Bioenergetic mapping of 'healthy microbiomes' via compound processing potential imprinted in gut and soil metagenomes.

Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of 'healthy microbiomes' remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, our objective was to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of in silico potential for human gut and environmental soil metagenomes to process a panel of major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping 'landscape' based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of 'compound processing potential' associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60-92 % of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role of microbiota in environmental- and human-health.

Clinical, Economic, and Humanistic Outcomes Associated with Obesity Among People with Bipolar I Disorder in the United States: Analysis of National Health and Wellness Survey Data.

Introduction: People living with bipolar I disorder (BD-I) have an increased risk for obesity compared with the general population that may be related to genetic, lifestyle, and treatment factors. Few studies have examined possible effects of obesity on those living with BD-I. This study examined relationships between obesity and clinical, humanistic, and economic outcomes among adults with BD-I. Methods: This retrospective, cross-sectional study analyzed survey responses from a nationally representative sample of US adults participating in the 2016 or 2020 National Health and Wellness Survey. Respondents (18-64 years) with a self-reported physician diagnosis of BD-I were included and categorized by body mass index: underweight/normal weight (<25 kg/m2), overweight (25 to <30 kg/m2), or obese (≥30 kg/m2). Adjusted analyses assessed comorbidities, health-related quality of life (HRQoL), work productivity, health care resource utilization (HCRU), and economic outcomes. Results: In total, responses from 1,853 participants were analyzed; most were female (65%) and white (62%). Respondents with obesity had the highest prevalence of medical comorbidities, including high blood pressure (52%), sleep apnea (37%), hypercholesterolemia (34%), and type 2 diabetes (12%). Obesity was generally associated with the lowest scores of physical health and HRQoL. Activity impairment scores were highest among respondents with obesity, as were numbers of hospitalizations and emergency department visits in the previous 6 months. Respondents with obesity incurred higher annual indirect and direct medical costs ($28,178 and $37,771, respectively) when compared with the underweight/normal weight ($23,823 and $32,227, respectively) and overweight ($24,312 and $35,231, respectively) groups. Conclusion: In this nationally representative sample, obesity was associated with several outcomes that may negatively affect people living with BD-I, including medical comorbidities, higher HCRU, HRQoL impairments, and greater indirect and direct medical costs. These findings highlight the importance of considering the presence of or risk for obesity and associated medical comorbidities when treating BD-I.

Emergent community architecture despite distinct diversity in the global whale shark (Rhincodon typus) epidermal microbiome.

Microbiomes confer beneficial physiological traits to their host, but microbial diversity is inherently variable, challenging the relationship between microbes and their contribution to host health. Here, we compare the diversity and architectural complexity of the epidermal microbiome from 74 individual whale sharks (Rhincodon typus) across five aggregations globally to determine if network properties may be more indicative of the microbiome-host relationship. On the premise that microbes are expected to exhibit biogeographic patterns globally and that distantly related microbial groups can perform similar functions, we hypothesized that microbiome co-occurrence patterns would occur independently of diversity trends and that keystone microbes would vary across locations. We found that whale shark aggregation was the most important factor in discriminating taxonomic diversity patterns. Further, microbiome network architecture was similar across all aggregations, with degree distributions matching Erdos-Renyi-type networks. The microbiome-derived networks, however, display modularity indicating a definitive microbiome structure on the epidermis of whale sharks. In addition, whale sharks hosted 35 high-quality metagenome assembled genomes (MAGs) of which 25 were present from all sample locations, termed the abundant 'core'. Two main MAG groups formed, defined here as Ecogroup 1 and 2, based on the number of genes present in metabolic pathways, suggesting there are at least two important metabolic niches within the whale shark microbiome. Therefore, while variability in microbiome diversity is high, network structure and core taxa are inherent characteristics of the epidermal microbiome in whale sharks. We suggest the host-microbiome and microbe-microbe interactions that drive the self-assembly of the microbiome help support a functionally redundant abundant core and that network characteristics should be considered when linking microbiomes with host health.

Burden of chronic cough in the UK: results from the 2018 National Health and Wellness Survey.

