Evolutionary Patterns of Intersexual Power.

Dominance and leverage are both possible causes of social inequality. If sexual dimorphism influences patterns of intersexual dominance, we predicted that highly dimorphic species are constrained to exhibit male-biased power (MP), but species with low sexual dimorphism are free to demonstrate a broader range of intersexual power relationships. If market effects influence intersexual leverage, we predicted that females have more power when group composition is more male-biased and estrus is asynchronous. We analyzed data on intersexual power, sexual dimorphism, expected estrous overlap, and sex ratio for 79 extant primate species using phylogenetic logistic regression and ancestral state reconstructions. Although MP is more common, every major primate clade includes non-MP species. MP was associated with greater body mass and canine length dimorphism and with female-biased sex-ratios. Low estrous overlap was associated with non-MP. Although MP was reconstructed as likely ancestral for anthropoids, the last common ancestor of this clade probably did not exhibit high sexual dimorphism. The last common ancestor of catarrhines was probably highly dimorphic, potentially constraining intersexual power relationships. Non-MP probably evolved multiple times in primates and may be less common because multiple traits are linked to MP while fewer traits are associated with female-biased power or equality.

Prevalence of and Factors Associated with Gabapentinoid Use and Misuse Among Texas Medicaid Recipients.

BACKGROUND AND OBJECTIVES: Gabapentin and pregabalin have been considered relatively safe opioid-sparing adjuncts for pain management. However, rising prescribing trends, presence of gabapentinoids in opioid-related overdoses, and the growing body of evidence regarding gabapentinoid misuse and abuse, have caused gabapentinoids to emerge as a drug class of public health concern. This study aimed to assess the prevalence of, and factors associated with gabapentinoid use and misuse. METHODS: This retrospective study of Texas Medicaid data from 1/1/2012 to 30/8/2016 included patients aged 18-63 years at index date, with ≥ 1 gabapentinoid prescription, and continuously enrolled 6 months pre-index and 12 months post-index. Gabapentinoid misuse was defined as ≥ 3 claims exceeding daily doses of 3600 mg for gabapentin and 600 mg for pregabalin. Age, gender, concurrent opioid use, neuropathic pain diagnoses and gabapentinoid type were independent variables. Descriptive and inferential statistics were used. RESULTS: Of included subjects (N = 39,000), 0.2% (N = 81) met study criteria for gabapentinoid misuse. Overall, the majority (76.4%) of gabapentinoid users were aged 41-63 years with a mean ± SD age of 48.2 ± 10.7 years. Those patients meeting the study criteria for gabapentinoid misuse were significantly younger (45.1 ± 11.0 vs 48.2 ± 10.7, p = 0.0084). Majority of the study sample was female (68.1%). However, a significantly higher proportion of males met the study criteria for gabapentinoid misuse compared to females (0.3% vs 0.2%, p = 0.0079). Approximately one-half (51.9%) of the study sample had neuropathic pain, and gabapentinoid misuse was significantly higher in neuropathic pain patients compared to those without neuropathic pain (0.3% vs 0.1%, p = 0.0078). Over three-quarters (77.4%) of patients were using gabapentin; however, gabapentinoid misuse was significantly higher among pregabalin users (0.4% vs 0.2%, p = 0.0003). Approximately 20% (17.3%) of gabapentinoid users had ≥ 90 days of concurrent opioid use. However, there was no significant difference in gabapentinoid misuse among patients with concurrent opioid use compared to patients without (0.3% vs 0.2%, p = 0.1440). Factors significantly associated with misuse included: male sex (odds ratio [OR] 0.486; 95% confidence interval [CI] 0.313-0.756; p = 0.0013); neuropathic pain (OR 2.065; 95% CI 1.289-3.308; p = 0.0026); and pregabalin versus gabapentin use (OR 2.337, 95% CI 1.492-3.661; p = 0.0002). Concurrent opioid use was not significantly associated with gabapentinoid misuse (OR 1.542, 95% CI 0.920-2.586; p = 0.1006). CONCLUSION: Prevalence of gabapentinoid misuse was low (0.2%) among Texas Medicaid recipients. Younger age, male gender, neuropathic pain diagnosis and pregabalin use were significantly associated with higher levels of gabapentinoid misuse.

