Upper Paleolithic Figurines Showing Women with Obesity may Represent Survival Symbols of Climatic Change.

Figurines of women with obesity or who are pregnant ("Venus figurines") from Upper Paleolithic Europe rank among the earliest art and endured from 38,000 to 14,000 BP (before present), one of the most arduous climatic periods in human history. We propose that the Venus representation relates to human adaptation to climate change. During this period, humans faced advancing glaciers and falling temperatures that led to nutritional stress, regional extinctions, and a reduction in the population. We analyzed Paleolithic figurines of women with obesity to test whether the more obese figurines are from sites during the height of the glacial advance and closer to the glacial fronts. Figurines are less obese as distance from the glaciers increases. Because survival required sufficient nutrition for child-bearing women, we hypothesize that the overnourished woman became an ideal symbol of survival and beauty during episodes of starvation and climate change in Paleolithic Europe.

Evaluation of a point-of-care ultrasound curriculum taught by medical students for physicians, nurses, and midwives in rural Indonesia.

PURPOSE: In the Indonesian health-care system, nurses and midwives often serve as the primary health-care providers due to physician shortages. Seeking to address the need for medical care in resource-limited environments, some have advocated for portable equipment in the hands of health-care providers. We hypothesized that medical students are able to effectively teach point-of-care ultrasound (POCUS) to physicians, nurses, and midwives in rural Indonesia. METHODS: We conducted a prospective, observational study using health-care practitioners from a clinic and accredited school for nursing and midwifery in Mojokerto, East Java, Indonesia. Enrolled practitioners took part in a 4-week POCUS course followed by postinstructional testing. RESULTS: A total of 55 health-care practitioners completed the course. This included 19 physicians, 13 nurses, and 19 midwives. Of the 55 clinicians, 43 (72%) passed the course and 12 (28%) failed. CONCLUSIONS: Physicians, nurses, and midwives in rural Indonesia showed significant acquisition of ultrasound (US) knowledge and skills following a 4-week US course. Following training, all three groups displayed skills in practical US use during a postcourse practical examination. This is one of the first studies to assess the efficacy of medical students teaching POCUS to midwives and nurses.

Artificial intelligence-enabled healthcare delivery.

In recent years, there has been massive progress in artificial intelligence (AI) with the development of deep neural networks, natural language processing, computer vision and robotics. These techniques are now actively being applied in healthcare with many of the health service activities currently being delivered by clinicians and administrators predicted to be taken over by AI in the coming years. However, there has also been exceptional hype about the abilities of AI with a mistaken notion that AI will replace human clinicians altogether. These perspectives are inaccurate, and if a balanced perspective of the limitations and promise of AI is taken, one can gauge which parts of the health system AI can be integrated to make a meaningful impact. The four main areas where AI would have the most influence would be: patient administration, clinical decision support, patient monitoring and healthcare interventions. This health system where AI plays a central role could be termed an AI-enabled or AI-augmented health system. In this article, we discuss how this system can be developed based on a realistic assessment of current AI technologies and predicted developments.

Experiences of Detention under the Mental Health Act for Adults with Anorexia Nervosa.

UNLABELLED: People with Anorexia Nervosa are often resistant to treatment and can be detained under the Mental Health Act. Detention can be distressing for some client groups; however, there is little research to explore how people with Anorexia Nervosa experience detention and how these experiences impact on recovery. This study utilized a qualitative methodology to develop a model for understanding how people perceive, experience and process detention under the Mental Health Act. Data from 12 participants was analysed using constructivist grounded theory. Four overarching categories conceptualize their experience over time: 'the battle', 'the bubble', 'stepping out of the bubble' and 'the anorexic self'. Within each overarching category are further subordinate categories that represent the nuances of the data. The resultant model is discussed in relation to the literature, whilst recommendations have been made to embed person-centred, recovery practice into inpatient services. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: People detained under the mental health act with anorexia nervosa often respond by engaging in a battle with clinicians. This follows by the person withdrawing into a 'bubble' where the individual starts to feel some relief that they are no longer in control of their eating, but this competes with the lack of self and the emerging anorexic self. Clinicians need to be aware that individuals detained may have mixed feelings about their hospital admission.