Background: Chronic cough, defined as daily cough for at least 8 weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the UK. Methods: Study participants were general population respondents to the 2018 UK National Health and Wellness Survey (NHWS). Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matchingon age, sex and the modified Charlson Comorbidity Index. Results: Of 15 000 NHWS respondents, 715 reported chronic cough in the previous 12 months and 918 during their lifetime. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence was 6.2%. Prevalence of chronic cough was higher among older respondents and those with smoking histories. Chronic cough respondents experienced higher rates of severe anxiety and depression in the past 2 weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents visited a healthcare provider in the past 6 months than respondents without chronic cough with a mean of 5.8 and 3.7 visits per respondent, respectively. Conclusion: Adults with chronic cough report lower quality of life, reduced work productivity and greater healthcare resource utilisation than matched controls without chronic cough.

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups.

BACKGROUND: Schizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I. METHODS: Six 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable. RESULTS: Among participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem. CONCLUSIONS: People living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients' experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

Defining marine bacterioplankton community assembly rules by contrasting the importance of environmental determinants and biotic interactions.

Bacterioplankton communities govern marine productivity and biogeochemical cycling, yet drivers of bacterioplankton assembly remain unclear. Here, we contrast the relative contribution of deterministic processes (environmental factors and biotic interactions) in driving temporal dynamics of bacterioplankton diversity at three different oceanographic time series locations, spanning 15° of latitude, which are each characterized by different environmental conditions and varying degrees of seasonality. Monthly surface samples (5.5 years) were analysed using 16S rRNA amplicon sequencing. The high- and mid-latitude sites of Maria Island and Port Hacking were characterized by high and intermediate levels of environmental heterogeneity, respectively, with both alpha diversity (72%; 24% of total variation) and beta diversity (32%; 30%) patterns within bacterioplankton assemblages explained by day length, ammonium, and mixed layer depth. In contrast, North Stradbroke Island, a sub-tropical location where environmental conditions are less variable, interspecific interactions were of increased importance in structuring bacterioplankton diversity (alpha: 33%; beta: 26%) with environment only contributing 11% and 13% to predicting diversity, respectively. Our results demonstrate that bacterioplankton diversity is the result of both deterministic environmental and biotic processes and that the importance of these different deterministic processes varies, potential in response to environmental heterogeneity.

The Epidermal Microbiome Within an Aggregation of Leopard Sharks (Triakis semifasciata) Has Taxonomic Flexibility with Gene Functional Stability Across Three Time-points.

The epidermis of Chondrichthyan fishes consists of dermal denticles with production of minimal but protein-rich mucus that collectively, influence the attachment and biofilm development of microbes, facilitating a unique epidermal microbiome. Here, we use metagenomics to provide the taxonomic and functional characterization of the epidermal microbiome of the Triakis semifasciata (leopard shark) at three time-points collected across 4 years to identify links between microbial groups and host metabolism. Our aims include (1) describing the variation of microbiome taxa over time and identifying recurrent microbiome members (present across all time-points); (2) investigating the relationship between the recurrent and flexible taxa (those which are not found consistently across time-points); (3) describing the functional compositions of the microbiome which may suggest links with the host metabolism; and (4) identifying whether metabolic processes are shared across microbial genera or are unique to specific taxa. Microbial members of the microbiome showed high similarity between all individuals (Bray-Curtis similarity index = 82.7, where 0 = no overlap, 100 = total overlap) with the relative abundance of those members varying across sampling time-points, suggesting flexibility of taxa in the microbiome. One hundred and eighty-eight genera were identified as recurrent, including Pseudomonas, Erythrobacter, Alcanivorax, Marinobacter, and Sphingopxis being consistently abundant across time-points, while Limnobacter and Xyella exhibited switching patterns with high relative abundance in 2013, Sphingobium and Sphingomona in 2015, and Altermonas, Leeuwenhoekiella, Gramella, and Maribacter in 2017. Of the 188 genera identified as recurrent, the top 19 relatively abundant genera formed three recurrent groups. The microbiome also displayed high functional similarity between individuals (Bray-Curtis similarity index = 97.6) with gene function composition remaining consistent across all time-points. These results show that while the presence of microbial genera exhibits consistency across time-points, their abundances do fluctuate. Microbial functions however remain stable across time-points; thus, we suggest the leopard shark microbiomes exhibit functional redundancy. We show coexistence of microbes hosted in elasmobranch microbiomes that encode genes involved in utilizing nitrogen, but not fixing nitrogen, degrading urea, and resistant to heavy metal.

