Analysis of Hepatitis D Virus in Minor Salivary Gland of Sjögren's Disease.

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.

Suicide Risk During COVID-19: Correlates of Peri-pandemic Suicidal Ideation Controlling for Pre-pandemic Ideation.

Suicide is a public health concern which warrants considerable attention, especially with the onset of the COVID-19 pandemic. The current study sought to examine the relationship between behavioral, psychological, and economic impacts of COVID-19 on suicidal ideation severity in a sample of 90 undergraduate students who completed a comprehensive survey on mental health in January 2020 and were re-assessed in April, June, and July of 2020. Multiple regression analyses showed that changes in experience of loneliness, loneliness due to social distancing, pandemic-related concerns, COVID contagion anxiety, and quarantining alone positively and significantly correlated with peri-pandemic suicidal ideation severity after accounting for pre-pandemic suicidal ideation and sexual orientation, while time spent talking to romantic partner and time spent talking to friends and family were negatively correlated. Findings provide insights into the psychological and behavioral effects of social distancing measures and the pandemic, but further research is needed to generalize findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s41811-022-00140-2.

Building knowledge, optimising physical and mental health and setting up healthier life trajectories in South African women (Bukhali): a preconception randomised control trial part of the Healthy Life Trajectories Initiative (HeLTI).

INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs. METHODS AND ANALYSIS: Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18-28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871). PROTOCOL VERSION: 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.

Changes in Sleep Problems Across Attention-Deficit/Hyperactivity Disorder Treatment: Findings from the Multimodal Treatment of Attention-Deficit/Hyperactivity Disorder Study.

Objective: Stimulant medication and behavior therapy are efficacious for youth with attention-deficit/hyperactivity disorder (ADHD). However, research suggests that stimulants may start and/or worsen sleep problems for youth. Further, the impact of behavior therapy for ADHD on sleep is unknown. This study examined the frequency of sleep problems and effects of stimulant medication, behavior therapy, and their combination on sleep problems in youth with ADHD. This study also explored the influence of dimensional baseline ratings of ADHD symptom subtype and psychiatric comorbidity on sleep outcomes. Methods: Participants were 576 children (aged 7-9 years) with ADHD-Combined type from the Multimodal Treatment of ADHD study that compared methylphenidate, behavior therapy, and their combination to community care. Before treatment, parents completed the Child Behavior Checklist used to derive a total sleep problems score. Parents also completed ratings of oppositionality and ADHD symptom severity, whereas youth completed ratings of depression and anxiety. These ratings were readministered after treatment. Results: General linear mixed-effects models were used to assess change in total sleep problems across treatment. The combined group exhibited a statistically significant reduction in total sleep problems (z = -5.81, p < 0.001). Reductions in total sleep problems in methylphenidate (z = -3.11, p = 0.05), behavior therapy (z = -2.99, p = 0.08), or community care (z = -1.59, p > 0.99) did not reach statistical significance. Change in psychiatric symptoms did not significantly moderate change in total sleep problems by treatment assignment. Greater baseline oppositional defiant disorder severity predicted less reduction in total sleep problems, χ2(1) = 3.86, p < 0.05. Conclusions: Findings suggest that combination of methylphenidate and behavior therapy is efficacious for reducing parent-reported sleep problems in young children with ADHD-Combined type relative to community care. However, potential ameliorative effects of monotherapy treatments (i.e., methylphenidate, behavior therapy) should be examined. Future replication is needed to confirm findings.

The association between suicidal ideation and lifetime suicide attempts is strongest at low levels of depression.

Suicidal ideation and depression alone are poor predictors of subsequent engagement in suicidal behavior. Evidence suggests, however, that the lethargy associated with depression may serve as a protective factor against suicide attempts. The purpose of this study was to examine whether suicidal ideation and depression symptoms interact in relation to lifetime suicide attempts among a sample of psychiatric outpatients. A sample of 739 psychiatric outpatients (Mage = 27.26, 60.8% female, 73.3% White/European American) from a university-affiliated clinic completed a battery of self-report measures prior to their initial intake appointments. Consistent with hypotheses, a significant interaction emerged between suicidal ideation and depression symptoms in association with lifetime suicide attempts, such that the relationship between suicidal ideation and lifetime suicide attempts was strongest at low, as opposed to high, levels of depression. These findings align with previous research suggesting that lethargy may be a protective factor against suicide attempts, and conversely, that heightened arousal may serve as a suicide risk factor. Our results also point to a configuration of suicidal ideation and depression symptoms that might reflect higher suicide risk.

