Nursing Home Characteristics Associated with Antipsychotic Prescribing After Implementation of the National Antipsychotic Reduction Initiative (ARI).

OBJECTIVES: To describe nursing home (NH) characteristics associated with antipsychotic use and test whether associations changed after implementation of the National Partnership to Improve Dementia Care's antipsychotic reduction initiative (ARI). METHODS: Longitudinal quasi-experimental design using data from multiple sources and piecewise linear mixed models were used for statistical analyses. RESULTS: There was a significant decrease in monthly antipsychotic use across the study period (pre-ARI b = -0.0003, p <.001; post-ARI b = -0.0012, p <.001), which held after adjusting for NH characteristics. Registered nurse hours (b = -0.0026, p <.001), licensed practical nurse hours (b = -0.0019, p <.001), facility chain membership (b = -0.0013, p <.01), and health inspection ratings (b = -0.0003, p >.01) were associated with decreased antipsychotic use. Post-ARI changes in associations between NH characteristics and antipsychotic use were small and not statistically significant. CONCLUSIONS: Decreases in antipsychotic use were associated with most NH characteristics, and associations persisted post-ARI. Further research is warranted to examine the interactions between ARI policy and NH characteristics on antipsychotic prescribing, as well as other NH factors, such as facility prescribing cultures and clinical specialty of staff. CLINICAL IMPLICATIONS: Decreases in monthly antipsychotic use were observed following the ARI. The decreases in monthly antipsychotic use were associated with most NH characteristics, and these associations persisted during the post-ARI period.

Knowledge-building in an environment mediated by digital technology: A case study in higher education.

The advancement of technology in recent years seems to be prompting a re-ontologising of the world. Digital technology is transforming the educational spaces we inhabit, as well as our way of processing information. Although there are already numerous studies that have addressed this technological reality, only a handful have done so from a theoretical perspective. That is why we present research that seeks to reinforce the latest theoretical contributions for understanding how modern technology may be affecting the way in which knowledge is built. Based on the latest research in social constructivism, this is a qualitative study designed to contribute to the creation of a specific theoretical framework for an onlife world. An ill-structured task and a semi-structured interview were used to observe the use of the thinking skills that enable us to build knowledge and the relationship between them. The results show that the ways of building knowledge are changing, as digital technology fosters the use of higher-order thinking skills that, furthermore, operate in a chaotic, complex, and unpredictable manner. In conclusion, this study upholds the notion that the ways of building knowledge are changing, but we still need more empirical contributions to create a generally accepted theoretical construct for explaining how we build knowledge through digital technology.

HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.

Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments.IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the functional properties of HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1-specific IgA, specifically for vaccine-elicited IgA. Characterization of the functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human vaccine clinical trials are critical toward understanding the capacity of the host immune response to block HIV-1 acquisition.

Algorithm for Identifying Nursing Home Days Using Medicare Claims and Minimum Data Set Assessment Data.

BACKGROUND: No consensus exists about methods of measuring nursing home (NH) length-of-stay for Medicare beneficiaries to identify long-stay and short-stay NH residents. OBJECTIVES: To develop an algorithm measuring NH days of stay to differentiate between residents with long and short stay (≥101 and <101 consecutive days, respectively) and to compare the algorithm with Minimum Data Set (MDS) alone and Medicare claims data. RESEARCH DESIGN: We linked 2006-2009 MDS assessments to Medicare Part A skilled nursing facility (SNF) data. This algorithm determined the daily NH stay evidence by MDS and SNF dates. NH length-of-stay and characteristics were reported in the total, long-stay, and short-stay residents. Long-stay residents identified by the algorithm were compared with the NH evidence from MDS-alone and Medicare parts A and B data. RESULTS: Of 276,844 residents identified by our algorithm, 40.8% were long stay. Long-stay versus short-stay residents tended to be older, male, white, unmarried, low-income subsidy recipients, have multiple comorbidities, and have higher mortality but have fewer hospitalizations and SNF services. Higher proportions of long-stay and short-stay residents identified by the MDS/SNF algorithm were classified in the same group using MDS-only (98.9% and 100%, respectively), compared with the parts A and B data (95.0% and 67.1%, respectively). NH length-of-stay was similar between MDS/SNF and MDS-only long-stay residents (mean±SD: 717±422 vs. 720±441 d), but the lengths were longer compared with the parts A and B data (approximately 474±393 d). CONCLUSIONS: Our MDS/SNF algorithm allows the differentiation of long-stay and short-stay residents, resulting in an NH group more precise than using Medicare claims data only.