Stop the Bleed: An Interprofessional Community Service Learning Project Assessing the Efficacy of Pharmacist-Led Hemorrhage Control Education for Laypersons.

OBJECTIVES: Stop the Bleed (STB) is a national initiative that provides lifesaving hemorrhagic control education. In 2019, pharmacists were added as health-care personnel eligible to become STB instructors. This study was conducted to evaluate the efficacy of pharmacist-led STB trainings for school employees in South Texas. METHODS: Pharmacist-led STB trainings were provided to teachers and staff in Laredo, Texas. The 60-min trainings included a presentation followed by hands-on practice of tourniquet application, wound-packing, and direct pressure application. Training efficacy was assessed through anonymous pre- and postevent surveys, which evaluated changes in knowledge, comfort level, and willingness to assist in hemorrhage control interventions. Student volunteers (predominantly pharmacy and medical students) assisted in leading the hands-on portion, providing a unique interprofessional learning opportunity. RESULTS: Participants with previous training (N = 98) were excluded, resulting in a final cohort of 437 (response rate 87.4%). Compared with baseline, comfort level using tourniquets (mean, 3.17/5 vs 4.20/5; P < 0.0001), opinion regarding tourniquet safety (2.59/3 vs 2.94/3; P < 0.0001), and knowledge regarding tourniquets (70.86/100 vs 75.84/100; P < 0.0001) and proper tourniquet placement (2.40/4 vs 3.15/4; P < 0.0001) significantly improved. CONCLUSIONS: Pharmacist-led STB trainings are efficacious in increasing school worker knowledge and willingness to respond in an emergency hemorrhagic situation.

Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in Texas, USA.

BACKGROUND AND AIMS: Patients with opioid use disorder (OUD) must be able to obtain prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) from a pharmacy promptly to reduce risk for a recurrence of use and subsequent morbidity and mortality. Telephone audits have identified concerning gaps in availability of NNS within US pharmacies, but the availability of BUP/NX has not been rigorously evaluated. This study estimated the availability of BUP/NX and NNS in the US state of Texas and compared availability by pharmacy type and metropolitan status. DESIGN: A cross-sectional telephone audit with a secret shopper approach conducted from 18 May 2020 to 7 June 2020. Setting and Participants A random sample of 800 of 5078 (16%) community pharmacies licensed with the Texas State Board of Pharmacy. MEASUREMENTS: Primary outcomes included availability of a 1-week supply of generic BUP/NX 8/2 mg films and a single unit of NNS 4 mg, overall and by pharmacy type. Secondary outcomes included willingness and estimated time-frame to order BUP/NX if unavailable. FINDINGS: Data from 704 pharmacies (471 chain, 233 independent) were included for analyses. Of these, 34.1% of pharmacies (45.0% of chains versus 12.0% of independents, P < 0.0001) were willing and able to dispense a 1-week supply of generic BUP/NX and a single unit of NNS. BUP/NX alone was available in 42.2% of pharmacies (52.4% of chains versus 21.5% of independents, P < 0.0001). NNS alone was available in 60.1% of pharmacies (77.9% of chains versus 24.0% of independents, P < 0.0001). Of the 397 pharmacies with generic BUP/NX unavailable, 62.2% of pharmacies (73.9% of chains versus 48.0% of independents, P < 0.0001) indicated willingness to order. CONCLUSIONS: Most pharmacies in Texas do not appear to be willing and able to dispense prescribed buprenorphine/naloxone films and naloxone nasal spray to patients with opioid use disorder in a timely manner. Deficiencies in availability are markedly more pronounced in independent pharmacies compared with chain pharmacies.

Pharmacists are missing an opportunity to save lives and advance the profession by embracing opioid harm reduction.

More than 70,000 Americans died as a result of a drug overdose in 2017, and a substantial majority of those deaths involved an opioid. Supply-reduction interventions, such as prescription monitoring programs, tamper-resistant formulations, and prescribing limits have failed to reverse rising rates of opioid-related morbidity and mortality. Instead, they may be contributing to this trend by forcing people with opioid use disorder to an increasingly potent illicit market with scant resources for sterile injection. Pharmacists are recognized by governmental authorities, public health experts, and other health professionals as key partners in opioid harm reduction. This is reflected by the proliferation of state laws supporting pharmacy-based access to naloxone, an opioid antagonist that can rapidly reverse the effects of an opioid overdose. Expanded authority to distribute naloxone without an outside prescription, coupled with the provision of sterile syringes and evidence-based medications for opioid use disorder, represents a powerful opportunity for pharmacists to save lives while advancing the role of the profession. However, numerous studies have documented a lack of readiness among pharmacists to dispense naloxone and little willingness to provide sterile syringes. As a profession, it is imperative that we ensure all pharmacists receive adequate education regarding opioid harm reduction interventions and ongoing support to implement these interventions within their practices.

