Provision of COVID-19 Convalescent Plasma in a Resource-Constrained State.

BACKGROUND: Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. The first case of coronavirus disease 2019 (COVID-19) in Arkansas occurred on 11 March 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID-19 convalescent plasma (CCP) was explored as a potentially lifesaving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. STUDY DESIGN AND METHOD: This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that CCP was available in a resource-limited state. RESULTS: Early contact tracing by ADH identified individuals who had come into contact with "patient zero" in early March. Within the first week, 32 patients tested positive for COVID-19. The first set of CCP collections occurred on 9 April 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. CONCLUSIONS: The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource-limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials.

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.

Transcranial magnetic stimulation in the treatment of chronic widespread pain: a randomized controlled study.

OBJECTIVE: Our objective was to assess transcranial magnetic stimulation (TMS) in the treatment of chronic widespread pain. METHODS: Nineteen participants were randomized into 2 groups: one group receiving active TMS (n = 7) and another group receiving sham stimulation (n = 11) applied to the left dorsolateral prefrontal cortex. During sham stimulation, subjects heard a sound similar to the sound heard by those receiving the active treatment and received an active electrical stimulus to the scalp. The stimulation protocol consisted of 15 sessions completed within a 4-week period. Blind assessments were done at baseline and after each 5 sessions followed by blind assessments at 1 week, 1 month, and 3 months after the last TMS sessions. The primary outcome variable was a pain measure, the Gracely Box Intensity Scale (BIRS). RESULTS: The percentage of subjects who guessed that they were receiving TMS was similar in the 2 groups. Both the TMS group and the sham group showed a statistically significant reduction in the BIRS scores from baseline during the acute phase of treatment and the follow-up phase. However, the TMS and sham groups did not differ in the change in the BIRS scores. DISCUSSION: Although some previous clinical studies and basic science studies of TMS in treating pain are promising, this study found no difference in the analgesic effect of TMS and sham stimulation. Future studies should use a sham condition that attempts to simulate the sound and sensation of the TMS stimulation. Stimulus location and other stimulus parameters should be explored in future studies.

No change in neuropsychological functioning after receiving repetitive transcranial magnetic stimulation treatment for major depression.

Early studies of transcranial magnetic stimulation (TMS) have shown no adverse effects on neuropsychological function. However, further research using higher TMS intensities as well as a greater number of TMS pulses and with larger sample sizes is needed. We studied 68 patients with major depressive disorder who were randomized to receive either 15 sessions of sham or real TMS at 110% of the estimated prefrontal cortex threshold to the left dorsolateral prefrontal cortex. Each session consisted of 32 5-second trains of 10-Hz repetitive TMS at 110% adjusted motor threshold. A total of 24,000 pulses were given. Neuropsychological function was assessed before and immediately after TMS treatment with a battery of 8 tests. Using a higher TMS intensity as well as a greater number of pulses and having a larger sample size compared with most previous studies, this study found no negative neuropsychological effects of TMS. Changes in neuropsychological function were unrelated to changes in depression.

Grazers modify the dinoflagellate relationship between toxin production and cell growth.

Although the typical framework for studies and models of bloom dynamics in toxigenic phytoplankton is predominantly based on abiotic determinants, there is mounting evidence of grazer control of toxin production. We tested for the effect of grazer control of toxin production and cell growth rate during a laboratory-simulated bloom of the dinoflagellate Alexandrium catenella. We measured cellular toxin content and net growth rate when cells were exposed to copepod grazers (direct exposure), copepod cues (indirect exposure), and no copepods (control) throughout the exponential, stationary, and declining phases of the bloom. During the simulated bloom, cellular toxin content plateaued after the stationary phase and there was a significantly positive relationship between growth rate and toxin production, predominantly in the exponential phase. Grazer-induced toxin production was evident throughout the bloom, but highest during the exponential phase. Induction was greater when cells were directly exposed to grazers rather than their cues alone. In the presence of grazers toxin production and cell growth rate were negatively related, indicating a defense-growth trade-off. Further, a fitness reduction associated with toxin production was more evident in the presence than the absence of grazers. Consequently, the relationship between toxin production and cell growth is fundamentally different between constitutive and inducible defense. This suggests that understanding and predicting bloom dynamics requires considering both constitutive and grazer-induced toxin production.

Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression.

BACKGROUND: A few studies have examined the durability of transcranial magnetic stimulation (TMS) antidepressant benefit once patients remitted. This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up. METHODS: Patients were remitters from an acute double-blind sham-controlled trial of TMS (n = 18), or from an open-label extension in patients who did not respond to the acute trial (n = 43). Long-term durability of TMS acute effect was examined in remitters over a 12-week follow-up. Relapse, defined as 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20, was the primary outcome. RESULTS: Of 61 remitters in the acute trial, five entered naturalistic follow-up and 50 entered the TMS taper. Thirty-two patients completed TMS taper and 1-, 2-, and 3-month follow-up. At 3-month visit, 29 of 50 (58%) were classified as in remission (HDRS-24 ≤10), two of 50 (4%) as partial responders (30%≤ HDRS-24 reduction <50% from baseline), and one of 50 (2%) met criteria for relapse. During the entire 3-month follow-up, five of the 37 patients relapsed (relapse rate = 13.5%), but four of them regained remission by the end of the study. The average time to relapse in these five patients was 7.2 ± 3.3 weeks. Patients who relapsed had higher depression scores at 1 month. CONCLUSIONS: While one third of the sample was lost to follow-up, our results demonstrate that most patients contributing to observations experienced persistence of benefit from TMS followed by pharmacotherapy or no medication. Longer follow-up and more rigorous studies are needed to explore the true long-term durability of remission produced by TMS.

Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression.

OBJECTIVE: To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment-resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC). METHOD: Patients were part of a multicenter sham-controlled trial investigating the efficacy of fast left rTMS. Patients who failed to meet minimal response criteria in the sham-controlled study could enroll in this open fast left rTMS study for an additional 3-6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to 4 additional weeks. The final outcome measure was remission, defined as a HAM-D score of <3 or 2 consecutive HAM-D scores less than 10. RESULTS: Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). Twenty-six percent of patients who failed fast left remitted during slow right treatment. CONCLUSION: The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations.

Evidence-based guidelines for the care and maintenance of complete dentures: a publication of the American College of Prosthodontists.

The current rates of edentulism have been estimated to be between 7% and 69% of the adult population internationally. In the United States, while the incidence of edentulism continues to decline, rapid population growth coupled with current economic conditions suggest that edentulism and conventional denture use will continue at current or higher numbers. Unfortunately, evidence-based guidelines for the care and maintenance of removable complete denture prostheses do not exist. In 2009, the American College of Prosthodontists (ACP) formed a task force to establish evidence-based guidelines for the care and maintenance of complete dentures. The task force comprised members of the ACP, the Academy of General Dentistry, American Dental Association (ADA) Council on Scientific Affairs, the American Dental Hygienists' Association, the National Association of Dental Laboratories, and representatives from GlaxoSmithKline Consumer Healthcare. The review process included the assessment of over 300 abstracts and selection of over 100 articles meeting inclusion criteria of this review. The task force reviewed synopses of the literature and formulated 15 evidence-based guidelines for denture care and maintenance. These guidelines were reviewed by clinical experts from the participating organizations and were published in February 2011 issue of The Journal of the American Dental Association for widespread distribution to the dental community. These guidelines reflect the views of the task force.

Hemispheric asymmetry in resting motor threshold in major depression.

OBJECTIVES: Previous studies of repetitive transcranial magnetic stimulation suggest a hemispheric imbalance in patients with major depression. These studies report an antidepressant effect by activation of the left prefrontal cortex or inhibition of the right prefrontal cortex. The aim of this study is to investigate interhemispheric differences in cortical excitability in a large sample of patients with major depression. METHODS: The resting motor threshold (RMT) was measured on 91 patients with treatment-resistant major depression. We controlled for current medication use, gender, age, handedness, and study site. RESULTS: There was no significant difference between the left RMT (55.96 [10.356]) and the right (57.74 [11.359]) (P = 0.131, Wilcoxon matched-pairs test). A multivariate analysis found no significant association between depression scores and right or left RMT. After adjusting for important cofactors, benzodiazepine use was found to be a significant predictor of left RMT (P = 0.017, linear regression) and right RMT (P = 0.007, linear regression). CONCLUSION: Our results do not support the existence of an interhemispheric imbalance of cortical excitability in depressed patients. Benzodiazepine use was found to raise both the left and right RMT.

Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism.

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.

Hotel Room Suicide: Cuyahoga, Orange, Travis, and Wayne Counties.

OBJECTIVE: To compare the suicide rates of local residents registering in local hotels with the general suicide rate in that county and to compare the suicide rates of hotel guests from outside the county with the national suicide rate. METHODS: The numbers of cases of suicide in hotel rooms and the general community were tabulated for Cuyahoga County, Ohio, for calendar years 2010-2017; in Orange County, California, and Travis County, Texas, for 2010-2012; and in Wayne County, Michigan, for 1997 to March 2005. The percentage of local residents registering in local hotel rooms was estimated from various sources to stratify the suicide risk for travelers and local residents. RESULTS: The suicide rate of local residents registering in local hotels was elevated compared to the general nonhotel population in each county (range of relative risk, 15.1-37.8; P < .0001, Poisson distribution). Hotel guests from outside each county had a reduced rate of suicide compared to the national rate (range of relative risk, 0.124-0.524; P < .05, Poisson distribution). With regard to suicide method, drug overdoses accounted for a significantly greater percentage in hotel rooms than in the nonhotel population in 3 of 4 counties (range of risk ratios, 2.03-4.51, P < .01; test of proportions), with the opposite pattern for gunshot wounds (range of risk ratios, 0.27-0.50; P < .01, test of proportions). CONCLUSIONS: Although local residents register in hotels for various reasons, there appears to be a subpopulation with a purpose of avoiding rescue. Consistent with the risk-rescue rating, means of suicide with lower lethality, eg, drug overdoses, account for a greater percentage of cases in a setting with less chance of rescue. In contrast to the local use population, the sense of purpose or meaning inherent in travel could explain the decreased risk of suicide in guests from outside the county.

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment for depression has shown statistically significant effects, but the clinical significance of these effects has been questioned. METHODS: Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110% the estimated prefrontal cortex threshold. Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end point was treatment response defined as a >or=50% decrease in Hamilton Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS: The response rate for the TMS group was 30.6% (11/35), significantly (p = .008) greater than the 6.1% (2/33) rate in the sham group. The remission rate for the TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33) rate in the sham group. The HDRS scores showed a significantly (p < .002) greater decrease over time in the TMS group compared with the sham group. CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and clinically significant antidepressant effects in patients with medication-resistant major depression.

Hotel room suicide.

The objective of our research was to quantify the increased risk of suicide associated with registering in local hotels/motels. Medical examiner case files of suicide in King County, Washington, were reviewed for years 2002-2004. The incidence of suicide in local residents registering in local hotels/motels was 223/100,000 which is significantly greater than the incidence of suicide in the general population of King County (11.7/100,000 p < 0.0001). Hotel/motel guests from outside Washington had a significantly reduced incidence of suicide (3.9/100,000 p = 0.002). The study results suggest that there is an increased risk of suicide in local residents who register in local hotel rooms.

Comparison of apexification with mineral trioxide aggregate and calcium hydroxide.

PURPOSE: The aim of this study was to compare mineral trioxide aggregate (MTA) with calcium hydroxide [Ca(OH)2] clinically and radiographically as materials used to induce root-end closure in necrotic permanent teeth with immature apices (apexification). METHODS: Fifteen children, each with at least 2 necrotic permanent teeth requiring root-end closure (apexification), were selected for this study. All selected teeth were evenly divided into 2 test groups. In group 1, the conventional calcium hydroxide apexification (control) was performed, whereas in group 2, the MTA apexification (experimental) was done. The children were recalled for clinical and radiographic evaluations after 3, 6, and 12 months. RESULTS: The follow-up evaluations revealed failure due to persistent periradicular inflammation and tenderness to percussion detected at 6 and 12 months postoperative evaluation in only 2 teeth treated with Ca(OH)2. The remaining 13 teeth appeared to be clinically and radiographically successful 12 months postoperatively. None of the MTA-treated teeth showed any clinical or radiographic pathology. CONCLUSIONS: Mineral trioxide aggregate showed clinical and radiographic success as a material used to induce root-end closure and is a suitable replacement for calcium hydroxide for the apexification procedure.