Antipsychotic medication use in nursing homes: a proposed measure of quality.

OBJECTIVE: The potential misuse of antipsychotic medications (APMs) is an ongoing quality concern in nursing homes (NHs), especially given recent black box warnings and other evidence regarding the risk of APMs when used in NH populations. One mechanism regulators could use is public reporting of APM use by NHs; however, there is currently no agreed-upon measure of guideline-inconsistent APM use. In this paper, we describe a proposed measure of quality of APM use that is based on Centers for Medicare and Medicaid Services (CMS) Interpretive Guidelines, Food and Drug Administration (FDA) indications for APMs, and severity of behavioral symptoms. METHODS: The proposed measure identifies NH residents who receive an APM but do not have an approved indication for APM use. We demonstrate the feasibility of this measure using data from Medicaid-eligible long-stay residents aged 65 years and older in seven states. Using multivariable logistic regressions, we compare it to the current CMS Nursing Home Compare quality measure. RESULTS: We find that nearly 52% of residents receiving an APM lack indications approved by CMS/FDA guidelines compared with 85% for the current CMS quality measure. APM guideline-inconsistent use rates vary significantly across resident and facility characteristics, and states. Only our measure correlates with another quality indicator in that facilities with higher deficiencies have significantly higher odds of APM use. Predictors of inappropriate use are found to be consistent with other measures of NH quality, supporting the validity of our proposed measure. CONCLUSION: The proposed measure provides an important foundation to improve APM prescribing practices without penalizing NHs when there are limited alternative treatments available.

Acute Visual Disturbances and Ataxia Secondary to Attempted COVID-19 Prophylaxis With Ivermectin in a Nine-Year-Old.

Ivermectin is an antiparasitic agent listed as an essential medication by the World Health Organization. Ivermectin utilization has increased due to the popular, though inaccurate, perception of its use in COVID-19 management. Poison Control Central calls regarding ivermectin toxicity have increased 245% since pre-pandemic baselines. This case study illustrates the clinical presentation of ivermectin toxicity in a nine-year-old child with acute vision changes and ataxia. The child was given 60 mg (1 mg/kg) of veterinary-grade ivermectin by a parent, 10 times the clinically recommended dose of 0.1 mg/kg, as prophylaxis after household exposure to COVID-19. Ten hours later, the child developed new-onset blurry vision, a perception of red dots in the peripheral vision, dizziness, and balance issues. Physical examination was notable for pulsating pupils, ataxia, and dysmetria. Symptoms resolved completely after 10 hours. Ivermectin ingestion is an important diagnostic consideration in children presenting with similar symptoms. We hope our case aids in the identification of ivermectin toxicity and hastens necessary supportive measures.

Unintended impacts of a national antipsychotic reduction initiative among nursing facility residents with and without Alzheimer's disease.

