A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.

In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:

Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters.

Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology.

Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of the MSY derives from the ancestral autosomes that gave rise to the mammalian sex chromosomes. Instead, all but 45 of the MSY's genes belong to three acquired, massively amplified gene families that have no homologs on primate MSYs but do have acquired, amplified homologs on the mouse X chromosome. The complete mouse MSY sequence brings to light dramatic forces in sex chromosome evolution: lineage-specific convergent acquisition and amplification of X-Y gene families, possibly fueled by antagonism between acquired X-Y homologs. The mouse MSY sequence presents opportunities for experimental studies of a sex-specific chromosome in its entirety, in a genetically tractable model organism.

A metabolic pathway for bile acid dehydroxylation by the gut microbiome.

The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 µM and are known to block the growth of Clostridium difficile1, promote hepatocellular carcinoma2 and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref. 3). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.

Mitochondrial respiration is lower in the intrauterine growth-restricted fetal sheep heart.

Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth-restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1-3, LeakOmy, and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI-CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment. KEY POINTS: Growth-restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood. Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids. We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed. Our data show that the mitochondria respiration levels in the growth-restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified. These results indicate an impaired metabolic maturation of the growth-restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally.

Steric Control of Luminescence in Phenyl-Substituted Trityl Radicals.

Triphenylmethyl (trityl) radicals have shown potential for use in organic optoelectronic applications, but the design of practical trityl structures has been limited to donor/radical charge-transfer systems due to the poor luminescence of alternant symmetry hydrocarbons. Here, we circumvent the symmetry-forbidden transition of alternant hydrocarbons via excited-state symmetry breaking in a series of phenyl-substituted tris(2,4,6-trichlorophenyl)methyl (TTM) radicals. We show that 3-fold phenyl substitution enhances the emission of the TTM radical and that steric control modulates the optical properties in these systems. Simple ortho-methylphenyl substitution boosts the photoluminescence quantum efficiency from 1% (for TTM) to 65% at a peak wavelength of 612 nm (for 2-T3TTM) in solution. In the crystalline solid state, the neat 2-T3TTM radical shows a remarkably high photoluminescence quantum efficiency of 25% for emission peaking at 706 nm. This has implications in the design of aryl-substituted radical structures where the electronic coupling of the substituents influences variables such as emission, charge transfer, and spin interaction.

Diagnostic Adjunct Techniques in the Assessment of Hypovolemia: A Prospective Pilot Project.

INTRODUCTION: Measuring the hypovolemic resuscitation end point remains a critical care challenge. Our project compared clinical hypovolemia (CH) with three diagnostic adjuncts: 1) noninvasive cardiac output monitoring (NICOM), 2) ultrasound (US) static IVC collapsibility (US-IVC), and 3) US dynamic carotid upstroke velocity (US-C). We hypothesized US measures would correlate more closely to CH than NICOM. METHODS: Adult trauma/surgical intensive care unit patients were prospectively screened for suspected hypovolemia after acute resuscitation, excluding patients with burns, known heart failure, or severe liver/kidney disease. Adjunct measurements were assessed up to twice a day until clinical improvement. Hypovolemia was defined as: 1) NICOM: ≥10% stroke volume variation with passive leg raise, 2) US-IVC: <2.1 cm and >50% collapsibility (nonventilated) or >18% collapsibility (ventilated), 3) US-C: peak systolic velocity increase 15 cm/s with passive leg raise. Previously unknown cardiac dysfunction seen on US was noted. Observation-level data were analyzed with a Cohen's kappa (κ). RESULTS: 44 patients (62% male, median age 60) yielded 65 measures. Positive agreement with CH was 47% for NICOM, 37% for US-IVC and 10% for US-C. None of the three adjuncts correlated with CH (κ -0.045 to 0.029). After adjusting for previously unknown cardiac dysfunction present in 10 patients, no adjuncts correlated with CH (κ -0.036 to 0.031). No technique correlated with any other (κ -0.118 to 0.083). CONCLUSIONS: None of the adjunct measurements correlated with CH or each other, highlighting that fluid status assessment remains challenging in critical care. US should assess for right ventricular dysfunction prior to resuscitation.

Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes.

Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) chromosomes formed by homologous crossing over between opposing arms of palindromes on sister chromatids. These ectopic recombination events occur at nearly all Y-linked palindromes. Based on our findings, we propose that intrapalindrome sequence identity is maintained via noncrossover pathways of homologous recombination. DNA double-strand breaks that initiate these pathways can be alternatively resolved by crossing over between sister chromatids to form idicY chromosomes, with clinical consequences ranging from spermatogenic failure to sex reversal and Turner syndrome. Our observations imply that crossover and noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes.

Adaptive responses in uteroplacental metabolism and fetoplacental nutrient shuttling and sensing during placental insufficiency.

Glucose, lactate, and amino acids are major fetal nutrients. During placental insufficiency-induced intrauterine growth restriction (PI-IUGR), uteroplacental weight-specific oxygen consumption rates are maintained, yet fetal glucose and amino acid supply is decreased and fetal lactate concentrations are increased. We hypothesized that uteroplacental metabolism adapts to PI-IUGR by altering nutrient allocation to maintain oxidative metabolism. Here, we measured nutrient flux rates, with a focus on nutrients shuttled between the placenta and fetus (lactate-pyruvate, glutamine-glutamate, and glycine-serine) in a sheep model of PI-IUGR. PI-IUGR fetuses weighed 40% less and had decreased oxygen, glucose, and amino acid concentrations and increased lactate and pyruvate versus control (CON) fetuses. Uteroplacental weight-specific rates of oxygen, glucose, lactate, and pyruvate uptake were similar. In PI-IUGR, fetal glucose uptake was decreased and pyruvate output was increased. In PI-IUGR placental tissue, pyruvate dehydrogenase (PDH) phosphorylation was decreased and PDH activity was increased. Uteroplacental glutamine output to the fetus and expression of genes regulating glutamine-glutamate metabolism were lower in PI-IUGR. Fetal glycine uptake was lower in PI-IUGR, with no differences in uteroplacental glycine or serine flux. These results suggest increased placental utilization of pyruvate from the fetus, without higher maternal glucose utilization, and lower fetoplacental amino acid shuttling during PI-IUGR. Mechanistically, AMP-activated protein kinase (AMPK) activation was higher and associated with thiobarbituric acid-reactive substances (TBARS) content, a marker of oxidative stress, and PDH activity in the PI-IUGR placenta, supporting a potential link between oxidative stress, AMPK, and pyruvate utilization. These differences in fetoplacental nutrient sensing and shuttling may represent adaptive strategies enabling the placenta to maintain oxidative metabolism.NEW & NOTEWORTHY These results suggest increased placental utilization of pyruvate from the fetus, without higher maternal glucose uptake, and lower amino acid shuttling in the placental insufficiency-induced intrauterine growth restriction (PI-IUGR) placenta. AMPK activation was associated with oxidative stress and PDH activity, supporting a putative link between oxidative stress, AMPK, and pyruvate utilization. These differences in fetoplacental nutrient sensing and shuttling may represent adaptive strategies enabling the placenta to maintain oxidative metabolism at the expense of fetal growth.

Sequence analysis in Bos taurus reveals pervasiveness of X-Y arms races in mammalian lineages.

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X-Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X-Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.

Chronic Fetal Leucine Infusion Increases Rate of Leucine Oxidation but Not of Protein Synthesis in Late Gestation Fetal Sheep.