Thwarted Belongingness in Relation to Face-to-Face and Online Interactions.

Suicide is ranked as the tenth leading cause of death for all ages in the United States (Centers for Disease Control and Prevention, 2012). Joiner's (2005) interpersonal theory of suicide stated thwarted belongingness-the feeling of being alienated from others-and perceived burdensomeness-the feeling of being a liability to others-are the primary proximal factors leading to suicidal desire. The current study focused on thwarted belongingness and examined its relationship to face-to-face interactions and online interactions in both an undergraduate and community sample. We hypothesized that negative face-to-face and online interactions would be independently associated with higher levels of thwarted belongingness. Furthermore, we hypothesized that face-to-face interactions would moderate the relationship between online interactions and thwarted belongingness and that online interactions would moderate the relationship between face-to-face interactions and thwarted belongingness. Three hundred eighty-seven participants (79.6% female) at a southern university and 209 (62.7% male) participants recruited from Amazon's Mechanical Turk website completed an online survey. Results only partially supported hypotheses, with only face-to-face interactions shown to be independently related to higher levels of thwarted belongingness. These findings indicated that negative face-to-face interactions may contribute to higher levels of risk factors for suicide ideation and highlighted the importance of assessing for negative interactions across all contexts.

Initial validation of brief measures of suicide risk factors: Common data elements used by the Military Suicide Research Consortium.

The Military Suicide Research Consortium (MSRC) developed a 57-item questionnaire assessing suicide risk factors, referred to as the Common Data Elements (CDEs), in order to facilitate data sharing and improve collaboration across independent studies. All studies funded by MSRC are required to include the CDEs in their assessment protocol. The CDEs include shortened measures of the following: current and past suicide risk, lethality and intent of past suicide attempts, hopelessness, thwarted belongingness, anxiety sensitivity, posttraumatic stress disorder symptoms, traumatic brain injury, insomnia, and alcohol abuse. This study aimed to evaluate the psychometric properties of the CDE items drawn from empirically validated measures. Exploratory factor analysis was used to examine the overall structure of the CDE items, and confirmatory factor analyses were used to evaluate the distinct properties of each scale. Internal consistencies of the CDE scales and correlations with full measures were also examined. Merged data from 3,140 participants (81.0% military service members, 75.6% male) across 19 MSRC-funded studies were used in analyses. Results indicated that all measures exhibited adequate internal consistency, and all CDE shortened measures were significantly correlated with the corresponding full measures with moderate to strong effect sizes. Factor analyses indicated that the shortened CDE measures performed well in comparison with the full measures. Overall, our findings suggest that the CDEs are not only brief but also provide psychometrically valid scores when assessing suicide risk and related factors that may be used in future research. (PsycINFO Database Record

The interpersonal theory of suicide: A systematic review and meta-analysis of a decade of cross-national research.

Over the past decade, the interpersonal theory of suicide has contributed to substantial advances in the scientific and clinical understanding of suicide and related conditions. The interpersonal theory of suicide posits that suicidal desire emerges when individuals experience intractable feelings of perceived burdensomeness and thwarted belongingness and near-lethal or lethal suicidal behavior occurs in the presence of suicidal desire and capability for suicide. A growing number of studies have tested these posited pathways in various samples; however, these findings have yet to be evaluated meta-analytically. This paper aimed to (a) conduct a systematic review of the unpublished and published, peer-reviewed literature examining the relationship between interpersonal theory constructs and suicidal thoughts and behaviors, (b) conduct meta-analyses testing the interpersonal theory hypotheses, and (c) evaluate the influence of various moderators on these relationships. Four electronic bibliographic databases were searched through the end of March, 2016: PubMed, Medline, PsycINFO, and Web of Science. Hypothesis-driven meta-analyses using random effects models were conducted using 122 distinct unpublished and published samples. Findings supported the interpersonal theory: the interaction between thwarted belongingness and perceived burdensomeness was significantly associated with suicidal ideation; and the interaction between thwarted belongingness, perceived burdensomeness, and capability for suicide was significantly related to a greater number of prior suicide attempts. However, effect sizes for these interactions were modest. Alternative configurations of theory variables were similarly useful for predicting suicide risk as theory-consistent pathways. We conclude with limitations and recommendations for the interpersonal theory as a framework for understanding the suicidal spectrum. (PsycINFO Database Record