BACKGROUND: In July 2012, the Centers for Medicare & Medicaid services launched an antipsychotic reduction initiative (ARI) to improve care for nursing facility residents with Alzheimer's disease and related dementias (ADRD). We examined the impact of this policy on antipsychotic and psychotropic medication (PM) utilization and diagnosis patterns in long-stay nursing facility residents with ADRD and other conditions in which antipsychotics are indicated. METHODS: Using an 80% sample of fee-for-service Medicare beneficiaries with Part D, we conducted a retrospective cohort study of nursing facility residents with ADRD, bipolar disorder, psychosis, Parkinson's disease, and residents exempt from the policy due to diagnoses of schizophrenia, Tourette syndrome, and/or Huntington's disease. We used interrupted time-series analyses to compare changes in diagnoses, antipsychotic use, and PM utilization before (January 1, 2011-June 30, 2012) and after (July 1, 2012-September 30, 2015) ARI implementation. RESULTS: We identified 874,487 long-stay nursing facility residents with a diagnosis of ADRD (n = 358,518), exempt (n = 92,859), bipolar (n = 128,298), psychosis (n = 93,402), and Parkinson's disease (n = 80,211). In all cohorts, antipsychotic use declined prior to the ARI; upon policy implementation, antipsychotic use reductions were sustained throughout the study period, including statistically significant ARI-associated accelerated declines in all cohorts. PM changes varied by cohort, with ARI-associated increases in non-benzodiazepine sedatives and/or muscle relaxants noted in ADRD, psychosis, and Parkinson's cohorts. Although anticonvulsant use increased throughout the study period in all groups, with the exception of the bipolar cohort, these increases were not associated with ARI implementation. Findings are minimally explained by increased post-ARI membership in the psychosis and Parkinson's cohorts. CONCLUSIONS: Our study documents antipsychotic use significantly declined in non-ADRD clinical and exempt cohorts, where such reductions may not be clinically warranted. Furthermore, ARI-associated compensatory increases in PMs do not offset these reductions. Changes in PM utilization and diagnostic make-up of residents using PMs require further investigation to assess the potential for adverse clinical and economic outcomes.

Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation.

Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 broadly neutralizing antibody (bNAb) uses the V(H)2-5 gene, which has 10 distinct alleles that use either a heavy-chain complementarity-determining region 2 (HCDR2) aspartic acid (D(H54)) or an HCDR2 asparagine (N(H54)) residue. The 2F5 HCDR2 D(H54) residue has been shown to form a salt bridge with gp41 (665)K; the V(H)2-5 germ line allele variant containing N(H54) cannot do so and thus should bind less avidly to gp41. Thus, the induction of 2F5 bNAb is dependent on both genetic and structural factors that could affect antigen affinity of unmutated naïve B cell receptors. Here, we studied allelic variants of the V(H)2-5 inferred germ line forms of the HIV-1 gp41 bNAb 2F5 for their antigen binding affinities to gp41 linear peptide and conformational protein antigens. Both V(H)2-5 2F5 inferred germ line variants bound to gp41 peptides and protein, including the fusion intermediate protein mimic, although more weakly than the mature 2F5 antibody. As predicted, the affinity of the N(H54) variant for fusion-intermediate conformation was an order of magnitude lower than that of the D(H54) V(H)2-5 germ line antibody, demonstrating that allelic variants of 2F5 germ line antibodies differentially bind to gp41. Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design.

Response to regulatory stringency: the case of antipsychotic medication use in nursing homes.

This paper studies the impact of regulatory stringency, as measured by the statewide deficiency citation rate over the past year, on the quality of care provided in a national sample of nursing homes from 2000 to 2005. The quality measure used is the proportion of residents who are using antipsychotic medication. Although the changing case-mix of nursing home residents accounts for some of the increase in the use of antipsychotics, we find that the use of antipsychotics by nursing homes is responsive to state regulatory enforcement in a manner consistent with the multitasking incentive problem. Specifically, the effect of the regulations is dependent on the degree of complementarity between the regulatory deficiency and the use of antipsychotics.

Talon Noir in a Young Baseball Player: A Case Report.

When evaluating pediatric patients with hyperpigmented lesions on the plantar aspect of the feet, the differential diagnosis should include talon noir, acral melanoma, and verruca with thrombosis. Talon noir are asymptomatic brown-black pigmented macules formed by intraepidermal hemorrhages of the feet caused by shear-force injury. Spontaneous resolution of talon noir typically occurs within 2-3 weeks. Clinicians should ensure that their patients who participate in sports have appropriately fitting shoes, which may prevent these lesions from occurring. This case report highlights a unique case of talon noir occurring in a young baseball player with an atypical distribution of plantar macules.

Assessing medication exposures and outcomes in the frail elderly: assessing research challenges in nursing home pharmacotherapy.

