Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib.

Aim: To investigate real-world time to next treatment in patients with chronic lymphocytic leukemia initiating first-line (1L) ibrutinib or acalabrutinib. Materials & methods: US specialty pharmacy electronic medical records (21/11/2018-30/4/2022) were used; patients initiated 1L on/after 21/11/2019 (acalabrutinib approval). Results: Among 710 patients receiving ibrutinib, 5.9% initiated next treatment (mean time to initiation = 9.2 months); among 373 patients receiving acalabrutinib, 7.5% initiated next treatment (mean time to initiation = 5.9 months). Adjusting for baseline characteristics, acalabrutinib-treated patients were 89% more likely to initiate next treatment (hazard ratio = 1.89; p = 0.016). Conclusion: This study addresses a need for real-world comparative effectiveness between 1L ibrutinib and acalabrutinib and shows that next treatment (a clinically meaningful measure for real-world progression) occurred less frequently with 1L ibrutinib.

Ibrutinib and acalabrutinib are oral medications taken once-daily and twice-daily, respectively. They are recommended as initial treatment for chronic lymphocytic leukemia (CLL). The goal of this study was to compare the efficacy of these treatments as initial treatment for CLL. To meet this goal, real-world US specialty pharmacy electronic medical records between 11/21/2018­4/30/2022 were used. Patients treated with ibrutinib or acalabrutinib as initial treatment for CLL were studied. Treatment had to be started on or after the date of acalabrutinib approval for CLL (11/21/2019). Time to next treatment was used to estimate real-world disease progression. It was defined as the time from the initiation of initial treatment with ibrutinib or acalabrutinib to the initiation of a next treatment. Study results showed that patients were observed for a median of up to 1.5 years. Over this period, next treatment was more likely for acalabrutinib (7.5%) compared with ibrutinib (5.9%). After adjusting for differences in patient characteristics, next treatment was 89% more likely with acalabrutinib than ibrutinib. This study addresses a need to compare the effectiveness of initial treatment with ibrutinib and acalabrutinib in the real-world. It helps better contextualize results from clinical trial data and shows that next treatment occurred less frequently with ibrutinib.

New horizons in the diagnosis and management of Alzheimer's Disease in older adults.

Alzheimer's Disease (ad) is the most common cause of dementia, and in addition to cognitive decline, it directly contributes to physical frailty, falls, incontinence, institutionalisation and polypharmacy in older adults. Increasing availability of clinically validated biomarkers including cerebrospinal fluid and positron emission tomography to assess both amyloid and tau pathology has led to a reconceptualisation of ad as a clinical-biological diagnosis, rather than one based purely on clinical phenotype. However, co-pathology is frequent in older adults which influence the accuracy of biomarker interpretation. Importantly, some older adults with positive amyloid or tau pathological biomarkers may never experience cognitive impairment or dementia. These strides towards achieving an accurate clinical-biological diagnosis are occurring alongside recent positive phase 3 trial results reporting statistically significant effects of anti-amyloid Disease-Modifying Therapies (DMTs) on disease severity in early ad. However, the real-world clinical benefit of these DMTs is not clear and concerns remain regarding how trial results will translate to real-world clinical populations, potential adverse effects (including amyloid-related imaging abnormalities), which can be severe and healthcare systems readiness to afford and deliver potential DMTs to appropriate populations. Here, we review recent advances in both clinical-biological diagnostic classification and future treatment in older adults living with ad. Advocating for access to both more accurate clinical-biological diagnosis and potential DMTs must be done so in a holistic and gerontologically attuned fashion, with geriatricians advocating for enhanced multi-component and multi-disciplinary care for all older adults with ad. This includes those across the ad severity spectrum including older adults potentially ineligible for emerging DMTs.

Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

The quality of pharmacist-led community warfarin management across 2 provinces in Canada: A cross-sectional observational study.