Biomechanical comparison of frontal plane knee joint moment arms during normal and Tai Chi walking.

[Purpose] Medial knee osteoarthritis, a degenerative joint disease, affects adults. The external knee adduction moment, a surrogate knee-loading measure, has clinical implications for knee osteoarthritis patients. Tai Chi is a promising intervention for pain alleviation in knee osteoarthritis; however, the characteristics of external knee adduction moment during Tai Chi have not been established. [Subjects and Methods] During normal and Tai Chi walking, a gait analysis was performed to compare the external knee adduction moment moment-arm characteristics and paired t-tests to compare moment-arm magnitudes. [Results] A significant difference was observed in the average lateral direction of moment-arm magnitude during Tai Chi walking (-0.0239 ± 0.011 m) compared to that during normal walking (-0.0057 ± 0.004 m). No significant difference was found between conditions in average medial direction of moment-arm magnitude (normal walking: 0.0143 ± 0.010 m; Tai Chi walking: 0.0098 ± 0.014 m). [Conclusion] Tai Chi walking produced a larger peak lateral moment-arm value than normal walking during the stance phase, whereas Tai Chi walking and normal walking peak medial moment-arm values were similar, suggesting that medial knee joint loading may be avoided during Tai Chi walking.

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study.

The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates. 4,724 patients took part in IES, and 206 patients were included in a bone sub-study. BMD and BTM were assessed pre-randomization, during and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12- and 24-month post EOT BMD results are available for 122 and 126 patients, respectively. Similar patient numbers had BTM measured post EOT. Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24 months from EOT, spine BMD increased by 1.53% (95%CI 0.63-2.43; p = 0.001) after stopping exemestane and fell by 1.93% (95%CI -2.91 to 0.95; p = 0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies. Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occurred during exemestane treatment, but fracture rates were similar after treatment withdrawal. With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required.

Randomized controlled trial of ultrasound-guided peripheral intravenous catheter placement versus traditional techniques in difficult-access pediatric patients.

OBJECTIVES: We hypothesized that the use of ultrasound guidance would improve the success rate of peripheral intravenous catheter placement in pediatric patients with difficult access in a pediatric emergency department (ED). Our secondary hypotheses were that ultrasound guidance would reduce the number of attempts, the number of needle redirections, and the overall time to catheter placement. METHODS: This was a prospective randomized study of pediatric ED patients younger than 10 years old requiring intravenous access, presenting between August 2006 and May 2007. Inclusion criteria were 2 unsuccessful traditional attempts at peripheral intravenous access or history of difficult access. Exclusion was critical illness or instability. Patients were randomized to undergo peripheral intravenous catheter placement using continued traditional approaches or real-time, dual-operator ultrasound-guided technique. Measured outcomes were success of cannulation, number of attempts, number of needle redirections, and overall time to catheter placement. RESULTS: Fifty patients were enrolled, with 25 patients randomized to each group. The overall success rates for the ultrasound-guided group were 80% and for the traditional-attempts group, 64%, with a difference in proportions of 16% (95% confidence interval, -9% to 38%, P = 0.208). The ultrasound-guided group required less overall time (6.3 vs 14.4 minutes, difference of -8.1 minutes [95% confidence interval, -12.5 to -3.6], P = 0.001), fewer attempts (median, 1 vs 3; P = 0.004), and fewer needle redirections (median, 2 vs 10; P G 0.0001) than traditional approaches. CONCLUSIONS: In a sample of pediatric ED patients with difficult access, ultrasound-guided intravenous cannulation required less overall time, fewer attempts, and fewer needle redirections than traditional approaches.

Correlation of antecedent stress myocardial perfusion imaging with the infarct related artery in ST-elevation myocardial infarction.

