108.6 mg vs elderly 331.38 mg, p = 0.0153). Elderly patients also experienced more significant reductions in daily doses (young 0.65 vs elderly 3.567, p = 0.0344). Both groups experienced significant improvements in motor function determined by reductions in UPDRS III scores (elderly 16.29 vs young 12.85, p < 0.0001); however, reductions in motor score between groups were not significant. Improvement in motor function was present for a mean follow-up of 3.383 years postsurgery for the young group and 3.51 years for the elderly group. The average follow-up was 40.6 months in the young group and 42.2 months in the elderly group. CONCLUSIONS: This study found long-term improvements in motor function and medication requirements in both elderly and young PD patients treated with DBS. These outcomes suggest that DBS can be successfully used in PD patients ≥ 70 years. Further studies will expand on these findings.

Genetic and pharmacological manipulations that alter metabolism suppress seizure-like activity in Drosophila.

There is increasing evidence that alterations in metabolism can affect seizure susceptibility in a wide range of organisms. In order to investigate the link between metabolism and seizures, we took advantage of a group of Drosophila mutants, the Bang-sensitive (BS) paralytics, which are 3-10 times more susceptible to seizure-like activity (SLA) than wild type flies following a variety of stimuli including mechanical shock. To alter metabolism, we introduced the atsugari (atu) mutation into three of the BS mutants, easily shocked (eas), bang senseless (bss), and technical knockout (tko). The atu mutants, which exhibit reduced expression of the Drosophila ortholog of dystroglycan gene, have previously been shown to have a higher metabolic rate than wild type flies. Following mechanical shock, all three BS;atu double mutants displayed a reduction in SLA and the eas;atu and tko;atu double mutants recovered from the shock quicker than the respective single mutant BS flies. In addition, the eas;atu and tko;atu flies displayed higher levels of metabolism as compared to the single mutant BS flies. To further study the correlation between metabolism and seizure susceptibility, the three BS strains were fed a sulfonylurea drug (tolbutamide) known to both increase heamolymph glucose concentrations and stimulate lipid metabolism in flies. Following mechanical shock, the eas and tko mutants fed tolbutamide displayed less SLA and recovered quicker than unfed flies. While the bss mutants fed tolbutamide did not display a reduction in SLA, they did recover quicker than unfed controls. These data indicate that the upregulation of metabolism can have a protective effect against seizure susceptibility, a result that suggests new avenues for possible drug development.

Identification of the lateral position of a virtual object based on echoes by humans.

Echolocation offers a promising approach to improve the quality of life of people with blindness although little is known about the factors influencing object localisation using a 'searching' strategy. In this paper, we describe a series of experiments using sighted and blind human listeners and a 'virtual auditory space' technique to investigate the effects of the distance and orientation of a reflective object and the effect of stimulus bandwidth on ability to identify the right-versus-left position of the object, with bands of noise and durations from 10-400 ms. We found that performance reduced with increasing object distance. This was more rapid for object orientations where mirror-like reflection paths do not exist to both ears (i.e., most possible orientations); performance with these orientations was indistinguishable from chance at 1.8 m for even the best performing listeners in other conditions. Above-chance performance extended to larger distances when the echo was artificially presented in isolation, as might be achieved in practice by an assistive device. We also found that performance was primarily based on information above 2 kHz. Further research should extend these investigations to include other factors that are relevant to real-life echolocation.

Crystal structure of the DNA cytosine deaminase APOBEC3F: the catalytically active and HIV-1 Vif-binding domain.

Human APOBEC3F is an antiretroviral single-strand DNA cytosine deaminase, susceptible to degradation by the HIV-1 protein Vif. In this study the crystal structure of the HIV Vif binding, catalytically active, C-terminal domain of APOBEC3F (A3F-CTD) was determined. The A3F-CTD shares structural motifs with portions of APOBEC3G-CTD, APOBEC3C, and APOBEC2. Residues identified to be critical for Vif-dependent degradation of APOBEC3F all fit within a predominantly negatively charged contiguous region on the surface of A3F-CTD. Specific sequence motifs, previously shown to play a role in Vif susceptibility and virion encapsidation, are conserved across APOBEC3s and between APOBEC3s and HIV-1 Vif. In this structure these motifs pack against each other at intermolecular interfaces, providing potential insights both into APOBEC3 oligomerization and Vif interactions.