BACKGROUND: Leucine increases protein synthesis rates in postnatal animals and adults. Whether supplemental leucine has similar effects in the fetus has not been determined. OBJECTIVE: To determine the effect of a chronic leucine infusion on whole-body leucine oxidation and protein metabolic rates, muscle mass, and regulators of muscle protein synthesis in late gestation fetal sheep. METHODS: Catheterized fetal sheep at ∼126 d of gestation (term = 147 d) received infusions of saline (CON, n = 11) or leucine (LEU; n = 9) adjusted to increase fetal plasma leucine concentrations by 50%-100% for 9 d. Umbilical substrate net uptake rates and protein metabolic rates were determined using a 1-13C leucine tracer. Myofiber myosin heavy chain (MHC) type and area, expression of amino acid transporters, and abundance of protein synthesis regulators were measured in fetal skeletal muscle. Groups were compared using unpaired t tests. RESULTS: Plasma leucine concentrations were 75% higher in LEU fetuses compared with CON by the end of the infusion period (P < 0.0001). Umbilical blood flow and uptake rates of most amino acids, lactate, and oxygen were similar between groups. Fetal whole-body leucine oxidation was 90% higher in LEU (P < 0.0005) but protein synthesis and breakdown rates were similar. Fetal and muscle weights and myofiber areas were similar between groups, however, there were fewer MHC type IIa fibers (P < 0.05), greater mRNA expression levels of amino acid transporters (P < 0.01), and a higher abundance of signaling proteins that regulate protein synthesis (P < 0.05) in muscle from LEU fetuses. CONCLUSIONS: A direct leucine infusion for 9 d in late gestation fetal sheep does not increase protein synthesis rates but results in higher leucine oxidation rates and fewer glycolytic myofibers. Increasing leucine concentrations in the fetus stimulates its own oxidation but also increases amino acid transporter expression and primes protein synthetic pathways in skeletal muscle.

Changes in microvascular perfusion of heart and skeletal muscle in sheep around the time of birth.

NEW FINDINGS: What is the central question of this study? How does the microvascular perfusion of striated muscle change during the dynamic developmental period between the late gestation fetus and early neonate? What is the main finding and its importance? In both myocardium and skeletal muscle, perfusion of striated muscle is significantly reduced in the neonate compared to the late term fetus, but flow reserve is unchanged. The results suggest striated muscle capillary networks grow more slowly relative to the myofibres they nourish during the perinatal period. ABSTRACT: Microvascular perfusion of striated muscle is an important determinant of health throughout life. Birth is a transition with profound effects on the growth and function of striated muscle, but the regulation of microvascular perfusion around this transition is poorly understood. We used contrast-enhanced ultrasound perfusion imaging (CEUS) to study the perfusion of left ventricular myocardium and hindlimb biceps femoris, which are populations of muscle with different degrees of change in pre- to postnatal workloads and different capacities for postnatal proliferative growth. We studied separate groups of lambs in late gestation (135 days' gestational age; 92% of term) and shortly after birth (5 days' postnatal age). We used CEUS to quantify baseline perfusion, perfusion during hyperaemia induced by adenosine infusion (myocardium) or electrically stimulated unloaded exercise (skeletal muscle), flow reserve and oxygen delivery. We found heart-to-body weight ratio was greater in neonates than fetuses. Microvascular volume and overall perfusion were lower in neonates than fetuses in both muscle groups at baseline and with hyperaemia. Flux rate differed with muscle group, with myocardial flux being faster in neonates than fetuses, but skeletal muscle flux being slower. Oxygen delivery to skeletal muscle at baseline was lower in neonates than fetuses, but was not significantly different in myocardium. Flow reserve was not different between ages. Given the significant somatic growth, and the transition from hyperplastic to hypertrophic myocyte growth occurring in the perinatal period, we postulate that the primary driver of lower neonatal striated muscle perfusion is faster growth of myofibres than their associated capillary networks.

What If We Do Not Operate? Outcomes of Nonoperatively Managed Emergency General Surgery Patients.

INTRODUCTION: Although two-thirds of patients with emergency general surgery (EGS) conditions are managed nonoperatively, their long-term outcomes are not well described. We describe outcomes of nonoperative management in a cohort of older EGS patients and estimate the projected risk of operative management using the NSQIP Surgical Risk Calculator (SRC). MATERIALS AND METHODS: We studied single-center inpatients aged 65 y and more with an EGS consult who did not undergo an operation (January 2019-December 2020). For each patient, we recorded the surgeon's recommendation as either an operation was "Not Needed" (medical management preferred) or "Not Recommended" (risk outweighed benefits). Our main outcome of interest was mortality at 30 d and 1 y. Our secondary outcome of interest was SRC-projected 30-day postoperative mortality risk (median % [interquartile range]), calculated using hypothetical low-risk and high-risk operations. RESULTS: We included 204 patients (60% female, median age 75 y), for whom an operation was "Not Needed" in 81% and "Not Recommended" in 19%. In this cohort, 11% died at 30 d and 23% died at 1 y. Mortality was higher for the "Not Recommended" cohort (37% versus 5% at 30 d and 53% versus 16% at 1 y, P < 0.05). The SRC-projected 30-day postoperative mortality risk was 3.7% (1.3-8.7) for low-risk and 5.8% (2-11.8) for high-risk operations. CONCLUSIONS: Nonoperative management in older EGS patients is associated with very high risk of short-term and long-term mortality, particularly if a surgeon advised that risks of surgery outweighed benefits. The SRC may underestimate risk in the highest-risk patients.