BACKGROUND: Large administrative datasets such as Medicare and Medicaid claims have much potential utility in clinical and comparative effectiveness (CE) studies. Among their advantages are the inclusion of clinically heterogeneous populations, without exclusions typical in clinical trials; the ability to study extremely large study populations with power to examine differential outcomes across individual drugs, treatment effect modification, and the risk of uncommon outcomes. However, claims data by themselves are subject to many limitations, notably, in their lack of information on such clinical characteristics as functional status, behaviors, and symptoms, which are important both as outcomes and as covariates. METHODS: We describe data from multiple sources including standardized, electronically recorded clinical and functional data from the Nursing Home (NH) Minimum Data Set; prescription drug data from Medicaid and Medicare claims; and facility data. We present the strengths and challenges of using merged data about the NH population to study prescription drug exposures and outcomes in the frail elderly, and suggest strategies to address methodological difficulties. RESULTS: Merged data from NH sources can support unique study designs in CE research and provide great power. However, given the differing longitudinal structure, timing of observations, and other complex features of the underlying data sources, such studies pose many challenging design and analytic issues. CONCLUSIONS: Integrated data on the NH population have great potential for CE research among frail elderly persons, if methodological and measurement challenges can be adequately addressed.

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.

Determinants of remaining in the community after discharge: results from New Jersey's Nursing Home Transition Program.

PURPOSE: To inform states with nursing home transition programs, we determine what risk factors are associated with participants' long-term readmission to nursing homes within 1 year after discharge. DESIGN AND METHODS: We obtained administrative data for all 1,354 nursing home residents who were discharged, and we interviewed 628 transitioning through New Jersey's nursing home transition program in 2000. We used the Andersen behavioral model to select predictors of long-term nursing home readmission, and we used Cox proportional hazards regressions to examine the relative risk of experiencing such readmissions. RESULTS: Overall, 72.6% of the 1,354 individuals remained in the community, with 8.6% readmitted to a nursing home for long stays (>90 days) and 18.8% dying during the study year. Cox proportional hazards regression analysis showed that being male, single, and dissatisfied with one's living situation; living with others; and falling within 8 to 10 weeks after discharge were significant predictors of long-term nursing home readmission during the first year after discharge. IMPLICATIONS: Most of the factors predicting long-term readmission were predisposing, not need, factors. This fact points to the limits of formulaic approaches to assessing candidates for discharge and the importance of working with clients to understand and address their particular vulnerabilities. Consumers, state policy makers, nursing home transition staff, discharge planners, and caregivers can use these findings to understand and help clients understand their particular risks and options, and to identify those individuals needing the greatest attention during the transition period as well as risk-specific services such as fall-prevention programs that should be made available to them.

CMS Strategies To Reduce Antipsychotic Drug Use In Nursing Home Patients With Dementia Show Some Progress.

The Centers for Medicare and Medicaid Services initiated three strategies (in March and July 2012 and in May 2013) to reduce the use of unnecessary antipsychotic medications in nursing homes, especially their widespread use to control behavioral symptoms of dementia. We examined 86,163 state recertification surveys conducted at 15,055 facilities in the period January 1, 2009-March 31, 2015. We found that these strategies were associated with increases in citations for only one of two targeted deficiencies (unnecessary drug use) and only after the third strategy (revisions to the federal guidelines for the citations) was implemented. Each strategy was associated with a modest but significant reduction in antipsychotic prevalence in the general nursing home population. Initial reductions were greater in the ten states with the highest prevalence of antipsychotic use in nursing homes, compared to the ten states with the lowest prevalence. Use of other psychoactive medications, some of which are potential substitutes for antipsychotics, varied with each strategy and by state. Continuous monitoring and consistent enforcement are needed to ensure the continued decline in unnecessary use of antipsychotics and psychoactive medications in nursing homes.

Fall and Fracture Risk in Nursing Home Residents With Moderate-to-Severe Behavioral Symptoms of Alzheimer's Disease and Related Dementias Initiating Antidepressants or Antipsychotics.