Background: Guidelines for anticoagulation management services recommend personnel be specially trained in warfarin management and suggest using tools such as decision-support software. To date, there have been no Canadian studies documenting the quality of warfarin management using a similar guideline recommended approach. Methods: A cross-sectional, retrospective observational study was conducted to measure the quality of pharmacist-led warfarin management using point-of-care international normalized ratio (INR) testing and decision-support software in various ambulatory settings in Canada. Settings included 4 family health teams in Ontario and 40 community pharmacies across Nova Scotia. Quality was measured using time in therapeutic range (TTR) and was reported in 3 manners: mean TTR, median TTR and time-weighted mean TTR. Results: The primary outcome included 963 patients. The combined mean and median TTR for the 2019 Ontario family health teams and Nova Scotia pharmacies was 74.2% and 77.3% (interquartile range 64%-87.9%), respectively. The time-weighted mean TTR was 76.3%. Discussion: To the best of our knowledge, the TTR achieved by this model of care is the highest reported in Canadian general practice. Since Thrombosis Canada defines good-quality warfarin management as a TTR of 60% or greater, and many studies have reported an association between higher TTR values and lower rates of thrombosis and hemorrhage, this model of care may have significant benefits for patients. Conclusion: This study demonstrates the high quality of anticoagulation management provided by specially trained pharmacists using point-of-care INR testing and decision-support software. These results support expanded access to this service for all Canadians. Can Pharm J (Ott) 2024;157:xx-xx.

What Are the Challenges Related to Family Planning, Pregnancy, and Parenthood Faced by Women in Orthopaedic Surgery? A Systematic Review.

BACKGROUND: Orthopaedic surgery is the surgical specialty with the lowest proportion of women. Conflicting evidence regarding the potential challenges of pregnancy and parenthood in orthopaedics, such as the implications of delayed childbearing, may be a barrier to recruitment and retainment of women in orthopaedic surgery. A summary of studies is needed to ensure that women who have or wish to have children during their career in orthopaedic surgery are equipped with the relevant information to make informed decisions. QUESTIONS/PURPOSES: In this systematic review, we asked: What are the key gender-related barriers pertaining to (1) family planning, (2) pregnancy, and (3) parenthood that women in orthopaedic surgery face? METHODS: Embase, MEDLINE, and PsychINFO were searched on June 7, 2021, for studies related to pregnancy or parenthood as a woman in orthopaedic surgery. Inclusion criteria were studies in the English language and studies describing the perceptions or experiences of attending surgeons, trainees, or program directors. Studies that sampled surgical populations without specific reference to orthopaedics were excluded. Quantitative and qualitative analyses were performed to identify important themes. Seventeen articles including surveys (13 studies), selective reviews (three studies), and an environmental scan (one study) met the inclusion criteria. The population sampled included 1691 attending surgeons, 864 trainees, and 391 program directors in the United States and United Kingdom. The Risk of Bias Instrument for Cross-Sectional Surveys of Attitudes and Practices tool was used to evaluate the risk of bias in survey studies. A total of 2502 women and 560 men were sampled in 13 surveys addressing various topics related to pregnancy, parenthood, and family planning during an orthopaedic career. Three selective reviews provided information on occupational hazards in the orthopaedic work environment during pregnancy, while one environmental scan outlined the accessibility of parental leave policies at 160 residency programs. Many of the survey studies did not report formal clarity, validity, or reliability assessments, therefore increasing their risk of bias. However, our analysis of the provided instruments as well as the consistency of identified themes across multiple survey studies suggests the evidence we aggregated was sufficiently robust to answer the research questions posed in the current systematic review. RESULTS: These data revealed that many women have witnessed or experienced discrimination related to pregnancy and parenthood, at times resulting in a decision to delay family planning. In one study, childbearing was reportedly delayed by 67% of respondents (304 of 452) because of their career choice in orthopaedics. Orthopaedic surgeons were more likely to experience pregnancy complications (range 24% to 31%) than the national mean in the United States (range 13% to 17%). Lastly, despite these challenging conditions, there was often limited support for women who had or wished to start a family during their orthopaedic surgery career. Maternity and parental leave policies varied across training institutions, and only 55% (56 of 102) of training programs in the United States offered parental leave beyond standard vacation time. CONCLUSION: The potential negative effects of these challenges on the orthopaedic gender gap can be mitigated by increasing the availability and accessibility of information related to family planning, parental leave, and return to clinical duties while working as a woman in orthopaedic surgery. Future research could seek to provide a more global perspective and specifically explore regional variation in the environment faced by pregnancy or parenting women in orthopaedic surgery. LEVEL OF EVIDENCE: Level III, prognostic study.