Telehealth Impact on Primary Care Related Ambulance Transports.

Introduction: Telehealth has been used nominally for trauma, neurological, and cardiovascular incidents in prehospital emergency medical services (EMS). Yet, much less is known about the use of telehealth for low-acuity primary care. We examine the development of one telehealth program and its impact on unnecessary ambulance transports. Objective: The objective of this study is to describe the development and impact of a large-scale telehealth program on ambulance transports. Methods: We describe the patient characteristics and results from a cohort of patients in Houston, Texas who received a prehospital telehealth consultation from an emergency medicine physician. Inclusion criteria were adults and pediatric patients with complaints considered to be non-urgent, primary care related. Data were analyzed for 36 months, from January 2015 through December 2017. Our primary dependent variable was the percentage of patients transported by ambulance. We used descriptive statistics to describe patient demographics, chi-square to examine differences between groups, and logistic regression to explore the effects with multivariate controls including age, gender, race, and chief complaint. Results: A total of 15,067 patients were enrolled (53% female; average age 44 years ± 19 years) over the three-year period. The 3 primary chief complaints were based on abdominal pains (13% of cases), nausea/vomiting/diarrhea (NVD) (9.4%), and back pain (9.3%). Ambulance transports represented 11.2% of all transports in the program, while alternative taxi transportation was used in 75.6%, and the remainder were self- or no-transports. Taxi transportation to an alternate, affiliated clinic (versus ED) was utilized in 5% of incidents. After multivariate controls, older age patients presenting with low-risk, non-acute chest pain, shortness of breath, and dizziness were much more likely to use ambulance transport. Race and gender were not significant predictors of ambulance transport. Conclusions: We found telehealth offers a technology strategy to address potentially unnecessary ambulance transports. Based on prior cost-effectiveness analyses, the reduction of unnecessary ambulance transports translates to an overall reduction in EMS agency costs. Telehealth programs offer a viable solution to support alternate destination and alternate transport programs.

Hit-to-Lead: Hit Validation and Assessment.

High-throughput screening assays have become nearly ubiquitous in the search for small compounds or peptides that can modulate biological processes for therapeutic purposes. While many assays have become quite robust, with well-established protocols, the subsequent steps of validating the hits and choosing the best ones to take forward into leads for further chemical development are less established. In this chapter, we describe a variety of approaches, including chemical assessment, the use of various computational approaches, a variety of counter-screens, and "orthogonal" biophysical assays using nuclear magnetic resonance, surface plasmon resonance, isothermal titration calorimetry or thermal shift assays as methods for validating and assessing the quality of hits.

Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?

Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses.

An assessment of the information content of likelihood ratios derived from complex mixtures.

With the increasing sensitivity of DNA typing methodologies, as well as increasing awareness by law enforcement of the perceived capabilities of DNA typing, complex mixtures consisting of DNA from two or more contributors are increasingly being encountered. However, insufficient research has been conducted to characterize the ability to distinguish a true contributor (TC) from a known non-contributor (KNC) in these complex samples, and under what specific conditions. In order to investigate this question, sets of six 15-locus Caucasian genotype profiles were simulated and used to create mixtures containing 2-5 contributors. Likelihood ratios were computed for various situations, including varying numbers of contributors and unknowns in the evidence profile, as well as comparisons of the evidence profile to TCs and KNCs. This work was intended to illustrate the best-case scenario, in which all alleles from the TC were detected in the simulated evidence samples. Therefore the possibility of drop-out was not modeled in this study. The computer program DNAMIX was then used to compute LRs comparing the evidence profile to TCs and KNCs. This resulted in 140,000 LRs for each of the two scenarios. These complex mixture simulations show that, even when all alleles are detected (i.e. no drop-out), TCs can generate LRs less than 1 across a 15-locus profile. However, this outcome was rare, 7 of 140,000 replicates (0.005%), and associated only with mixtures comprising 5 contributors in which the numerator hypothesis includes one or more unknown contributors. For KNCs, LRs were found to be greater than 1 in a small number of replicates (75 of 140,000 replicates, or 0.05%). These replicates were limited to 4 and 5 person mixtures with 1 or more unknowns in the numerator. Only 5 of these 75 replicates (0.004%) yielded an LR greater than 1,000. Thus, overall, these results imply that the weight of evidence that can be derived from complex mixtures containing up to 5 contributors, under a scenario in which no drop-out is required to explain any of the contributors, is remarkably high. This is a useful benchmark result on top of which to layer the effects of additional factors, such as drop-out, peak height, and other variables.

