Hybrid multimodal fusion for graph learning in disease prediction.

Graph neural networks (GNNs) have gained significant attention in disease prediction where the latent embeddings of patients are modeled as nodes and the similarities among patients are represented through edges. The graph structure, which determines how information is aggregated and propagated, plays a crucial role in graph learning. Recent approaches typically create graphs based on patients' latent embeddings, which may not accurately reflect their real-world closeness. Our analysis reveals that raw data, such as demographic attributes and laboratory results, offers a wealth of information for assessing patient similarities and can serve as a compensatory measure for graphs constructed exclusively from latent embeddings. In this study, we first construct adaptive graphs from both latent representations and raw data respectively, and then merge these graphs via weighted summation. Given that the graphs may contain extraneous and noisy connections, we apply degree-sensitive edge pruning and kNN sparsification techniques to selectively sparsify and prune these edges. We conducted intensive experiments on two diagnostic prediction datasets, and the results demonstrate that our proposed method surpasses current state-of-the-art techniques.

The occurrence of mental health symptoms in isotretinoin-treated adolescents.

BACKGROUND: Isotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in treated adolescents. METHODS: This retrospective cohort study using the Rochester Epidemiology Project identified 606 patients aged 12-18 prescribed isotretinoin over a 10-year period between January 1, 2008 and December 31, 2017. Medical records were reviewed to identify psychiatric diagnoses before and during isotretinoin therapy, as well as psychiatric symptoms not captured by formal diagnoses and changes to isotretinoin dosing because of psychiatric diagnoses or symptoms. RESULTS: One hundred seventy-seven (29.2%) had a psychiatric diagnosis prior to isotretinoin initiation, but 98 (16.2%) had a new psychiatric diagnosis or psychiatric symptom while taking isotretinoin. Patients with a psychiatric history were no more likely than those without to receive a new psychiatric diagnosis during treatment (4.5% vs. 3.7%; p = .650), but did experience more psychiatric symptoms, primarily low mood and mood swings (23.7% vs. 7.7%; p < .001). Only 25.5% of the 98 with a new psychiatric diagnosis or psychiatric symptom had a subsequent dose change. A dose change was more likely if patients received a new psychiatric diagnosis (41.7% vs. 20.3%; p = .037) or patients did not have a psychosocial explanation for psychiatric symptoms (34.4% vs. 10.8%; p = .009). CONCLUSIONS: A substantial proportion of adolescent patients prescribed isotretinoin had a prior psychiatric diagnosis. This predicts more psychiatric symptoms during isotretinoin treatment. Adolescents with a psychiatric history who have worsening symptoms and those with new-onset psychiatric symptoms would benefit from close monitoring while taking isotretinoin.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. RESULTS: Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. CONCLUSION: Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Use of Gabapentin for Alcohol Withdrawal Syndrome in the Hospital Setting: A Randomized Open-Label Controlled Trial.

Background/objectives: Patients hospitalized with alcohol withdrawal syndrome (AWS) are typically treated with CIWA-directed benzodiazepines to prevent complications, such as seizures and delirium tremens. Gabapentin is an evidence-based alternative to benzodiazepines in the outpatient setting, but there is limited data for hospitalized patients with AWS. This study compared fixed-dose gabapentin to CIWA-directed benzodiazepines for AWS in the hospital setting. Methods: This open-label, randomized controlled trial enrolled 88 adults from February 1, 2017 to August 16, 2020 with a risk of complicated alcohol withdrawal as defined by the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) ≥4. Patients were randomized within 16 h of admission to either fixed-dose gabapentin taper or continued CIWA-directed benzodiazepine administration. The primary outcome was the length of stay (LOS). Secondary outcomes included seizure, delirium tremens, ICU transfer, and patient-reported symptoms (alcohol cravings, anxiety, sleepiness). Results: LOS was shorter, but not statistically different in the gabapentin group compared to the benzodiazepine group. Because benzodiazepines were received in both gabapentin and benzodiazepine groups before randomization, the mean amount of benzodiazepines received in each group was also not statistically different, although the amount received by the gabapentin group was less than half of that received by the benzodiazepine group (4.3 vs. 10.6 mg, p = 0.146 by per protocol analysis). There were no statistical differences in secondary measures. Conclusions: Fixed-dose gabapentin taper showed similar outcomes compared to CIWA-directed benzodiazepines for the treatment of hospitalized patients with mild/moderate AWS, but the interpretation of the results is limited due to under-enrollment and the use of benzodiazepines in both groups pre-enrollment.Clinical trial registration: NCT03012815.