Cost Evaluation of Minimally Invasive Tissue Sampling (MITS) Implementation in Low- and Middle-Income Countries.

BACKGROUND: Low- and middle-income countries (LMICs) face disproportionately high mortality rates, yet the causes of death in LMICs are not robustly understood, limiting the effectiveness of interventions to reduce mortality. Minimally invasive tissue sampling (MITS) is a standardized postmortem examination method that holds promise for use in LMICs, where other approaches for determining cause of death are too costly or unacceptable. This study documents the costs associated with implementing the MITS procedure in LMICs from the healthcare provider perspective and aims to inform resource allocation decisions by public health decisionmakers. METHODS: We surveyed 4 sites in LMICs across Sub-Saharan Africa and South Asia with experience conducting MITS. Using a bottom-up costing approach, we collected direct costs of resources (labor and materials) to conduct MITS and the pre-implementation costs required to initiate MITS. RESULTS: Initial investments range widely yet represent a substantial cost to implement MITS and are determined by the existing infrastructure and needs of a site. The costs to conduct a single case range between $609 and $1028 per case and are driven by labor, sample testing, and MITS supplies costs. CONCLUSIONS: Variation in each site's use of staff roles and testing protocols suggests sites conducting MITS may adapt use of resources based on available expertise, equipment, and surveillance objectives. This study is a first step toward necessary examinations of cost-effectiveness, which may provide insight into cost optimization and economic justification for the expansion of MITS.

Sequencing of PD-1/L1 Inhibitors and Carboplatin Based Chemotherapy for Cisplatin Ineligible Metastatic Urothelial Carcinoma.

PURPOSE: Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval1L-2L) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival. RESULTS: In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.

Education needed to improve antimicrobial use during end-of-life care of older adults with advanced cancer: A cross-sectional survey.

BACKGROUND: Antimicrobial use during end-of-life care of older adults with advanced cancer is prevalent. Factors influencing the decision to prescribe antimicrobials during end-of-life care are not well defined. AIM: To evaluate factors influencing medicine subspecialists to prescribe intravenous and oral antimicrobials during end-of-life care of older adults with advanced cancer to guide an educational intervention. DESIGN: 18-item single-center cross-sectional survey. SETTING/PARTICIPANTS: Inpatient medicine subspecialists in 2018. RESULTS: Of 186 subspecialists surveyed, 67 (36%) responded. Most considered withholding antimicrobials at the time of clinical deterioration during hospitalization (n = 54/67, 81%), viewed the initiation of additional intravenous antimicrobials as escalation of care (n = 44/67, 66%), and believed decision-making should involve patients or surrogates and providers (n = 64/67, 96%). Fifty-one percent (n = 30/59) of respondents who conducted advance care planning did not discuss antimicrobials. Barriers to discussing end-of-life antimicrobials included the potential to overwhelm patients or families, challenges of withdrawing antimicrobials, and insufficient training. CONCLUSIONS: Although the initiation of additional intravenous antimicrobials was viewed as escalation of care, antimicrobials were not routinely discussed during advance care planning. Educational interventions that promote recognition of antimicrobial-associated adverse events, incorporate antimicrobial use into advance care plans, and offer communication simulation training around the role of antimicrobials during end-of-life care are warranted.

Multimodal Measurements of Brain Tissue Metabolism and Perfusion in a Neonatal Model of Hypoxic-Ischaemic Injury.