Development of Imaging Criteria for Geriatric Blunt Trauma Patients.

INTRODUCTION: Current decision tools to guide trauma computed tomography (CT) imaging were not validated for use in older patients. We hypothesized that specific clinical variables would be predictive of injury and could be used to guide imaging in this population to minimize risk of missed injury. METHODS: Blunt trauma patients aged 65 y and more admitted to a Level 1 trauma center intensive care unit from January 2018 to November 2020 were reviewed for histories, physical examination findings, and demographic information known at the time of presentation. Injuries were defined using the patient's final abbreviated injury score codes, obtained from the trauma registry. Abbreviated injury score codes were categorized by corresponding CT body region: Head, Face, Chest, C-Spine, Abdomen/Pelvis, or T/L-Spine. Variable groupings strongly predictive of injury were tested to identify models with high sensitivity and a negative predictive value. RESULTS: We included 608 patients. Median age was 77 y (interquartile range, 70-84.5) and 55% were male. Ground-level fall was the most common injury mechanism. The most commonly injured CT body regions were Head (52%) and Chest (42%). Variable groupings predictive of injury were identified in all body regions. We identified models with 97.8% sensitivity for Head and 98.8% for Face injuries. Sensitivities more than 90% were reached for all except C-Spine and Abdomen/Pelvis. CONCLUSIONS: Decision aids to guide imaging for older trauma patients are needed to improve consistency and quality of care. We have identified groupings of clinical variables that are predictive of injury to guide CT imaging after geriatric blunt trauma. Further study is needed to refine and validate these models.

Characteristics associated with successful foodborne outbreak investigations involving United States retail food establishments (2014-2016).

This study examined relationships between foodborne outbreak investigation characteristics, such as the epidemiological methods used, and the success of the investigation, as determined by whether the investigation identified an outbreak agent (i.e. pathogen), food item and contributing factor. This study used data from the Centers for Disease Control and Prevention's (CDC) National Outbreak Reporting System and National Environmental Assessment Reporting System to identify outbreak investigation characteristics associated with outbreak investigation success. We identified investigation characteristics that increase the probability of successful outbreak investigations: a rigorous epidemiology investigation method; a thorough environmental assessment, as measured by number of visits to complete the assessment; and the collection of clinical samples. This research highlights the importance of a comprehensive outbreak investigation, which includes epidemiology, environmental health and laboratory personnel working together to solve the outbreak.

Assessing essential service provision for prevention and management of violence against women in a remote indigenous community in Amantaní, Peru.

BACKGROUND: Women living in indigenous communities in Peru currently experience extremely high rates of intimate partner violence (IPV). Over the past 10 years, there has been a large multi-sectoral initiative to establish a national network of Centros de Emergencia de la Mujer (Women's Emergency Centres) that integrate health and police services, and substantial increase in efforts from non-governmental organisations in supporting survivors of violence. However, there is currently little evidence on how existing services meet the needs of indigenous women experiencing violence in Peru. METHODS: As part of a broader mixed-methods participatory VAWG prevention study, we assessed existing service provision for women experiencing violence in an indigenous Quechua community from Amantaní, Peru. This involved 17 key informant interviews with legal, government, police, and civil society representatives. We used the UN Women Essential Services Package for Women and Girls Subject to Violence framework to guide our analysis. RESULTS: Participants identified major gaps in existing services for indigenous women survivors of violence in Peru. They discussed survivors and perpetrators not being identified by the health system, a lack of IPV response training for health professionals, IPV not being prioritised as a health concern, and a lack of health services that are culturally appropriate for indigenous populations. Survivors who report to police are often treated poorly and discriminated against. Legal systems were perceived as insufficient and ineffective, with inadequate legal measures for perpetrators. While legal and policy frameworks exist, they are often not applied in practice. Service provision in this region needs to adopt an intercultural, rights based, gendered approach to IPV response and prevention, considering cultural and linguistic relevance for indigenous populations. CONCLUSION: The role of structural violence in perpetuating indigenous women's experiences of violence and undermining their access to services must be central to designing and implementing appropriate policies and services if they are to meet the needs of indigenous women in Peru.