BACKGROUND: Both antidepressants and antipsychotics are used in older adults with behavioral symptoms of Alzheimer's disease and related dementias. Despite the prevalent use of these agents, little is known about their comparative risks for falls and fractures. METHODS: Using 2007-2009 Medicare claims data linked to Minimum Data Set 2.0, we identified new users of antidepressants and antipsychotics among nursing home residents with Alzheimer's disease and related dementias who had moderate-to-severe behavioral symptoms. Separate discrete-time survival models were used to estimate risks of falls, fractures, and a composite of both among antidepressant group versus antipsychotic group. RESULTS: Compared to antipsychotic users, antidepressant users experienced significantly higher risk for fractures (adjusted hazard ratio = 1.35, 95% confidence interval = 1.10-1.66). The overall risk of falls or fractures remained significant in the antidepressant versus antipsychotic group (adjusted hazard ratio = 1.16, 95% confidence interval = 1.02-1.32). CONCLUSIONS: Antidepressants are associated with higher fall and fracture risk compared to antipsychotics in the management of older adults with Alzheimer's disease and related dementias who experience moderate-to-severe behavioral symptoms. Clinicians need to assess the ongoing risks/benefits of antidepressants for these symptoms especially in light of the increasingly prevalent use of these agents.

Creating needs-based tiered models for assisted living reimbursement.

PURPOSE: This research provides state policy makers and others interested in developing needs-based reimbursement models for Medicaid-funded assisted living with an evaluation of different methodologies that affect the structure and outcomes of these models. DESIGN AND METHODS: We used assessment data from Medicaid-enrolled assisted living residents and waiver-eligible community-dwelling individuals (N = 726) in order to evaluate five methodologies in the design of these tiered needs-based models. We used ordinary least squares regression analyses in order to evaluate each model's ability to predict the time needed to care for individuals with varying needs (e.g., activities of daily living limitations, dementia, special services.) RESULTS: These models varied in fit from .127 to a high of .357 using the adjusted R2 statistic. Both count and weighted models adequately predicted service needs and discriminated individuals into their appropriate tiers well. Weighted models with the largest score range worked best and provided more flexibility. IMPLICATIONS: Policy makers can tailor the generic tiered models developed with these methods to a state's population. Any state considering adoption of a needs-based tiered model will need to refine its model based on its assisted living population characteristics, its resources, and how the model fits its long-term care system. For the industry, these models can serve to identify levels of care needed in planning for staff time and skill mix required for assisted living as well as other long-term care populations.

Short-Term Dynamics of North Sea Bacterioplankton-Dissolved Organic Matter Coherence on Molecular Level.

Remineralization and transformation of dissolved organic matter (DOM) by marine microbes shape the DOM composition and thus, have large impact on global carbon and nutrient cycling. However, information on bacterioplankton-DOM interactions on a molecular level is limited. We examined the variation of bacterial community composition (BCC) at Helgoland Roads (North Sea) in relation to variation of molecular DOM composition and various environmental parameters on short-time scales. Surface water samples were taken daily over a period of 20 days. Bacterial community and molecular DOM composition were assessed via 16S rRNA gene tag sequencing and ultrahigh resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), respectively. Environmental conditions were driven by a coastal water influx during the first half of the sampling period and the onset of a summer phytoplankton bloom toward the end of the sampling period. These phenomena led to a distinct grouping of bacterial communities and DOM composition which was particularly influenced by total dissolved nitrogen (TDN) concentration, temperature, and salinity, as revealed by distance-based linear regression analyses. Bacterioplankton-DOM interaction was demonstrated in strong correlations between specific bacterial taxa and particular DOM molecules, thus, suggesting potential specialization on particular substrates. We propose that a combination of high resolution techniques, as used in this study, may provide substantial information on substrate generalists and specialists and thus, contribute to prediction of BCC variation.

Distinct compositions of free-living, particle-associated and benthic communities of the Roseobacter group in the North Sea.