Self-Reported Injuries in Indoor Gym-Based Rock Climbers: A Retrospective Study of Predictors of Prolonged Injury and Seeking Medical Care.

INTRODUCTION: Indoor climbing injuries are often related to overuse, and climbers choose between self-management and seeing a medical practitioner. This study evaluated predictors of prolonged injury and seeking medical care for indoor climbing injuries. METHODS: A convenience sample of adult climbers from 5 gyms in New York City was interviewed about injuries over the past 3 y, because of which they stopped climbing for at least a week or saw a medical practitioner. RESULTS: In total, 122 of 284 (43%) participants had at least 1 injury, for a total of 158 injuries. Fifty (32%) were prolonged, lasting at least 12 wk. Predictors of prolonged injury included older age (odds ratio [OR], 2.28, per 10-y increase; 95% CI, 1.31-3.96), hours per week spent climbing (OR, 1.14, per 1-h increase; 95% CI, 1.06-1.24), climbing difficulty (OR, 2.19, per difficulty group increase; 95% CI, 1.31-3.66), and years of climbing experience (OR, 3.99, per 5-y increase; 95% CI, 1.61-9.84). Only 38% of injuries were seen by a medical practitioner. Predictors of seeking care included prolonged injury (OR, 3.04; 95% CI, 1.39-6.64) and rope climbing preference (OR, 1.98; 95% CI, 1.02-3.82). The most common theme for seeking care was serious pain or interference with climbing or daily activities. CONCLUSIONS: Despite prolonged injuries being common, especially in older, more experienced, and higher-level climbers, only a third of climbers with injuries seek medical care. Outside of injuries causing minimal pain or limitation, those who self-managed reported receiving advice from other climbers or online research as a prominent reason for that choice.

A Guide to Indoor Rock Climbing Injuries.

ABSTRACT: Rock climbing is an increasingly popular indoor sport with a sizable risk of overuse injuries. Yet, many medical practitioners have little familiarity with evaluating and treating climbing injuries because of the terminology, biomechanical demands, mechanisms of injury, and return to sport counseling needed, unique to the sport. This review seeks to educate practitioners on these aspects. Upper extremity injuries occur more frequently than lower extremity injuries, with finger injuries being most prevalent. Pulley injuries, consisting of rupture of the A2 or A4 annular pulleys are the most common type of injury. Other finger injuries include tenosynovitis of the flexor tendons, as well as lumbrical muscle tears. Elbow injuries occur frequently, with medial epicondylopathy being most common. Brachialis injuries are seldom seen outside of climbing. Lower-extremity injuries are typically more acute in nature, including ankle injuries from falls and knee injuries from strenuous climbing moves.

Is Ocean Acidification Really a Threat to Marine Calcifiers? A Systematic Review and Meta-Analysis of 980+ Studies Spanning Two Decades.

Ocean acidification is considered detrimental to marine calcifiers, but mounting contradictory evidence suggests a need to revisit this concept. This systematic review and meta-analysis aim to critically re-evaluate the prevailing paradigm of negative effects of ocean acidification on calcifiers. Based on 5153 observations from 985 studies, many calcifiers (e.g., echinoderms, crustaceans, and cephalopods) are found to be tolerant to near-future ocean acidification (pH ≈ 7.8 by the year 2100), but coccolithophores, calcifying algae, and corals appear to be sensitive. Calcifiers are generally more sensitive at the larval stage than adult stage. Over 70% of the observations in growth and calcification are non-negative, implying the acclimation capacity of many calcifiers to ocean acidification. This capacity can be mediated by phenotypic plasticity (e.g., physiological, mineralogical, structural, and molecular adjustments), transgenerational plasticity, increased food availability, or species interactions. The results suggest that the impacts of ocean acidification on calcifiers are less deleterious than initially thought as their adaptability has been underestimated. Therefore, in the forthcoming era of ocean acidification research, it is advocated that studying how marine organisms persist is as important as studying how they perish, and that future hypotheses and experimental designs are not constrained within the paradigm of negative effects.