BACKGROUND: While stress myocardial perfusion imaging (MPI) has strong prognostic power, it predicts the site of a subsequent acute myocardial infarction (AMI) in only 47-77% of patients. Prior studies have included small number of subjects and the interval between the stress test and the AMI has varied. The objective of the present study was to further evaluate the relationship between antecedent stress MPI and subsequent AMI. METHODS: We screened 600 patients admitted to our institution with acute ST-elevation MI and identified 21 patients who had a stress MPI an average of 4.8 months prior to the event. The location of perfusion defects on MPI were compared to the angiographic findings at the time of the subsequent AMI. RESULTS: Sixteen patients (76%) with AMI had defects on antecedent stress MPI while 5 patients (24%) had normal scans. Reversible or fixed perfusion defects in the territory corresponding to the site of AMI were seen in 62% of patients. All 5 patients with normal scans had multiple risk factors for coronary artery disease. CONCLUSION: Although a normal stress MPI portends an excellent outcome, a small proportion of patients with normal scans, but with risk factors go on to develop AMI. Stress MPI has reasonable power in predicting future STEMI, but a lesser degree for the location of the future MI. Complementary imaging approaches such as coronary calcium scoring or CT angiography may be beneficial in the assessment of patients at high risk for MI.

Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease.

RATIONALE: Skeletal muscle strength and bulk are reduced in patients with chronic obstructive pulmonary disease (COPD) and influence quality of life, survival, and utilization of health care resources. Exercise training during pulmonary rehabilitation (PR) can reverse some of these effects. In athletes and healthy elderly individuals, dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training, thereby increasing muscle mass. OBJECTIVES: This article examines the effect of CrS on functional exercise capacity and muscle performance in people with COPD. METHODS: One hundred subjects with COPD (mean [SD] age, 68.2 [8.2] yr; FEV(1), 44.0 [19.6] %predicted) were randomized to a double-blind, placebo-controlled, parallel group trial of CrS during 7 weeks of PR encompassing aerobic and resistance exercises. Subjects ingested creatine (22 g/d loading for 5 d; maintenance, 3.76 g/d throughout PR) or placebo. Baseline, postloading, and postrehabilitation measurements included pulmonary function, body composition, peripheral muscle strength, and functional performance (shuttle walking tests). A volunteer subgroup (n = 44) had pre- and postloading quadriceps muscle biopsies. MEASUREMENTS AND MAIN RESULTS: Eighty subjects completed the trial (38 creatine, 42 placebo). All outcome measures significantly improved after PR. There were no significant differences between groups post-PR (mean [SD] change in incremental shuttle walk distance, 84 [79] m in the creatine group vs. 83.8 [60] m in the placebo group; P = 1.0; knee extensor work, 19.2 [16] Nm [Newton meters] in the creatine group vs. 19.5 [17] Nm in the placebo group; P = 0.9). Muscle biopsies showed evidence of creatine uptake. CONCLUSIONS: This adequately powered, randomized, placebo-controlled trial shows that CrS does not augment the substantial training effect of multidisciplinary PR for patients with COPD. Clinical trial registered with https://portal.nihr.ac.uk/Pages/NRRArchiveSearch.aspx (NO123138126).

Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study.