Sex Differences in Suicide-Related Symptoms in a Large Military Sample.

Little research has focused on suicide-related symptoms in female servicemembers, despite high rates of suicidal behaviors. This study examined sex differences in suicide-related risk factors in 3,374 U.S. Army Recruiters (91.9% male). Female servicemembers had a greater number of past major depressive and suicidal ideation episodes than males; there were no differences in suicide attempt histories or mental health visits. Females reported significantly fewer symptoms of current suicidal ideation, perceived burdensomeness, and acquired capability. No significant sex differences emerged for thwarted belongingness, insomnia, or agitation. Our findings provide evidence for sex differences in rates of suicide-related symptoms among military personnel.

Cross-cultural relevance of the Interpersonal Theory of suicide across Korean and U.S. undergraduate students.

This study investigated the cross-cultural relevance and validity of the Interpersonal Theory of Suicide (ITS) utilizing young adult samples from South Korea (n =554) and the United States (U.S.; n =390). To examine the ITS, all participants completed self-report questionnaires measuring Thwarted Belongingness, Perceived Burdensomeness, and Capability for Suicide. We examined whether each construct significantly predicted the severity of suicidal risk in both samples. We also determined whether the strength of the effects of Thwarted Belongingness and Perceived Burdensomeness on suicidal ideation differed between the two samples due to the greater degree of importance placed on interpersonal relationships in collectivistic cultures such as South Korea. Structural equation modeling was used to examine these hypotheses. Thwarted Belongingness, Perceived Burdensomeness, and Capability for Suicide significantly predicted elevated suicidal risk. However, there were no significant differences in the paths from Thwarted Belongingness or Perceived Burdensomeness to suicide risk between the South Korean and U.S. SAMPLES: These findings support the cross-cultural relevance and applicability of the ITS, whereby Thwarted Belongingness and Perceived Burdensomeness serve as indicators of suicide risk in both Western (U.S.) and East Asian (Korean) samples.

Examination of MMPI-2-RF Substantive Scales as Indicators of Acute Suicidal Affective Disturbance Components.

A new suicide-specific diagnostic entity, acute suicidal affective disturbance (ASAD), was recently proposed to fill a void in the nomenclature. Although several studies have examined the reliability, validity, and potential clinical utility of ASAD, no studies have examined personality indicators of ASAD. This study sought to examine the association between personality and psychopathology factors, as assessed by the Minnesota Multiphasic Personality Inventory-2-Revised Form (MMPI-2-RF), and constructs that comprise ASAD in a sample of 554 psychiatric outpatients who completed all measures prior to their intake appointments. A smaller subset of patients (N = 58) also completed a measure designed to assess lifetime ASAD symptoms. Results indicated that ASAD symptoms were associated with traits characterized by emotional turmoil and atypical cognitive processes. Further, suicide-related criteria that comprise ASAD were related to low positive emotionality and hopelessness, whereas the overarousal criteria were associated with somatic symptoms and an inability to tolerate frustration and stress. These findings expand on previous research that examines the convergent and discriminant validity of ASAD and could inform clinical treatment by providing insight into personality traits that might be associated with acute suicide risk.

Insomnia and suicide-related behaviors: A multi-study investigation of thwarted belongingness as a distinct explanatory factor.