Quantification of fragmentation capture materials and an assessment of the viability of economical alternatives: a preliminary study.

High pressure, high-temperature events need to be quantified experimentally. Where fragmentation occurs, i.e. against personal protective equipment, there is a requirement for both a reliable and repeatable measurement of numerous experimental metrics. Typically, the most critical is calculating the energy absorbed by the target material, to characterize target performance. This is achieved by detonating a device and capturing a proportion of the fragmentation in a suitable material that can achieve successful recovery of all fragmentation produced. Therefore, allowing the estimation of the target's response using the depth of penetration within the capture material which allows the calculation of energy absorption. The current standardized fragmentation capture material used within the UK is known as strawboard. Although effective, this material is both expensive and limited in its availability. This study explores the classification of strawboard to provide a suitable baseline to compare against medium density fibreboard (MDF) and flooring underlay, which represent two more economically friendly alternatives on the openmarket. It was found that the uniformity of response for the MDF material was better than that of strawboard, due to its reproducibility between batches and velocity ranges. To further explore this phenomena, high explosive trials were conducted, further demonstrating MDF to be a viable, reliable and cheaper alternative. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.

There is Little or No Association Between Independently Assessed Communication Strategies and Patient Ratings of Clinician Empathy.

BACKGROUND: Quality of care is increasingly assessed and incentivized using measures of patient-reported outcomes and experience. Little is known about the association between measurement of clinician communication strategies by trained observers and patient-rated clinician empathy (a patient-reported experience measure). An effective independent measure could help identify and promote clinician behaviors associated with good patient experience of care. QUESTIONS/PURPOSES: (1) What is the association between independently assessed clinician communication effectiveness and patient-rated clinician empathy? (2) Which factors are associated with independently assessed communication effectiveness? METHODS: One hundred twenty adult (age > 17 years) new or returning patients seeking musculoskeletal specialty care between September 2019 and January 2020 consented to video recording of their visit followed by completion of questionnaires rating their perceptions of providers' empathy levels in this prospective study. Patients who had operative treatment and those who had nonoperative treatment were included in our sample. We pooled new and returning patients because our prior studies of patient experience found no influence of visit type and because we were interested in the potential influences of familiarity with the clinician on empathy ratings. We did not record the number of patients or baseline data of patients who were approached, but most patients (> 80%) were willing to participate. For 7% (eight of 120 patients), there was a malfunction with the video equipment or files were misplaced, leaving 112 records available for analysis. Patients were seen by one provider among four attending physicians, four residents, or four physician assistants or nurse practitioners. The primary study question addressed the correlation between patient-rated clinician empathy using the Jefferson Scale of Patient Perceptions of Physician Empathy and clinician communication effectiveness, independently rated by two communication scholars using the Liverpool Communication Skills Assessment Scale. Based on a subset of 68 videos (61%), the interrater reliability was considered good for individual items on the Liverpool Communication Skills Assessment Scale (intraclass correlation coefficient [ICC] 0.78 [95% confidence interval (CI) 0.75 to 0.81]) and excellent for the sum of the items (that is, the total score) (ICC = 0.92 [95% CI 0.87 to 0.95]). To account for the potential association of personal factors with empathy ratings, patients completed measures of symptoms of depression (the Patient-Reported Outcome Measurement Information System depression computerized adaptive test), self-efficacy in response to pain (the two-item Pain Self-Efficacy Questionnaire), health anxiety (the five-item Short Health Anxiety Inventory), and basic demographics. RESULTS: Accounting for potentially confounding variables, including specific clinicians, marital status, and work status in the multivariable analysis, we found higher independent ratings of communication effectiveness had a slight association (odds ratio [OR] 1.1 [95% CI 1.0 to 1.3]; p = 0.02) with higher (dichotomized) ratings of patient-rated clinician empathy, while being single was associated with lower ratings (OR 0.40 [95% CI 0.16 to 0.99]; p = 0.05). Independent ratings of communication effectiveness were slightly higher for women (regression coefficient 1.1 [95% CI 0.05 to 2.2]); in addition, two of the four attending physicians were rated notably higher than the other 10 participants after controlling for confounding variables (differences up to 5.8 points on average [95% CI 2.6 to 8.9] on a 36-point scale). CONCLUSION: The observation that ratings of communication effectiveness by trained communication scholars have little or no association with patient-rated clinician empathy suggests that either effective communication is insufficient for good patient experience or that the existing measures are inadequate or inappropriate. This line of investigation might be enhanced by efforts to identify clinician behaviors associated with better patient experience, develop reliable and effective measures of clinician behaviors and patient experience, and use those measures to develop training approaches that improve patient experience. LEVEL OF EVIDENCE: Level I, prognostic study .