This is the first multimodal study of cerebral tissue metabolism and perfusion post-hypoxic-ischaemic (HI) brain injury using broadband near-infrared spectroscopy (bNIRS), diffuse correlation spectroscopy (DCS), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). In seven piglet preclinical models of neonatal HI, we measured cerebral tissue saturation (StO2), cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), changes in the mitochondrial oxidation state of cytochrome c oxidase (oxCCO), cerebral glucose metabolism (CMRglc) and tissue biochemistry (Lac+Thr/tNAA). At baseline, the parameters measured in the piglets that experience HI (not controls) were 64 ± 6% StO2, 35 ± 11 ml/100 g/min CBF and 2.0 ± 0.4 µmol/100 g/min CMRO2. After HI, the parameters measured were 68 ± 6% StO2, 35 ± 6 ml/100 g/min CBF, 1.3 ± 0.1 µmol/100 g/min CMRO2, 0.4 ± 0.2 Lac+Thr/tNAA and 9.5 ± 2.0 CMRglc. This study demonstrates the capacity of a multimodal set-up to interrogate the pathophysiology of HIE using a combination of optical methods, MRS, and PET.

Assessing Advanced Communication Skills via Objective Structured Clinical Examination: A Comparison of Faculty Versus Self, Peer, and Standardized Patient Assessors.

Construct: The construct addressed in this study is assessment of advanced communication skills among senior medical students. Background: The question of who should assess participants during objective structured clinical examinations (OSCEs) has been debated, and options discussed in the literature have included peer, self, standardized patient, and faculty assessment models. What is not known is whether same-level peer assisted learning can be utilized for formative assessment of advanced communication skills when no faculty, standardized patients, or other trained assessors are involved in providing feedback. If successful, such an educational model would optimize resource utilization and broaden the scope of topics that could be covered in formative OSCEs. Approach: The investigators developed a 4-station formative OSCE focused on advanced communication skills for senior medical students, and evaluated the concordance of assessment done by same-level peers, self, standardized patients, and faculty for 45 students. After each station, examinees completed a self-assessment checklist and received checklist-based assessment and verbal feedback from same-level peers only. Standardized patients completed checklist-based assessments outside the room, and faculty did so after the OSCE via video review; neither group provided direct feedback to examinees. The investigators assessed inter-rater agreement and mean difference scores on the checklists using faculty score as the gold standard. Findings: There was fair to good overall agreement among self, same-level peer, standardized patient, and faculty-assessment of advanced communication skills. Relative to faculty, peer and standardized patient assessors overestimated advanced communication skills, while self-assessments underestimated skills. Conclusions: Self and same-level peer-assessment may be a viable alternative to faculty assessment for a formative OSCE on advanced communication skills for senior medical students.

Distress Management, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma.

BACKGROUND: The outcome of patients who progress on front-line immune-based combination regimens (IC) including immune checkpoint inhibitors (CPI) and receive subsequent systemic therapy is unknown. METHODS: Retrospective analysis of consecutive patients with clear-cell mRCC who progressed on one of seven clinical trials investigating an IC and received ≥1 line of subsequent VEGFR TKI therapy. RESULTS: Thirty-three patients [median age 57 (37-77), 85% male, 73% ECOG 0] were included. For evaluable patients (N = 28), the best response to first subsequent therapy was 29% partial response, 54% stable disease, and 18% progressive disease. The median PFS (mPFS) for first subsequent therapy was 6.4 months (95% CI, 4.4-8.4); no difference in mPFS by prior type of IC (VEGFR TKI-CPI vs. CPI-CPI) was noted (p = 0.310). Significant AEs were observed in 30% of patients, more frequently transaminitis (9%). CONCLUSIONS: VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy.

Effectiveness of a multifaceted intervention to reduce night-time sedative use in a rehabilitation unit: a pre-post intervention study.