BACKGROUND: Insomnia is a robust correlate of suicidal ideation and behavior. Preliminary research has identified thwarted belongingness (c.f. social disconnection) as an explanatory link between insomnia and suicidal ideation. OBJECTIVES: This study replicates and extends previous findings using both cross-sectional and longitudinal designs in four demographically diverse samples. Additionally, the specificity of thwarted belongingness was evaluated by testing anxiety as a rival mediator. METHOD: Self-report measures of insomnia symptoms, thwarted belongingness, suicidal ideation and behavior, and anxiety were administered in four adult samples: 469 undergraduate students, 352 psychiatric outpatients, 858 firefighters, and 217 primary care patients. RESULTS: More severe insomnia was associated with more severe thwarted belongingness and suicidality. Thwarted belongingness significantly accounted for the association between insomnia and suicidality, cross-sectionally and longitudinally, beyond anxiety. Notably, findings supported the specificity of thwarted belongingness: anxiety did not significantly mediate the association between insomnia and suicidality, and insomnia did not mediate the relation between thwarted belongingness and suicidality. LIMITATIONS: This study relied solely on self-report measures. Future studies incorporating objective sleep measurements are needed. CONCLUSION: Findings underscore the utility of assessing and addressing sleep disturbances and social disconnection to reduce suicide risk.

A meta-analytic review of the association between agitation and suicide attempts.

Agitation has been implicated as an acute risk factor for suicidal behavior, yet the literature to date has not been consolidated to better understand this relationship. We conducted a meta-analysis of the association between agitation and suicidal behavior to synthesize the existing literature (k=13 studies) and point out future directions for research. Results indicated that the association between agitation and suicidal behavior is moderate (Hedge's g=0.40, p=0.007, 95% CI [0.08, 0.72]). Follow-up meta-regressions revealed that age, gender, and year of publication were not significant moderators of the magnitude of this relationship. However, there was evidence of publication bias, as shown by a funnel plot and Egger's test. These findings suggest the importance of future research that examines the nature of the association between agitation and suicidal behavior longitudinally and with novel research designs, as implications for clinical practice and suicide risk assessment may be substantial.

Mental Health Service Use Among Firefighters With Suicidal Thoughts and Behaviors.

OBJECTIVE: This study aimed to characterize rates and correlates of mental health service use, as well as barriers to care, among a sample of firefighters reporting a history of suicide ideation, plans, or attempts during their firefighting careers. METHODS: Participants (N=483) completed a Web-based survey assessing history of suicidal thoughts and behaviors, prior mental health service utilization, and barriers to treatment. RESULTS: Overall, 77% of participants reported receipt of mental health services during their firefighting careers (attempt history, 93%; plan but no attempt, 77%; and ideation only 68%). Firefighters with fewer years of service were less likely than those with more years to have accessed treatment. Service nonusers were more likely than service users to report concerns regarding reputation and embarrassment as barriers to care. CONCLUSIONS: Findings from this preliminary investigation suggest that the majority of firefighters with a history of elevated suicide risk have received mental health services.

Is Insomnia Lonely? Exploring Thwarted Belongingness as an Explanatory Link between Insomnia and Suicidal Ideation in a Sample of South Korean University Students.

STUDY OBJECTIVES: Suicide is a serious public health problem, and suicide rates are particularly high in South Korea. Insomnia has been identified as a risk factor for suicidal ideation; however, little is known about the mechanisms accounting for this relationship in this population. Based on the premise that insomnia can be lonely (e.g., being awake when everyone else is asleep), the purpose of this study was to examine whether greater insomnia severity would be associated with higher levels of thwarted belongingness and suicidal ideation, and whether thwarted belongingness would mediate the relationship between insomnia and suicidal ideation. METHODS: Predictions were tested in a sample of 552 South Korean young adults who completed self-report measures of insomnia severity, suicidal ideation, and thwarted belongingness. RESULTS: Greater insomnia symptom severity was significantly and positively associated with thwarted belongingness and suicidal ideation. Mediation analyses revealed that thwarted belongingness significantly accounted for the relationship between insomnia severity and suicidal ideation. CONCLUSIONS: These findings highlight the potential importance of monitoring and therapeutically impacting insomnia and thwarted belongingness to help reduce suicide risk.