Shark teeth can resist ocean acidification.

Ocean acidification can cause dissolution of calcium carbonate minerals in biological structures of many marine organisms, which can be exacerbated by warming. However, it is still unclear whether this also affects organisms that have body parts made of calcium phosphate minerals (e.g. shark teeth), which may also be impacted by the 'corrosive' effect of acidified seawater. Thus, we examined the effect of ocean acidification and warming on the mechanical properties of shark teeth (Port Jackson shark, Heterodontus portusjacksoni), and assessed whether their mineralogical properties can be modified in response to predicted near-future seawater pH (-0.3 units) and temperature (+3°C) changes. We found that warming resulted in the production of more brittle teeth (higher elastic modulus and lower mechanical resilience) that were more vulnerable to physical damage. Yet, when combined with ocean acidification, the durability of teeth increased (i.e. less prone to physical damage due to the production of more elastic teeth) so that they did not differ from those raised under ambient conditions. The teeth were chiefly made of fluorapatite (Ca5 (PO4 )3 F), with increased fluoride content under ocean acidification that was associated with increased crystallinity. The increased precipitation of this highly insoluble mineral under ocean acidification suggests that the sharks could modulate and enhance biomineralization to produce teeth which are more resistant to corrosion. This adaptive mineralogical adjustment could allow some shark species to maintain durability and functionality of their teeth, which underpins a fundamental component of predation and sustenance of the trophic dynamics of future oceans.

The Modernization of Clozapine: A Recapitulation of the Past in the United States and the View Forward.

PURPOSE: Although clozapine was Food and Drug Administration (FDA) approved more than 3 decades ago, major barriers and gaps in knowledge continue to prevent its effective and safe use. We review modern-day problems encountered with clozapine in the United States (US). METHODS: Information surrounding current administrative, clinical, research, and technological gaps or barriers related to clozapine use in the US was reviewed. FINDINGS: The history of how clozapine became FDA approved likely contributes to gaps in knowledge. The frequency of safety warnings added to the FDA prescribing information may add to fears about clozapine, as evidence by numerous published survey studies. The clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been modified several times in the last decade, causing access and safety issues for patients, which are discussed. Evidence may suggest that the FDA REMS requirements for hematologic monitoring are too cumbersome, and there may be ability to safely loosen requirements. The COVID-19 pandemic brought forth the ability for extended interval monitoring but also greater awareness of the clozapine-inflammation interaction. Newer guidelines published describe considerations in personalizing clozapine titration based on principles of ethnopsychopharmacology. Emerging technologies to support the use of clozapine are not widely available. IMPLICATIONS: Clozapine is a unique life-saving drug but it is underused in the US, despite its established efficacy. The 2021 REMS changes led to significant difficulties for providers and patients. We highlight the importance of the clozapine-inflammation interaction, therapeutic drug monitoring, and the ability for individual care based on patient-specific factors. There is an urgent need for advancing technology used for clozapine monitoring, evaluating barriers created by REMS, and establishing consistent practices throughout the US.

Iatrogenic clozapine intoxication after hospital admission: A case-based rationale for an inpatient pharmacy clozapine monitoring service.

BACKGROUND: Clozapine must be retitrated after 2 consecutive days or more of missed doses owing to the risk of severe hypotension, bradycardia, and cardiac arrest. However, other important adverse events such as somnolence, sialorrhea, or respiratory depression can occur without severe cardiovascular sequalae. These other unintended consequences are not well characterized in the literature. Three cases are reported, highlighting the concerns for continuing clozapine without retitration after periods of not taking the medication. Implications are discussed as well as how pharmacists can collaborate with other disciplines to mitigate safety risks associated with clozapine for hospitalized patients. CASE SUMMARIES: The first case highlights the importance of medication reconciliation and verifying adherence before clozapine continuation in the hospital. Waiting for collateral information and missing one dose are safer than unknowingly resuming clozapine. The second case suggests that it may be safer to consider patients with unexplained worsening psychiatric symptoms as nonadherent and even partially reduced clozapine doses after nonadherence may be unsafe. The final case demonstrates the importance assessing comedications (e.g., warfarin, phenytoin) that have available therapeutic drug monitoring to suggest nonadherence. Each case resulted in significant adverse events requiring transfer to a higher level of care or prolonged hospitalization. PRACTICE IMPLICATIONS: Continuation of psychiatric medications when a patient is admitted to the hospital is important to prevent worsening of symptoms. However, assessment of clozapine adherence and confidence in that assessment is crucial to prevent clozapine intoxication, severe hypotension, and even death. Pharmacists are uniquely positioned to assess clozapine adherence and ensure patient safety. A hospital-based service was created at a 2000-bed academic medical center to improve transitions of care when patients are admitted with clozapine. The process was created in collaboration with the psychiatric consultation service. Through this process, pharmacists also complete appropriate hematologic monitoring and ongoing clinical monitoring for adverse events.