Epidermal Microbiomes of Leopard Sharks (Triakis semifasciata) Are Consistent across Captive and Wild Environments.

Characterizations of shark-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California born and held permanently in captivity), semi-captive (held in captivity for <1 year in duration and scheduled for release; Scripps Institute of Oceanography, San Diego, CA, USA) and wild environments (Moss Landing and La Jolla, CA, USA). Here, we report captive environments do not drive epidermal microbiome compositions of T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as Metagenomes associated genomes revealed a consistent relationship across captive, semi-captive, and wild populations. Since changes in microbial communities is often associated with poor health outcomes, our report illustrates that epidermally associated microbes belonging to T. semifasciata are not suffering detrimental impacts from long or short-term captivity. Therefore, conservation programs which house sharks in aquariums are providing a healthy environment for the organisms on display. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel associations that are consistent across captive gradients.

Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States.

BACKGROUND: Schizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25-1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed. OBJECTIVE: We conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA. DATA SOURCES: We searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars. STUDY ELIGIBILITY: Observational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included. RESULTS: Eighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine. LIMITATIONS: This systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system. CONCLUSIONS: In the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.

Schizophrenia is a debilitating mental disorder that affects up to 1.6% of adults in the USA. Antipsychotic medications reduce symptoms of the disease, but many patients with schizophrenia are not fully adherent or choose to discontinue treatment entirely, increasing their risk of hospitalization. In others, efforts to achieve better symptom control or to avoid intolerable side effects may result in switching antipsychotic medications or adding additional medications, leading to higher medical treatment costs. The magnitude of these cost increases is unclear. This study sought to assess medical costs associated with antipsychotic treatment adherence, switching, and adding additional antipsychotics. We reviewed 81 studies published from January 2008 through June 2018 examining treatment adherence in patients with schizophrenia. We calculated rates of adherence, switching, and adding antipsychotics, as well as associated medical costs. Overall adherence to antipsychotic treatment was less than 50%, with up to 50% of patients switching medications and up to 29% adding an additional antipsychotic medication to their current treatment. Patients who were not treatment adherent incurred annual medical costs of $10,316 compared with $5723 in patients who were adherent. The costs of immediate or delayed switching of antipsychotic medications ranged from $21,922 to $28,232, while costs of adding an additional antipsychotic ranged from $24,045 to $29,344. These data suggest that suboptimal medication adherence, along with high rates of patient discontinuation and medication switching, lead to higher treatment costs in the management of patients with schizophrenia.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.

BACKGROUND: Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS: Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS: Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS: In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

Burden of chronic low back pain: Association with pain severity and prescription medication use in five large European countries.

OBJECTIVE: This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health-related quality of life, health status, work productivity, and healthcare resource utilization. METHODS: This cross-sectional study utilized SF-12, EQ-5D-5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self-reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx-treated or Rx-untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. RESULTS: Of 2086 respondents with CLBP, 683 had mild pain (276 Rx-untreated, 407 Rx-treated) and 1403 had moderate/severe pain (781 Rx-untreated, 622 Rx-treated). Respondents with moderate/severe pain had significantly worse health-related quality of life (SF-12v2 physical component summary), health status (EQ-5D-5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx-untreated (moderate/severe pain Rx-untreated vs. mild pain Rx-untreated, p ≤ 0.05) and Rx-treated (moderate/severe pain Rx-treated vs. mild pain Rx-treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx-treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx-untreated (8.72 vs. 7.61, p = 0.072) groups. Health-related quality of life (SF-12v2 physical component summary) and health status (EQ-5D-5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx-treated group compared with all other groups (all p ≤ 0.05). CONCLUSION: Greater severity of CLBP was associated with worse health-related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users.