The fate of grafting acetabular defects during revision total hip arthroplasty.

BACKGROUND: Acetabular defects are frequently grafted during revision THA. Previous studies using plain radiographs report high rates of graft incorporation. However, given plain radiographs underestimate osteolysis, it is unclear whether plain radiographs adequately reflect graft fill or incorporation. QUESTIONS/PURPOSES: We determined if (1) graft fill; or (2) incorporation (measured as graft-bone contact) differed with complete revision and grafting compared to liner exchange and grafting; (3) defect fill and incorporation could be assessed on plain radiographs; and (4) the cost of bone grafting differed with these two procedures. METHODS: We identified 40 patients who underwent revision THA for aseptic loosening or polyethylene wear and osteolysis, either with retention of a well-fixed cup or complete acetabular revision in which bone graft was used. Lesion size, percent fill, and graft healing was quantified from CT scans. A limited cost analysis was performed using the current hospital costs for implants, bone grafts, and bone graft substitutes. The minimum followup was 1 year (mean, 4.8 years; range, 1-11 years). RESULTS: The average defect fill was 30% (range, 0%-81%). The average percent of healing to host bone was 24% (range, 0-66%). Complete revisions had a higher percent defect fill compared to head/liner changes (47% versus 17%) as well as a higher degree of graft healing to host bone compared to head/liner changes (36% versus 14%). High resolution CT demonstrated lower percentages of defect fill and graft healing than previous reports based on plain radiographs. Bone grafting costs exceeded implant costs in the head/liner exchange group; however, the overall cost was higher in the complete revision group. CONCLUSIONS: Higher degrees of defect fill and healing were seen with complete revisions compared to head/liner exchanges. Compared to CT scans, plain radiograph assessment tended to overestimate defect fill and healing.

Correlation of computed tomography with histology in the assessment of periprosthetic defect healing.

Computed tomography (CT) may more accurately assess the healing of grafted osteolytic lesions around acetabular components compared with plain radiographs, although clinical validation is lacking. To determine whether clinical or micro-CT imaging could assess accurately the grafted lesion compared with histology, we therefore quantified bone healing and ingrowth to determine an effective rhBMP-2 dose and ratio to allograft bone when grafted adjacent to a cementless porous-coated component. We grafted surgically created acetabular defects in canines (n = 20) before uncemented total hip arthroplasty. At 6 weeks, embedded acetabula were imaged and the CT slice images matched to histology section images. The percentage of bone in the defect and growth into the porous surface was assessed quantitatively. Low-dose rhBMP-2 with allograft (1:5 ratio) resulted in a higher percentage of defect healing (43.8%) than rhBMP-2 alone (29.2%) and a higher percentage of bone ingrowth (15.7%) than allograft bone alone (1.1%) as measured by histology. Micro-CT measurements were similar to histologic measurements of defect healing, whereas clinical CT overestimated periprosthetic bone by 38%. Neither clinical CT nor micro-CT techniques are adequate for assessing ingrowth or the bone-implant interface with metal artifacts.

Functional linear discriminant analysis: a new longitudinal approach to the assessment of embryonic growth.