Improvement of Inpatient Psychiatric Facility Quality Reporting program measure: Screening for metabolic disorders through pharmacy collaborative practice agreement.

BACKGROUND: Second-generation antipsychotics are associated with lower risks of extrapyramidal symptoms, including tardive dyskinesia. However, many second-generation antipsychotics are associated with metabolic adverse effects, including weight gain, impaired blood glucose control, and hyperlipidemia. Metabolic monitoring for patients prescribed antipsychotic medication is 1 of several measures of the Centers for Medicare & Medicaid Services' Inpatient Psychiatric Facility Quality Reporting program. Screening for metabolic disorders (SMD) must be obtained within the previous 365 days before the hospital discharge date. National data suggest that compliance with this measure is low. OBJECTIVE: To improve compliance of metabolic monitoring by 20% while ensuring that the quality improvement interventions did not cause any unintended adverse effects on other aspects of our system. PRACTICE DESCRIPTION: This quality initiative was conducted at a large, 2000-bed academic medical center with approximately 80 inpatient psychiatric beds. PRACTICE INNOVATION: To improve the metabolic screening rates, a pharmacist collaborative practice agreement (CPA) was established as part of a quality improvement project. Previously, there were no formal processes at the institution to ensure that appropriate laboratory tests were conducted. EVALUATION METHODS: Using an uncontrolled before-and-after design, SMD data were gathered from 6 months before and 6 months after CPA implementation. Pearson chi-square test or Fisher exact test were used to compare the pre- and postintervention groups in this quasi-experimental design. RESULTS: Compared with the preintervention period, compliance of SMD monitoring increased by 21.2% in the postintervention phase-from 69.2% to 90.4% (P < 0.001). CONCLUSION: The empowerment of clinical pharmacists with a CPA significantly improved guideline-concordant metabolic monitoring of antipsychotics. These findings may have significant impact on the approach to the safe use of these essential psychotropic medications and provide a framework for other inpatient mental health facilities to optimally use the skills of their interdisciplinary team.

Calcifiers can Adjust Shell Building at the Nanoscale to Resist Ocean Acidification.

Ocean acidification is considered detrimental to marine calcifiers based on laboratory studies showing that increased seawater acidity weakens their ability to build calcareous shells needed for growth and protection. In the natural environment, however, the effects of ocean acidification are subject to ecological and evolutionary processes that may allow calcifiers to buffer or reverse these short-term negative effects through adaptive mechanisms. Using marine snails inhabiting a naturally CO2 -enriched environment over multiple generations, it is discovered herein that they build more durable shells (i.e., mechanically more resilient) by adjusting the building blocks of their shells (i.e., calcium carbonate crystals), such as atomic rearrangement to reduce nanotwin thickness and increased incorporation of organic matter. However, these adaptive adjustments to future levels of ocean acidification (year 2100) are eroded at extreme CO2 concentrations, leading to construction of more fragile shells. The discovery of adaptive mechanisms of shell building at the nanoscale provides a new perspective on why some calcifiers may thrive and others collapse in acidifying oceans, and highlights the inherent adaptability that some species possess in adjusting to human-caused environmental change.

Norethindrone alters mating behaviors, ovary histology, hormone production and transcriptional expression of steroidogenic genes in zebrafish (Danio rerio).