Elasmobranch microbiomes: emerging patterns and implications for host health and ecology.

Elasmobranchs (sharks, skates and rays) are of broad ecological, economic, and societal value. These globally important fishes are experiencing sharp population declines as a result of human activity in the oceans. Research to understand elasmobranch ecology and conservation is critical and has now begun to explore the role of body-associated microbiomes in shaping elasmobranch health. Here, we review the burgeoning efforts to understand elasmobranch microbiomes, highlighting microbiome variation among gastrointestinal, oral, skin, and blood-associated niches. We identify major bacterial lineages in the microbiome, challenges to the field, key unanswered questions, and avenues for future work. We argue for prioritizing research to determine how microbiomes interact mechanistically with the unique physiology of elasmobranchs, potentially identifying roles in host immunity, disease, nutrition, and waste processing. Understanding elasmobranch-microbiome interactions is critical for predicting how sharks and rays respond to a changing ocean and for managing healthy populations in managed care.

Prevalence and Burden of Chronic Cough in the United States.

BACKGROUND: Chronic cough is a common complaint but there are little population-based data on its burden in the United States. OBJECTIVE: To determine the prevalence of chronic cough and its burden on individuals and the health care system. METHODS: This was a survey of respondents who completed the 2018 National Health and Wellness Survey and questions about sleep and health care resource use. Chronic cough was defined as having a daily cough for 8 or more weeks. Respondents without chronic cough were selected through propensity score matching. Chronic cough prevalence was estimated using poststratification sampling weights calculated using U.S. Census data and post-data Horvitz-Thompson sampling weights to adjust for sampling bias. RESULTS: Of 74,977 National Health and Wellness Survey respondents, 3,654 had experienced chronic cough in the previous 12 months, for a weighted prevalence of 5.0%. Respondents with chronic cough were older and more predominantly female than respondents without chronic cough (both P < .001). Compared with matched respondents without chronic cough, those with chronic cough had lower mean scores on the Medical Outcomes Study 36-item Short Form Survey v2 physical (P < .001) and mental (P < .001) component summary scores. More respondents with chronic cough than matched controls experienced severe anxiety and severe depression in the past 2 weeks, work productivity impairment, impaired sleep quality and daytime sleepiness, as well as more emergency department visits and hospitalizations in the past 6 months (P < .001 for all comparisons). CONCLUSIONS: The burden of chronic cough manifests itself as reduced health-related quality of life, increased anxiety and depression, impaired sleep and work productivity, and greater health care utilization.

Disconnect in Assessments of Autosomal Dominant Polycystic Kidney Disease Burden Between Patients and Physicians: A Survey Study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare inherited kidney disorder with considerable symptom burden and negative effects even in early-stage disease. Patients' reporting of ADPKD symptom burden may differ from physicians' impressions. In this quantitative, cross-section survey study, we evaluated patient and physician assessments of symptom burden at early- and late-stage ADPKD. METHODS: In the United States, 300 patients with ADPKD and 155 physicians treating patients with ADPKD completed online surveys administered by Kantar. Disease stage was categorized as early (chronic kidney disease [CKD] stages 1-3) or late (stages 4-5). Patients completed the Work Productivity and Activity Impairment Questionnaire and reported current disease symptoms. Patients and physicians assessed impacts of ADPKD on daily life and burden of specific symptoms. Statistical analyses compared patient versus physician responses stratified by early- versus late-stage ADPKD. RESULTS: We found that impairment in work productivity was statistically greater in late- versus early-stage CKD. Compared with physicians' impressions, patients were more likely at early stages and less likely at later stages to report a moderate/strong impact of ADPKD on daily life. Among patients, 74% with early- and 88% with late-stage disease reported that ADPKD caused them to modify their daily lives. In early-stage disease, patients reported a statistically greater burden from feeling exhausted and less burden from dull kidney pain, cardiovascular problems, high blood pressure, and liver cysts than physicians assumed. At later stages, patients reported feeling exhausted and skeletal/joint pain as more burdensome, and frequent urination, high blood pressure, liver cysts, and hematuria as less burdensome, compared with physicians' impressions. CONCLUSION: The results of this survey study demonstrate a disconnect between patients' experiences and physicians' awareness of the burden of ADPKD and highlight the need for more patient/physician discussion of symptoms and disease management.

Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

OBJECTIVE: Treatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns. METHODS: Structured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008-2018) describing real-world SGA use in adults with bipolar disorder/BD-I. RESULTS: Among 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs. LIMITATIONS: Different definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived. CONCLUSION: Despite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.

Exploring the taxonomical and functional profile of As Burgas hot spring focusing on thermostable ß-galactosidases.

In the present study we investigate the microbial community inhabiting As Burgas geothermal spring, located in Ourense (Galicia, Spain). The approximately 23 Gbp of Illumina sequences generated for each replicate revealed a complex microbial community dominated by Bacteria in which Proteobacteria and Aquificae were the two prevalent phyla. An association between the two most prevalent genera, Thermus and Hydrogenobacter, was suggested by the relationship of their metabolism. The high relative abundance of sequences involved in the Calvin-Benson cycle and the reductive TCA cycle unveils the dominance of an autotrophic population. Important pathways from the nitrogen and sulfur cycle are potentially taking place in As Burgas hot spring. In the assembled reads, two complete ORFs matching GH2 beta-galactosidases were found. To assess their functional characterization, the two ORFs were cloned and overexpressed in E. coli. The pTsbg enzyme had activity towards o-Nitrophenyl-ß-D-galactopyranoside (ONPG) and p-Nitrophenyl-ß-D-fucopyranoside, with high thermal stability and showing maximal activity at 85 °C and pH 6, nevertheless the enzyme failed to hydrolyze lactose. The other enzyme, Tsbg, was unable to hydrolyze even ONPG or lactose. This finding highlights the challenge of finding novel active enzymes based only on their sequence.

Are pain severity and current pharmacotherapies associated with quality of life, work productivity, and healthcare utilisation for people with osteoarthritis in five large European countries?

OBJECTIVES: Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status. METHODS: This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status. RESULTS: Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p<0.01). HRU such as the mean number of emergency room visits for >6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p<0.05). CONCLUSIONS: Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.

Antipsychotic Treatment Experiences of People with Schizophrenia: Patient Perspectives from an Online Survey.

BACKGROUND: This survey examined the experiences of people living with schizophrenia who have used oral antipsychotics (APs). METHODS: Adults with self-reported physician-diagnosed schizophrenia (N=200), who were members of an online research participation panel and reported taking one or more oral APs within the last year, completed a cross-sectional online survey that focused on direct report of their experiences regarding APs (eg, symptoms, side effects, adherence). Descriptive analyses were conducted for the total survey sample and for subgroups defined a priori by experience with specific, prevalent side effects. RESULTS: The mean age of the sample was 41.9 (SD=11.0) years, 50% of participants were female, and 32% were nonwhite. Overall ratings were positive for medication effectiveness and convenience but negative for side effects. While most participants reported that APs improved schizophrenia symptoms (92%), 27% reported APs as having done "more harm than good." Almost all participants (98%) reported experiencing side effects of APs, with the most common being anxiety (88%), feeling drowsy/tired (86%), and trouble concentrating (85%). Side effects frequently cited as either "extremely" or "very" bothersome were weight gain (56%), sexual dysfunction (55%), and trouble concentrating (54%). Over 80% reported that side effects had negatively impacted their work and social functioning (eg, social activities or family/romantic relationships). Since initiating treatment, 56% of respondents had stopped taking APs at some point (65% of these due to side effects). Side effects commonly reported as having led to stopping AP treatment were "feeling like a 'zombie'" (22%), feeling drowsy/tired (21%), and weight gain (20%). CONCLUSION: Most participants reported improvements in schizophrenia symptoms associated with the use of APs. However, most participants also reported experiencing numerous bothersome side effects that negatively impacted their work, social functioning, and treatment adherence. Results highlight the unmet need for new APs with favorable benefit-risk profiles.