A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome

Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary conclusion is supported by the evidence. Methods: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated. Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures. Conclusions: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed

Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive–compulsive disorder

In open trials, 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) improved symptoms and normalized cortical hyper-excitability of patients with obsessive–compulsive disorder (OCD). Here we present the results of a randomized sham-controlled double-blind study. Medication-resistant OCD patients (n=21) were assigned 4 wk either active or sham rTMS to the SMA bilaterally. rTMS parameters consisted of 1200 pulses/d, at 1 Hz and 100% of motor threshold (MT). Eighteen patients completed the study. Response to treatment was defined as a ≽25% decrease on the Yale–Brown Obsessive Compulsive Scale (YBOCS). Non-responders to sham and responders to active or sham rTMS were offered four additional weeks of open active rTMS. After 4 wk, the response rate in the completer sample was 67% (6/9) with active and 22% (2/9) with sham rTMS. At 4 wk, patients receiving active rTMS showed on average a 25% reduction in the YBOCS compared to a 12% reduction in those receiving sham. In those who received 8-wk active rTMS, OCD symptoms improved from 28.2±5.8 to 14.5±3.6. In patients randomized to active rTMS, MT measures on the right hemisphere increased significantly over time. At the end of 4-wk rTMS the abnormal hemispheric laterality found in the group randomized to active rTMS normalized. The results of the first randomized sham-controlled trial of SMA stimulation in the treatment of resistant OCD support further investigation into the potential therapeutic applications of rTMS in this disabling condition

WAIS-III and WMS-III performance in chronic Lyme disease

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects

Psychiatric Aspects of Lyme Disease in Children and Adolescents: A Community Epidemiologic Study in Westchester, New York

To date, no community study has examined the psychiatric aspects and or sequelae of Lyme disease (LO) among children. As part of a community epidemiologic study of psychiatric disorders among children ages 9 through 17 in a Lyme endemic county, parents were asked whether their child had ever been diagnosed as having LD, and 10.1% (36/357) responded yes to the LO question. Of the 36, 29 also agreed to take part in a follow-up interview. Sixteen of the 29 children had had physician-diagnosed LO as well as either an erythema migrans rash or a positive serology. Fifteen of these 16 received treatment within I month of symptom onset; none of these 15 children were symptomatic longer than 4 months. Only one child had physical symptoms at the time of the interview; she was not treated until 4 month~ after symptom onset. This child experienced 5 years of mtermittent arthritis, cognitive deficits, emotional problems, severe fatigue, and a deterioration in school performance. Courses of oral antibiotics were at first associated with a good response, followed by a resurgence of symptoms month<; later. The lifetime prevalence of LD by history among children ages 9 through 17 in an endemic area may be at least 44.8/1000. In general, when LD is diagnosed early, it responds well to treatment. Delayed diagnosis and treatment may lead to a chronic course

A Double-Masked, Placebo-Controlled Study of Fluoxetine for Hypochondriasis

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, T23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis

Directive 02-14: Tax Obligations of Persons Purchasing Cigarettes in Interstate Commerce for which the Massachusetts Cigarette Excise Has Not Been Paid

The development of accurate clinical biomarkers has been challenging in part due to the diversity between patients and diseases. One approach to account for the diversity is to use multiple markers to classify patients, based on the concept that each individual marker contributes information from its respective subclass of patients. Here we present a new strategy for developing biomarker panels that accounts for completely distinct patient subclasses. Marker State Space (MSS) defines "marker states" based on all possible patterns of high and low values among a panel of markers. Each marker state is defined as either a case state or a control state, and a sample is classified as case or control based on the state it occupies. MSS was used to define multi-marker panels that were robust in cross validation and training-set/test-set analyses and that yielded similar classification accuracy to several other classification algorithms. A three-marker panel for discriminating pancreatic cancer patients from control subjects revealed subclasses of patients based on distinct marker states. MSS provides a straightforward approach for modeling highly divergent subclasses of patients, which may be adaptable for diverse applications.</p

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

The Grizzly, April 15, 2004

Ursinus College Commencement Only One Month Away • Taking Our Place Campaign • Meet This Year\u27s Valedictorians • Silence Makes a Statement • Opinions: Make a Statement with Silence; Class of 2004 Campaigns Hard!; Hyped About Housing; Higher Gas Prices = Economical Cars • Faculty Spotlight: Houghton Kane • Chess Club Results • Who\u27s Who at Ursinus • Softball Team Continues to Shut Down Opponents • Ursinus Outdoor Track and Field: Experience for a Young Team • Baseball Team Trying to be a Contender • Grimmel, Furman Earn All-American Honors at NCGA Championships • Durkin Named CC Player of the Weekhttps://digitalcommons.ursinus.edu/grizzlynews/1559/thumbnail.jp

Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy

Context: There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease. Objectives: To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR). Design: Case-controlled study. Setting: A university medical center. Participants: A total of 35 patients and 17 healthy volunteers (controls). Patients had well-documented prior Lyme disease, a currently reactive IgG Western blot, prior treatment with at least 3 weeks of intravenous cephalosporin, and objective memory impairment. Main Outcome Measures: Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia). Results: Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (P < .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements. Conclusions: Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease

Effects of Lockdown Restrictions and Impact of Anxiety and Depression Symptoms in People With Chronic Pain During the Covid-19 Pandemic: A 13-wave Longitudinal Study

In early 2020, countries across the world imposed lockdown restrictions to curb the spread of the Covid-19 coronavirus. Lockdown conditions, including social and physical distancing measures and recommended self-isolation for clinically vulnerable groups, were proposed to disproportionately affect those living with chronic pain, who already report reduced access to social support and increased isolation. Yet, empirical evidence from longitudinal studies tracking the effects of prolonged and fluctuating lockdown conditions, and potential psychological factors mediating the effects of such restrictions on outcomes in chronic pain populations, is lacking. Accordingly, in the present 13-wave longitudinal study, we surveyed pain intensity, pain interference, and tiredness in people with chronic pain over the course of 11 months of the Covid-19 pandemic (April 2020–March 2021). Of N = 431 participants at baseline, average completion rate was ∼50% of time points, and all available data points were included in linear mixed models. We examined the impact of varying levels of lockdown restrictions on these outcomes and investigated whether psychological distress levels mediated effects. We found that a full national lockdown was related to greater pain intensity, and these effects were partially mediated by depressive symptoms. No effects of lockdown level were found for pain interference and tiredness, which were instead predicted by higher levels of depression, anxiety, pain catastrophising, and reduced exercise. Our findings are relevant for improving patient care in current and future crises. Offering remote management options for low mood could be particularly beneficial for this vulnerable population in the event of future implementation of lockdown restrictions