The impact of progestins (i.e. synthetic forms of progesterone) on aquatic organisms has drawn increasing attention due to their widespread occurrence in the aquatic environments and potential effects on the endocrine system of fish. In this study, the effects of norethindrone (NET, a progestin) on the reproductive behavior, sex hormone production and transcriptional expressions were evaluated by exposing female zebrafish to NET at 0, 3.1, 36.2 and 398.6 ng L-1 for 60 days. Results showed that NET impaired the mating behaviors of female at 36.2 and 398.6 ng L-1 exhibited by males and increased the frequency of atretic follicular cells in the ovary exposed to NET at 398.6 ng L-1. As for sex hormones, plasma testosterone concentration in zebrafish increased, while estradiol concentration decreased. Up-regulation of genes (Npr, Mpra, Mprß, Fshß, Lß, Tshb, Nis and Dio2) was detected in the brain of fish exposed to NET at 398.6 ng L-1. The transcriptional levels of genes (Esr1, Vtg1, Ar, Cyp19a, Cyp11b and Ptgs2) were generally inhibited in the ovary of zebrafish by NET at 398.6 ng L-1. Moreover, the transcripts of genes (Vtg1, Esr1, Ar and Pgr) in the liver were reduced by NET at 36.2 and 398.6 ng L-1. Our findings suggest that NET can potentially diminish the of fish populations not only by damaging their reproductive organs, but also by altering their mating behavior through the changes in the expressions of genes responsible for the production of sex hormones.

How calorie-rich food could help marine calcifiers in a CO2-rich future.

Increasing carbon emissions not only enrich oceans with CO2 but also make them more acidic. This acidifying process has caused considerable concern because laboratory studies show that ocean acidification impairs calcification (or shell building) and survival of calcifiers by the end of this century. Whether this impairment in shell building also occurs in natural communities remains largely unexplored, but requires re-examination because of the recent counterintuitive finding that populations of calcifiers can be boosted by CO2 enrichment. Using natural CO2 vents, we found that ocean acidification resulted in the production of thicker, more crystalline and more mechanically resilient shells of a herbivorous gastropod, which was associated with the consumption of energy-enriched food (i.e. algae). This discovery suggests that boosted energy transfer may not only compensate for the energetic burden of ocean acidification but also enable calcifiers to build energetically costly shells that are robust to acidified conditions. We unlock a possible mechanism underlying the persistence of calcifiers in acidifying oceans.

Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients.

Although nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity, around 10%-20% of nonobese Americans and Asians still develop NAFLD. Data on this special group are limited. We therefore studied the severity and clinical outcomes of nonobese NAFLD patients. Consecutive NAFLD patients who underwent liver biopsy were prospectively recruited. We used the NASH Clinical Research Network system to score the histology. The Asian body mass index cutoff of 25 kg/m2 was used to define nonobese NAFLD. Among 307 recruited NAFLD patients, 72 (23.5%) were nonobese. Compared to obese patients, nonobese patients had lower NAFLD activity score (3.3 ± 1.3 vs. 3.8 ± 1.2; P = 0.019), mainly contributed by steatosis (1.7 ± 0.8 vs. 2.0 ± 0.8; P = 0.014) and presence of hepatocyte ballooning (60.9% vs. 73.4%; P = 0.045). Similarly, nonobese patients had lower fibrosis stage (1.3 ± 1.5 vs. 1.7 ± 1.4; P = 0.004), serum cytokeratin-18 fragments (283 vs. 404 U/L; P < 0.001) and liver stiffness measurement by transient elastography (6.3 vs. 8.6 kilopascals; P < 0.001). By multivariate analysis in nonobese patients, only elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio [OR], 1.644; P = 0.021), whereas elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; P = 0.025). After a median follow-up of 49 months, 6 patients died, 2 developed hepatocellular carcinoma, and 1 had liver failure, all of whom were in the obese group. CONCLUSION: Nonobese NAFLD patients tend to have less-severe disease and may have a better prognosis than obese patients. Hypertriglyceridemia and higher creatinine are the key factors associated with advanced liver disease in nonobese patients. (Hepatology 2017;65:54-64).

Use of a Gabapentin Protocol for the Management of Alcohol Withdrawal: A Preliminary Experience Expanding From the Consultation-Liaison Psychiatry Service.