BACKGROUND: Functional linear discriminant analysis (FLDA) is a new growth assessment technique using serial measurements to discriminate between normal and abnormal fetal growth. We used FLDA to assess and compare growth in live pregnancies destined to miscarry with those remaining viable. METHODS: This was a prospective cohort study of women with ultrasound scans on at least two separate occasions showing live pregnancies. Serial crown-rump length (CRL), mean gestational sac diameter and mean yolk sac diameter measurements were recorded. The ability of FLDA to predict subsequent miscarriage was compared with that of a single CRL measurement. RESULTS: Of 521 included pregnancies, 493 (94.6%) remained viable at 14 weeks and 28 (5.4%) miscarried. The CRL growth rate was significantly lower in those that miscarried (one-sample t-test, P = 2.638E-22). The sensitivity of FLDA in predicting miscarriage from serial CRL measurements was 60.7% and specificity was 93.1% [positive predictive value (PPV) 33.3%, negative predictive value (NPV) 97.7%]. This was significantly better for predicting miscarriage than a single CRL observation of more than 2SD below that expected (sensitivity 53.6%, specificity 72.2%, PPV 9.9%, NPV 96.5%). CONCLUSIONS: FLDA discriminates between normal and abnormal growth to predict miscarriage with high specificity. FLDA predicts miscarriage better than a single observation of a small CRL.

Reliability and validity of combined imaging and pressures assessment methods for diabetic feet.

OBJECTIVES: To determine the reliability of using 3-dimensional (3D) spiral x-ray computed tomography (SXCT) imaging methods to measure anatomic foot structure and to test the validity of using a loading device to simulate walking pressures on the plantar foot during SXCT examination. DESIGN: Nonrandomized control trial of consecutive patients with complete data compared with age-matched controls. SETTING: A clinical SXCT scanner and physical therapy laboratory in a local hospital. PARTICIPANTS: Eight subjects with diabetes and a history of forefoot ulcers and 8 control subjects. INTERVENTIONS: SXCT imaging and plantar pressure analysis were used to acquire 3D volumetric structure and pressure data of the foot during 4 foot positions, 2 weight bearing and 2 non-weight bearing. MAIN OUTCOME MEASURES: Differences between repeated SXCT measures of foot structure. Comparisons of plantar foot pressure. Foot structure measurements. Methods for measuring the bony angles and soft-tissue thickness were developed and reliability tests were performed. RESULTS: There was essentially no bias (<+/-0.5mm or +/-0.5 degrees ) and a high degree of reliability (81% of the measures had a reliability <2.0mm or 2 degrees ) when measuring foot structures. Correlations of pressure measures collected on the loading device compared with those collected during walking were (mean +/- standard deviation) r =.66 +/-.06. The percentage agreement between the pressures collected on the loading device and during walking was 91.1% +/- 4.7%. CONCLUSION: Reliability of anatomic foot structure measurements and validity of plantar loading during visualization were good. These methods may be used to determine structural differences between diabetic and healthy feet and to evaluate how these differences relate to plantar pressures.

Prioritization of health care services. A progress report by the Oregon Health Services Commission.

The Oregon Health Services Commission is composed of a group of 11 consumers and health care professionals. It was appointed by the governor as required by the "Oregon Basic Health Services Act" to produce a prioritized list of health services ranked on the basis of their relative importance to populations served. Following actuarial analysis, the legislature will determine the extent to which the "list" of services can be funded to provide health care access for Medicaid recipients earning up to the 100th percentile of the federal poverty level. Prioritization will be based on a cost-benefit formula applied to each treatment/condition unit and assignment of each of these to a general category, which itself has been ranked on the basis of "public value."

Design of dental equipment for remote rural and field areas.

In the context of providing dental services, remote areas may be defined as those with overall low population densities; or isolated areas of low population density within more populous regions; or areas of high population density remote from dental services. The provision of equipment for remote areas is not simply a matter of extending the supply of conventional operatories to these regions. The particular needs of a region must be assessed first with equipment and instruments being selected to serve the skills of personnel who can be trained locally. The preventive-surface care operatory is the most basic yet most widely usable operatory. Staffed by auxiliary personnel it will facilitate communication, primary care procedures and the completion of non-invasive tasks. The design of operatories to a preferred work position will simplify the design of fixed installations and associated equipment and overall costs will be reduced. New educational methodologies will influence the design and manufacture of equipment more than in the past. For remote areas there are physical and practical limitations to equipment design but the preferred work position should not be compromised. If this is maintained the transfer of skills between different work places is simplified and mobilization of the operatory is facilitated.