Background: night-time sedation prescribed during a hospital stay can result in long-term use of such medications in older people. We examined the effectiveness of a multifaceted intervention to reduce night time sedation in an inpatient rehabilitation unit. Methods: an initial retrospective survey of night-time sedative use was followed by prospective re-evaluation after a number of changes were made including education of staff and of patients regarding the potential hazards of sedative medications, measures to promote sleep hygiene and facilitate a 'quiet time' after 10 pm and development of a withdrawal protocol for patients on long-term night sedation. The primary outcome measures were the proportions of patients started on night sedation in the unit and the proportion of those using night sedation where a dose reduction was attempted before and after the intervention. Results: night sedation was prescribed for 22/68 (32.4%) subjects in the pre- and 23/169 (13.6%) subjects in the post-intervention surveys (P = 0.001); medication started while in the unit dropped from 10 (14.7%) to 1 (0.6%) (P < 0.0001). There was an improvement in the proportion of patients using night sedation where an attempt was made to reduce the dosage of or eliminate sedative drug use prior to discharge after the intervention was introduced (3/22 (13.6%) vs 14/23 (60.9%) (P = 0.001)). Conclusions: a multifaceted intervention, including ongoing education, audit and feedback and changes to unit practices to promote a 'quiet time' at night, leads to a substantial reduction in the use of night sedation in inpatients.

Broadband NIRS Cerebral Cytochrome-C-Oxidase Response to Anoxia Before and After Hypoxic-Ischaemic Injury in Piglets.

Perinatal hypoxic ischaemic (HI) encephalopathy is associated with severe neurodevelopment problems and mortality. This study uses broadband continuous-wave near-infrared spectroscopy (NIRS) to assess the early changes in cerebral oxygenation and metabolism after HI injury in an animal model using controlled anoxia events. Anoxia was induced before and 1 h after various levels of HI injury to assess the metabolic response via the changes in the oxidation state of cytochrome-c-oxidase (oxCCO), a marker of oxidative metabolism. The oxCCO responses to anoxia were classified into five categories: increase, no change, decrease, biphasic and triphasic responses. The most common response (54%) was a biphasic decrease in oxCCO. A change in the classification of the metabolic response to anoxia after HI injury indicated a severe injury, as determined by proton magnetic resonance spectroscopy, with 86% sensitivity. This shows that broadband NIRS can identify disturbances to cerebral metabolism in the first hours after severe HI injury.

Device-assisted tensioning is associated with lower rates of graft failure when compared to manual tensioning in ACL reconstruction.

PURPOSE: To describe (1) the current graft tensioning practices in ACL reconstruction (ACLR) and, (2) the failure rates with the use of manual tensioning, or device-assisted tensioning at the time of graft fixation. METHODS: The electronic databases MEDLINE, EMBASE, and PubMed were searched independently by two reviewers from database inception to search date on January 21, 2017. Inclusion criteria were studies reporting graft tensioning method and rate of graft failure. The definition of graft failure used was: (1) side-to-side instrumented laxity > 5 mm, (2) Lachman 2 +, (3) positive pivot-shift testing, (4) MRI-confirmed graft rupture or, (5) need for revision surgery. RESULTS: A total of 3379 patients and 3380 knees were treated with ACL reconstruction and followed for an average of 41.7 months (range 4-145 months). ACLR with manual tensioning was performed on 1518 (51.9%) patients and device-assisted tensioning was performed on 1802 (48.1%) patients. The average knee position reported was 29.2° in single-bundle ACLR and 22.9° in double-bundle ACLR. The median amount of tension used in manual tensioning was 'maximum manual tension' and 50 N in device-assisted tensioning. Overall, the failure rate in studies reporting manual tensioning was 8.9% compared to 4.3% in device-assisted tensioning. CONCLUSION: Both manual tensioning and device-assisted tensioning are associated with low overall failure rates (< 10%) in ACLR; however, there is a higher rate of reported failure with manual tensioning compared to device-assisted tensioning. These findings highlight the need to investigate variations in graft tensioning practice, such as specific tension devices and their parameters, with high-quality, randomized controlled trials to elucidate details of their clinical impact. LEVEL OF EVIDENCE: Level IV, systematic review of level I-IV studies.

Surgical Management of Deep Gluteal Syndrome Causing Sciatic Nerve Entrapment: A Systematic Review.