The Roseobacter group is one of the predominant lineages in the marine environment. While most investigations focus on pelagic roseobacters, the distribution and metabolic potential of benthic representatives is less understood. In this study, the diversity of the Roseobacter group was characterized in sediment and water samples along the German/Scandinavian North Sea coast by 16S rRNA gene analysis and cultivation-based methods. Molecular analysis indicated an increasing diversity between communities of the Roseobacter group from the sea surface to the seafloor and revealed distinct compositions of free-living and attached fractions. Culture media containing dimethyl sulfide (DMS), dimethyl sulfonium propionate (DMSP) or dimethyl sulfoxide (DMSO) stimulated growth of roseobacters showing highest most probable numbers (MPN) in DMSO-containing dilutions of surface sediments (2.1 × 10(7) roseobacters cm(-3)). Twenty roseobacters (12 from sediments) were isolated from DMSP- and DMS-containing cultures. Sequences of the isolates represented 0.04% of all Bacteria and 4.7% of all roseobacters in the pyrosequencing dataset from sediments. Growth experiments with the isolate Shimia sp. SK013 indicated that benthic roseobacters are able to switch between aerobic and anaerobic utilization of organic sulfur compounds. This response to changing redox conditions might be an adaptation to specific environmental conditions on particles and in sediments.

Mortality Risk of Antipsychotic Dose and Duration in Nursing Home Residents with Chronic or Acute Indications.

OBJECTIVES: To examine disease-specific associations between antipsychotic dose and duration and all-cause mortality. DESIGN: Retrospective cohort study. SETTING: A 5% random sample of Medicare beneficiaries who had a Minimum Data Set 2.0 clinical assessment completed between 2007 and 2009. PARTICIPANTS: Three mutually exclusive cohorts of new antipsychotic users with evidence of severe mental illness (SMI, n = 5,621); dementia with behavioral symptoms (dementia + behavior) without SMI (n = 1,090); or delirium only without SMI or dementia + behavior (n = 2,100) were identified. MEASUREMENTS: Dose and duration of therapy with antipsychotics were assessed monthly with a 6-month look-back. Dose was measured as modified standardized daily dose (mSDD), with a mSDD of 1 or less considered below or at recommended maximum geriatric dose. Duration was categorized as 30 or fewer, 31 to 60, 61 to 90, and 91 to 184 days for SMI and dementia + behavior and 7 or fewer, 8 to 30, 31 to 90, and 91 to 184 days for delirium. Complementary log-log models with mSDD and duration as time-dependent variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: In all three groups, new antipsychotic users with a mSDD of 1 or less had significantly lower mortality risk (HRSMI  = 0.77, 95% CI = 0.67-0.88; HRdementia+behavior  = 0.52, 95% CI = 0.36-0.76; HRdelirium  = 0.61, 95% CI = 0.44-0.85) than peers with a mSDD greater than 1. Individuals with longer duration of antipsychotic use (91-184 days for SMI and delirium) had significantly lower mortality than those with a short duration of use (≤30 days for SMI; ≤7 days for delirium). The interaction between dose and duration was statistically significant in the SMI cohort (P < .001). CONCLUSION: Lower mortality was observed with within-recommended dose ranges for dementia + behavior, SMI, and delirium and with long duration of antipsychotic use for the latter two disease groups. Prescribers should monitor antipsychotic dosage throughout the course of antipsychotic treatment and customize dose and duration regimens to an individual's indications.

Recurring patterns in bacterioplankton dynamics during coastal spring algae blooms.

A process of global importance in carbon cycling is the remineralization of algae biomass by heterotrophic bacteria, most notably during massive marine algae blooms. Such blooms can trigger secondary blooms of planktonic bacteria that consist of swift successions of distinct bacterial clades, most prominently members of the Flavobacteriia, Gammaproteobacteria and the alphaproteobacterial Roseobacter clade. We investigated such successions during spring phytoplankton blooms in the southern North Sea (German Bight) for four consecutive years. Dense sampling and high-resolution taxonomic analyses allowed the detection of recurring patterns down to the genus level. Metagenome analyses also revealed recurrent patterns at the functional level, in particular with respect to algal polysaccharide degradation genes. We, therefore, hypothesize that even though there is substantial inter-annual variation between spring phytoplankton blooms, the accompanying succession of bacterial clades is largely governed by deterministic principles such as substrate-induced forcing.