BACKGROUND: Tamoxifen preserves bone in postmenopausal women, but non-steroidal aromatase inhibitors accelerate bone loss and increase fracture risk. We aimed to study the effect on bone health in a subgroup of women included in the Intergroup Exemestane Study (IES), a large randomised trial that compared the switch to the steroidal aromatase inhibitor exemestane with continuation of tamoxifen in the adjuvant treatment of postmenopausal breast cancer. METHODS: Results were analysed from 206 evaluable patients from the IES, in which postmenopausal women with histologically confirmed and completely resected unilateral breast cancer (that was oestrogen-receptor positive or of unknown status), who were disease-free after 2-3 years of treatment with tamoxifen were randomised to continue oral tamoxifen 20 mg/day or switch to oral exemestane 25 mg/day to complete a total of 5 years of adjuvant endocrine therapy. The primary endpoint was change in bone-mineral density (BMD) assessed by dual energy X-ray absorptiometry. Changes in biochemical markers of bone turnover were also analysed in this substudy, and the incidence of fractures in the entire study reported. The IES is registered on the Current Controlled Trials website . FINDINGS: Within 6 months of switching to exemestane, BMD was lowered by 0.051 g/cm(3) (2.7%; 95% CI 2.0-3.4; p<0.0001) at the lumbar spine and 0.025 g/cm(3) (1.4%; 0.8-1.9; p<0.0001) at the hip compared with baseline. BMD decreases were only 1.0% (0.4-1.7; p=0.002) and 0.8% (0.3-1.4; p=0.003) in year 2 at the lumbar spine and hip, respectively. No patient with BMD in the normal range at trial entry developed osteoporosis. Bone resorption and formation markers increased at all time points in women receiving exemestane (p<0.001). With a median follow-up in all IES participants (n=4274) of 58 months, 162 (7%) and 115 (5%) patients in the exemestane and tamoxifen groups, respectively, had fractures (odds ratio 1.45 [1.13-1.87]; p=0.003). INTERPRETATION: These results indicate that the increase in survival shown previously with the IES switch strategy is achieved at the expense of some detriment to skeletal health, so the risk-benefit ratio to women needs to be individually assessed.

Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats.

The carcinogenic potential of human parathyroid hormone 1-84 (PTH) was assessed by daily subcutaneous injection (0, 10, 50, 150 microg/kg/day) for 2 years in Fischer 344 rats. Histopathological analyses were conducted on the standard set of soft tissues, tissues with macroscopic abnormalities, selected bones, and bones with abnormalities identified radiographically. All PTH doses caused widespread osteosclerosis and significant, dose-dependent increases in femoral and vertebral bone mineral content and density. In the mid-and high-dose groups, proliferative changes in bone increased with dose. Osteosarcoma was the most common change, followed by focal osteoblast hyperplasia, osteoblastoma, osteoma and skeletal fibrosarcoma. The incidence of bone neoplasms was comparable in control and low-dose groups providing a noncarcinogenic dose for PTH of 10 microg/kg/day at a systemic exposure to PTH that is 4.6-fold higher than for a 100 microg dose in humans. The ability of PTH to interact with and balance the effects of both the PTH-1 receptor and the putative C-terminal PTH receptor, may lead to the lower carcinogenic potential observed with PTH than reported previously for teriparatide.

Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl.

Calcimimetic compounds, which activate the parathyroid cell Ca(2+) receptor (CaR) and inhibit parathyroid hormone (PTH) secretion, are under experimental study as a treatment for hyperparathyroidism. This report describes the salient pharmacodynamic properties, using several test systems, of a new calcimimetic compound, cinacalcet HCl. Cinacalcet HCl increased the concentration of cytoplasmic Ca(2+) ([Ca(2+)](i)) in human embryonic kidney 293 cells expressing the human parathyroid CaR. Cinacalcet HCl (EC(50) = 51 nM) in the presence of 0.5 mM extracellular Ca(2+) elicited increases in [Ca(2+)](i) in a dose- and calcium-dependent manner. Similarly, in the presence of 0.5 mM extracellular Ca(2+), cinacalcet HCl (IC(50) = 28 nM) produced a concentration-dependent decrease in PTH secretion from cultured bovine parathyroid cells. Using rat medullary thyroid carcinoma 6-23 cells expressing the CaR, cinacalcet HCl (EC(50) = 34 nM) produced a concentration-dependent increase in calcitonin secretion. In vivo studies in rats demonstrated cinacalcet HCl is orally bioavailable and displays approximately linear pharmacokinetics over the dose range of 1 to 36 mg/kg. Furthermore, this compound suppressed serum PTH and blood-ionized Ca(2+) levels and increased serum calcitonin levels in a dose-dependent manner. Cinacalcet was about 30-fold more potent at lowering serum levels of PTH than it was at increasing serum calcitonin levels. The S-enantiomer of cinacalcet (S-AMG 073) was at least 75-fold less active in these assay systems. The present findings provide compelling evidence that cinacalcet HCl is a potent and stereoselective activator of the parathyroid CaR and, as such, might be beneficial in the treatment of hyperparathyroidism.