PURPOSE: To assess the causes, surgical indications, patient-reported clinical outcomes, and complications in patients with deep gluteal syndrome causing sciatic nerve entrapment. METHODS: Three databases (PubMed, Ovid [MEDLINE], and Embase) were searched by 2 reviewers independently from database inception until September 7, 2016. The inclusion criteria were studies reporting on both arthroscopic and open surgery and those with Level I to IV evidence. Systematic reviews, conference abstracts, book chapters, and technical reports with no outcome data were excluded. The methodologic quality of the studies was assessed with the MINORS (Methodological Index for Non-randomized Studies) tool. RESULTS: The search identified 1,539 studies, of which 28 (481 patients; mean age, 48 years) were included for assessment. Of the studies, 24 were graded as Level IV, 3 as Level III, and 1 as Level II. The most commonly identified causes were iatrogenic (30%), piriformis syndrome (26%), trauma (15%), and non-piriformis (hamstring, obturator internus) muscle pathology (14%). The decision to pursue surgical management was made based on clinical findings and diagnostic investigations alone in 50% of studies, whereas surgical release was attempted only after failed conservative management in the other 50%. Outcomes were positive, with an improvement in pain at final follow-up (mean, 23 months) reported in all 28 studies. The incidence of complications from these procedures was low: Fewer than 1% and 8% of open surgical procedures and 0% and fewer than 1% of endoscopic procedures resulted in major (deep wound infection) and minor complications, respectively. CONCLUSIONS: Although most of the studies identified were case series and reports, the results consistently showed improvement in pain and a low incidence of complications, particularly for endoscopic procedures. These findings lend credence to surgical management as a viable option for buttock pain caused by deep gluteal syndrome and warrant further investigation. LEVEL OF EVIDENCE: Level IV, systematic review of Level II through IV studies.

Efficacy of Selective Brain Cooling Using a Nasopharyngeal Method in Piglets.

BACKGROUND: Mild hypothermia is an effective neuroprotective strategy for a variety of acute brain injuries. Cooling the nasopharynx may offer the capability to cool the brain selectively due to anatomic proximity of the internal carotid artery to the cavernous sinus. This study investigated the feasibility and efficiency of nasopharyngeal brain cooling by continuously blowing room temperature or cold air at different flow rates into the nostrils of normal newborn piglets. METHODS: Experiments were conducted on thirty piglets (n = 30, weight = 2.7 ± 1.5 kg). Piglets were anesthetized with 1­2% isoflurane and were randomized to receive one of four different nasopharyngeal cooling treatments: I. Room temperature at a flow rate of 3­4 L min(−1) (n = 6); II. −1 ± 2 °C at a flow rate of 3­4 L min(−1) (n = 6); III. Room temperature at a flow rate of 14­15 L min(−1) (n = 6); IV. −8 ± 2 °C at a flow rate of 14­15 L min(−1) (n = 6). To control for the normal thermal regulatory response of piglets without nasopharyngeal cooling, a control group of piglets (n = 6) had their brain temperature monitored without nasopharyngeal cooling. The duration of treatment was 60 min, with additional 30 min of observation. RESULTS: In group I, median cooling rate was 1.7 ± 0.9 °C/h by setting the flow rate of room temperature air to 3­4 L min(−1). Results of comparing different temperatures and flow rates in the nasopharyngeal cooling approach reveal that the brain temperature could be reduced rapidly at a rate of 5.5 ± 1.1 °C/h by blowing −8 ± 2 °C air at a flow rate of 14­15 L min(−1). CONCLUSIONS: Nasopharyngeal cooling via cooled insufflated air can lower the brain temperature, with higher flows and lower temperatures of insufflated air being more effective.

Functional trajectories in the year before hospice.