A Preliminary Examination of the Relationship Between Social Networking Interactions, Internet Use, and Thwarted Belongingness.

BACKGROUND: Joiner's (2005) interpersonal-psychological theory of suicide hypothesizes that suicidal desire develops in response to the joint presence of thwarted belongingness and perceived burdensomeness. AIMS: To consider the potential influence of online interactions and behaviors on these outcomes. METHOD: To address this, we administered an online protocol assessing suicidal desire and online interactions in a sample of 305 undergraduates (83.6% female). We hypothesized negative interactions on social networking sites and a preference for online social interactions would be associated with thwarted belongingness. We also conducted an exploratory analysis examining the associations between Internet usage and perceived burdensomeness. RESULTS: Higher levels of negative interactions on social networking sites, but no other variables, significantly predicted thwarted belongingness. Our exploratory analysis showed that none of our predictors were associated with perceived burdensomeness after accounting for demographics, depression, and thwarted belongingness. CONCLUSION: Our findings indicate that a general tendency to have negative interactions on social networking sites could possibly impact suicidal desire and that these effects are significant above and beyond depression symptoms. Furthermore, no other aspect of problematic Internet use significantly predicted our outcomes in multivariate analyses, indicating that social networking in particular may have a robust effect on thwarted belongingness.

Hope and the interpersonal-psychological theory of suicidal behavior: replication and extension of prior findings.

The interpersonal-psychological theory of suicidal behavior (IPTS; Joiner, 2005) posits that suicidal behavior occurs when an individual has a desire for death (due to the combination of perceived burdensomeness and thwarted belongingness) in addition to an acquired capacity for suicide, which is present when the individual has a low fear of death and high pain tolerance. Previous research has demonstrated an expected negative relation between trait hope and perceived burdensomeness and thwarted belongingness, as well as a more perplexing finding that hope is positively associated with the acquired capability. In a sample of 230 college students, measures of the three components of the IPTS were administered, along with measures of hope, depression, and painful and/or provocative events. Hierarchical regression analyses replicated the previously found associations between hope and burdensomeness and belongingness while controlling for depression and demographic variables. The positive association between hope and acquired capacity was also replicated, but a mediation analysis demonstrated that the effect was statistically accounted for by distress tolerance. The results further support the incremental validity of hope as a consideration in suicide risk assessments and suggest that hope may serve as a protective factor with respect to suicidal desire.

Is there a role of targeted agents in the management of adrenocortical cancers?

Background. Adrenocortical carcinoma (ACC) is a rare and aggressive tumor arising from the adrenal cortex with an incidence of one to two cases per million within the general US population. Recent developments in the understanding of the pathogenesis of ACC have led to multiple clinical trials involving targeted agents in the management of ACC. Patients and Methods. We report two cases of refractory adrenocortical cancer (cisplatin, adriamycin, etoposide, and mitotane) who were treated with targeted agents such as erlotinib and sutent, respectively. A total of 2 women with adrenocortical cancer were reviewed and followed for a median time of 6 months. Radiological response, duration of response and toxicities were evaluated. Results. In both cases, the targeted agents were able to control the disease for a short duration, but due to the deterioration in performance status and fatigue the agents were discontinued. Conclusion. The current observations emphasize the need for better targeted treatment modalities and strategies for the management of this fatal disease.

'Off-label' drug use in sexual medicine treatment.

Phosphodiesterase type 5 inhibitors are the only drugs approved for a specific sexual function disorder. All other drugs used in the treatment of sexual disorders are used 'off-label.' This paper reviews the use of drugs in the treatment of premature ejaculation, Peyronie's disease and female hypoactive sexual desire disorder (HSDD). While the treatment of premature ejaculation is quite well documented and supported by evidence of good quality in the medical literature, there is little evidence for the use of the variety of medications in use for the treatment of Peyronie's disease. In particular, the use of verapamil is not supported by any double-blind studies whatsoever. The use of testosterone patch for treatment of HSDD in postmenopausal women is well documented, but not in premenopausal women.

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.