'I like to feel needed, you know?': a qualitative examination of sense of purpose in older care home residents.

OBJECTIVES: To explore older care home residents' experiences of maintaining a sense of purpose in life: a core component of psychological wellbeing. METHODS: Fifteen residents (9 female; 6 male), aged 60-95 years, from four care homes, were interviewed about their sense of purpose. Interview transcripts were analysed using inductive thematic analysis. RESULTS: Theme 1 ('Experiencing Loss') comprises two sub-themes that describe the impact of age-related losses on residents' sense of purpose (sub-theme 1) and the different responses that participants had to these losses (sub-theme 2). Theme 2 ('The Protective Effects of Social Connections') describes how social relationships could provide a sense of purpose, as well as the difficulties participants experienced in forming these relationships. Finally, theme 3 ('The Roles of Activities') describes the types of activities that could help residents to maintain a sense of purpose. CONCLUSION: Care home residents experience losses and barriers that make it more difficult to maintain a sense of purpose. However, with appropriate support and opportunities, residents are able to engage in activities and relationships that provide a sense of purpose. To support residents' mental health and wellbeing, care homes should offer varied opportunities for residents to engage in purposeful activities.

Assessment of non-directed computer-use behaviours in the home can indicate early cognitive impairment: A proof of principle longitudinal study.

OBJECTIVES: Computer-use behaviours can provide useful information about an individual's cognitive and functional abilities. However, little research has evaluated unaided and non-directed home computer-use. In this proof of principle study, we explored whether computer-use behaviours recorded during routine home computer-use i) could discriminate between individuals with subjective cognitive decline (SCD) and individuals with mild cognitive impairment (MCI); ii) were associated with cognitive and functional scores; and iii) changed over time. METHODS: Thirty-two participants with SCD (n = 18) or MCI (n = 14) (mean age = 72.53 years; female n = 19) participated in a longitudinal study in which their in-home computer-use behaviour was passively recorded over 7-9 months. Cognitive and functional assessments were completed at three time points: baseline; mid-point (4.5 months); and end point (month 7 to 9). RESULTS: Individuals with MCI had significantly slower keystroke speed and spent less time on the computer than individuals with SCD. More time spent on the computer was associated with better task switching abilities. Faster keystroke speed was associated with better visual attention, recall, recognition, task inhibition, and task switching. No significant change in computer-use behaviour was detected over the study period. CONCLUSION: Passive monitoring of computer-use behaviour shows potential as an indicator of cognitive abilities, and can differentiate between people with SCD and MCI. Future studies should attempt to monitor computer-use behaviours over a longer time period to capture the onset of cognitive decline, and thus could inform timely therapeutic interventions.Supplemental data for this article can be accessed online at http://dx.doi.org/10.1080/13607863.2022.2036946.