PURPOSE: We undertook a study to identify distinct functional trajectories in the year before hospice, to determine how patients with these trajectories differ according to demographic characteristics and hospice diagnosis, and to evaluate the association between these trajectories and subsequent outcomes. METHODS: From an ongoing cohort study of 754 community-living persons aged 70 years or older, we evaluated data on 213 persons who were subsequently enrolled in hospice from March 1998 to December 2011. Disability in 13 basic, instrumental, and mobility activities was assessed during monthly telephone interviews through June 2012. RESULTS: In the year before hospice, we identified 5 clinically distinct functional trajectories, representing worsening cumulative burden of disability: late decline (10.8%), accelerated (10.8%), moderate (21.1%), progressively severe (24.9%), and persistently severe (32.4%). Participants with a cancer diagnosis (34.7%) had the most favorable functional trajectories (ie, lowest burden of disability), whereas those with neurodegenerative disease (21.1%) had the worst. Median survival in hospice was only 14 days and did not differ significantly by functional trajectory. Compared with participants in the persistently severe trajectory, those in the moderate trajectory had the highest likelihood of surviving and being independent in at least 1 activity in the month after hospice admission (adjusted odds ratio = 5.5; 95% CI, 1.9-35.9). CONCLUSIONS: The course of disability in the year before hospice differs greatly among older persons but is particularly poor among those with neurodegenerative disease. Late admission to hospice (as shown by the short survival), coupled with high levels of severe disability before hospice, highlight potential unmet palliative care needs for many older persons at the end of life.

Pre-entry student clinical placement demand: can it be met?

OBJECTIVES: The Clinical Education Workload Management Initiative (the Initiative) is a unique, multiprofessional, jurisdiction-wide approach and reform process enshrined within an industrial agreement. The Initiative enabled significant investment in allied health clinical education across Queensland public health services to address the workload associated with providing pre-entry clinical placements. This paper describes the outcomes of a quality review activity to measure the impact of the Initiative on placement capacity and workload management for five allied health professions. Data related to several key factors impacting on placement supply and demand in addition to qualitative perspectives from workforce surveys are reported. METHODS: Data from a range of quality review actions including collated placement activity data, and workforce and student cohort statistics were appraised. Stakeholder perspectives reported in surveys were analysed for emerging themes. RESULTS: Placement offers showed an upward trend in the context of increased university program and student numbers and in contrast with a downward trend in full-time equivalent (FTE) staffnumbers. Initiative-funded positions were identified as a major factor in individual practitioners taking more students, and staff and managers valued the Initiative-funded positions' support before and during placements, in the coordination of placements, and in building partnerships with universities. CONCLUSIONS: The Initiative enabled a co-ordinated response to meeting placement demand and enhanced collaborations between the health and education sectors. Sustaining pre-entry student placement provision remains a challenge for the future.

Quantifying cerebral blood flow in an adult pig ischemia model by a depth-resolved dynamic contrast-enhanced optical method.

Dynamic contrast-enhanced (DCE) near-infrared (NIR) methods have been proposed for bedside monitoring of cerebral blood flow (CBF). These methods have primarily focused on qualitative approaches since scalp contamination hinders quantification. In this study, we demonstrate that accurate CBF measurements can be obtained by analyzing multi-distance time-resolved DCE data with a combined kinetic deconvolution optical reconstruction (KDOR) method. Multi-distance time-resolved DCE-NIR measurements were made in adult pigs (n=8) during normocapnia, hypocapnia and ischemia. The KDOR method was used to calculate CBF from the DCE-NIR measurements. For validation, CBF was measured independently by CT under each condition. The mean CBF difference between the techniques was -1.7 mL/100 g/min with 95% confidence intervals of -16.3 and 12.9 mL/100 g/min; group regression analysis revealed a strong agreement between the two techniques (slope=1.06±0.08, y-intercept=-4.37±4.33 mL/100 g/min, p<0.001). The results of an error analysis suggest that little a priori information is needed to recover CBF, due to the robustness of the analytical method and the ability of time-resolved NIR to directly characterize the optical properties of the extracerebral tissue (where model mismatch is deleterious). The findings of this study suggest that the DCE-NIR approach presented is a minimally invasive and portable means of determining absolute hemodynamics in neurocritical care patients.