BACKGROUND: Benzodiazepines are the conventional mainstay to manage alcohol withdrawal; however, patients are subsequently at increased risk for poor sleep, cravings, and return to drinking. Research on alternative pharmacologic agents to facilitate safe alcohol withdrawal is scant. Gabapentin is one medication shown in small studies to reduce the need for benzodiazepines in the setting of alcohol withdrawal. The continuation of gabapentin after alcohol withdrawal appears to be safe during early sobriety and may aid in reducing alcohol-related cravings or returning to alcohol consumption. Use of a gabapentin-based, benzodiazepine-sparing protool began in early 2015 by the Mayo Clinic, Rochester, Consultation-Liaison Psychiatry Service. OBJECTIVE: A retrospective chart review was conducted to detect any safety concerns with use of a gabapentin protocol for alcohol withdrawal syndrome. METHODS: Secondary outcomes were derived by comparing a matched cohort of patients who received benzodiazepines for alcohol withdrawal syndrome. RESULTS: Seventy-seven patients had their alcohol withdrawal managed via a gabapentin protocol during the study period. No patients required transfer to a higher level of care or had a documented withdrawal seizure. Length of stay between the gabapentin protocol group and benzodiazepine group were similar. CONCLUSION: This preliminary data has supported the frequent use of this protocol in the general internal medicine practice and formalization of an institutional order set of this protocol for mild to moderate alcohol withdrawal syndrome. Prospective studies are required to validate findings.

Testing for thresholds of ecosystem collapse in seagrass meadows.

Although the public desire for healthy environments is clear-cut, the science and management of ecosystem health has not been as simple. Ecological systems can be dynamic and can shift abruptly from one ecosystem state to another. Such unpredictable shifts result when ecological thresholds are crossed; that is, small cumulative increases in an environmental stressor drive a much greater change than could be predicted from linear effects, suggesting an unforeseen tipping point is crossed. In coastal waters, broad-scale seagrass loss often occurs as a sudden event associated with human-driven nutrient enrichment (eutrophication). We tested whether the response of seagrass ecosystems to coastal nutrient enrichment is subject to a threshold effect. We exposed seagrass plots to different levels of nutrient enrichment (dissolved inorganic nitrogen) for 10 months and measured net production. Seagrass response exhibited a threshold pattern when nutrient enrichment exceeded moderate levels: there was an abrupt and large shift from positive to negative net leaf production (from approximately 0.04 leaf production to 0.02 leaf loss per day). Epiphyte load also increased as nutrient enrichment increased, which may have driven the shift in leaf production. Inadvertently crossing such thresholds, as can occur through ineffective management of land-derived inputs such as wastewater and stormwater runoff along urbanized coasts, may account for the widely observed sudden loss of seagrass meadows. Identification of tipping points may improve not only adaptive-management monitoring that seeks to avoid threshold effects, but also restoration approaches in systems that have crossed them.

Mineralogical Plasticity Acts as a Compensatory Mechanism to the Impacts of Ocean Acidification.

Calcifying organisms are considered particularly susceptible to the future impacts of ocean acidification (OA), but recent evidence suggests that they may be able to maintain calcification and overall fitness. The underlying mechanism remains unclear but may be attributed to mineralogical plasticity, which modifies the energetic cost of calcification. To test the hypothesis that mineralogical plasticity enables the maintenance of shell growth and functionality under OA conditions, we assessed the biological performance of a gastropod (respiration rate, feeding rate, somatic growth, and shell growth of Austrocochlea constricta) and analyzed its shell mechanical and geochemical properties (shell hardness, elastic modulus, amorphous calcium carbonate, calcite to aragonite ratio, and magnesium to calcium ratio). Despite minor metabolic depression and no increase in feeding rate, shell growth was faster under OA conditions, probably due to increased precipitation of calcite and trade-offs against inner shell density. In addition, the resulting shell was functionally suitable for increasingly "corrosive" oceans, i.e., harder and less soluble shells. We conclude that mineralogical plasticity may act as a compensatory mechanism to maintain overall performance of calcifying organisms under OA conditions and could be a cornerstone of calcifying organisms to acclimate to and maintain their ecological functions in acidifying oceans.