A Real-World Study on Myopia Control 6 Months After Withdrawal of 1% Atropine Eye Gel

Purpose: This study aimed to observe the changes in spherical equivalent and ocular axial length 6 months after withdrawal of 1% atropine eye gel.Methods: Due to COVID-19, the follow-up of patients in our optometric clinic who were undergoing myopia control treatment with a dropwise 1% atropine “5+3” regimen was interrupted. No return visit was made after the 3 months of at-home treatment, and follow-ups resumed 6 months after treatment withdrawal. The contralateral eye was not treated over the 9-month period. A total of 16 patients aged 11.5 years (average) were enrolled from November 2019 to March 2021 during the COVID-19 pandemic. The treated eyes formed a treatment group (16 eyes) and the contralateral eyes formed a control group (16 eyes). The changes in spherical equivalent, ocular axial length, and intraocular pressure (IOP) were compared between groups. Results: After 9 months, the changes in spherical equivalent were significantly less in the treatment group (0.00 ± 0.20 [D]) compared to the control group (-0.67 ± 0.25 [D]) (P<0.05). The ocular axial length changes were significantly less in the treatment group (0.00 ± 0.06 mm) compared to the control group (0.25 ± 0.11 mm) (P<0.05). There was no significant difference between the two groups for changes in IOP. Conclusions: Despite treatment withdrawal after 3 months, treatment with 1% atropine eye gel successfully controlled myopia progression in the 6 months after withdrawal, as evidence by no rebound increase in myopic spherical equivalent after the withdrawal.

Reduction of free-roaming cat population requires high-intensity neutering in spatial contiguity to mitigate compensatory effects

When free-roaming in natural areas, the domestic cat (Felis silvestris catus) is ranked high among the most destructive alien species. Near human vacancy, it might risk humans, impair sanitation, and suffer from poor welfare. Cats’ popularity as companion animals complicates their population control. Thus, culling is often replaced by a fertility control method called “Trap-Neuter-Return/Release (TNR),” which is considered more humane. Despite the extensive application of TNR, a long-term controlled study was never performed to test its effectiveness. We present a uniquely designed controlled field experiment for examining TNR effectiveness. The study was performed over a twelve-year period, divided into pre-intervention, mixed- and full-intervention phases, and spanned a 20Km2 urban area. Trends of cat, queen, and kitten counts, cat reproduction, and carcass reports were compared among study phases and areas with different neutering intensities. The cat population increased during the first two study phases and did not decline in highly neutered populations, presumably due to cat immigration. Expansion of high-intensity neutering to the entire city in the full-intervention phase (>70% neutering percentage) reversed cat population growth, reaching an annual ca. 7% reduction. This population reduction was limited by a rebound increase in cat reproduction and longevity. We conclude that cat population management by TNR should be performed in high-intensity, continuously, and in geographic contiguity to enable population reduction. To enhance management effectiveness and mitigate compensatory effects, we recommend further evaluating an integrated strategy that combines TNR with complementary methods (e.g., vital resource regulation, ill cat euthanasia, and adoption).Significance StatementThough popular companion animals, domestic cats pose numerous problems when free-roaming, including predation of wildlife, hazards to humans, impaired sanitation, and a decrease in their welfare. Thus, managing their populations is essential. The Trap-Neuter-Return method (TNR, capturing, sterilizing, returning/releasing) is widely employed for managing cat populations. However, its use is under continuous debate due to the lack of long-term controlled evidence. We examined the outcomes of high-intensity TNR by performing a twelve-year controlled field experiment, the largest to date. Neutering over 70% of the cats caused population decline when applied over contiguous areas. However, it was limited by a rebound increase in reproduction and survival. These findings provide a robust quantification of the limitations and the long-term effectiveness of TNR.

Mannitol is comparable to hypertonic saline for raised intracranial pressure in Acute Liver Failure (MAHAL Study): A RCT

Background: Raised intracranial pressure due to cerebral edema (CE) is central to development of hepatic encephalopathy in ALF. Mannitol (MT) & Hypertonic saline (HS) has been shown to improve CE. We compared the efficacy & safety of the two modalities Methods: ALF with CE were prospectively randomized in an open study to receive either 5 ml/kg of either 3% HS, as continuous infusion; titrated every 6 hourly to achieve serum sodium of <160(Group A; n=26) or 1 g/kg of 20% MN as a IV bolus, repeated every six hourly (Group B; n=25) in addition to standard ALF care. Primary end-point was reduction of intracranial pressure defined as optic nerve sheath diameter <5mm and middle cerebral arterial pulsatility index (PI) <1.2 at 12 hours. Results: Fifty-one patients with ALF, hepatitis E being commonest (33.3%), median jaundice to HE interval of 8(1-16) days, were randomized to HS (n=26) or MN (n=25). Baseline characteristics were comparable including King’s college criteria [>2: 38.4% vs.40%]. Overall, 61.5% patients in HS and 56% in MN group showed reduction in ICP at 12 hr. (p=0.25). Rebound increase in ICP indices was noted in 5(20%) patients in MT and none in HS (p<0.05) group. New onset acute kidney injury was commoner in MT than HS group. The ICU stay, and 28-day transplant free survival were not different between the groups. Conclusions: While both agents had comparable efficacy in reducing ICP and mortality in ALF patients was comparable, HS was significantly better in preventing reducing rebound CE with lower renal dysfunction.

Mandatory Prescription Limits and Opioid Use After Anterior Cruciate Ligament Reconstruction

Background: Because of the need for perioperative pain management, orthopaedic surgeons play an important role in opioid use. Purpose/Hypothesis: To evaluate the impact of opioid-limiting legislation on postoperative opioid use and pain-related complications after anterior cruciate ligament reconstruction (ACLR). The hypothesis was that the opioid-limiting legislation would reduce postoperative opioid use after ACLR. Study Design: Cohort study; level of evidence, 3. Methods: We retrospectively reviewed patients who underwent ACLR 1 year before and 1 year after Ohio's opioid-limiting legislation, which was passed in August 2017. Clinicians were prohibited from prescribing more than 30 morphine milligram equivalents (MMEs) per day, with a maximum duration of 7 days for adults. The Ohio Automated Rx Reporting System database and patients’ medical charts were reviewed for prescriptions of all controlled substances (oral oxycodone, hydrocodone, morphine, codeine, tramadol, and hydromorphone) filled from 30 days before and 90 days after ACLR. The total number of postoperative prescriptions, total MMEs, the number of pills in each patient’s prescription, and pain-related complications (emergency department visits, office calls for pain control issues, unplanned readmissions, unplanned surgeries, and provider notes indicating opioid prescription refill demands) were evaluated. Results: A total of 243 patients (127 prelegislation, 116 postlegislation) were included in the study. There were no significant differences in demographics or preoperative opioid use between the study groups. The number of pills prescribed initially decreased by 34% after legislation (63.5 ± 16.7 [prelegislation] vs 42 ± 15.7 pills [postlegislation]; P < .001). Correspondingly, there was a significant decrease in total quantity of initial prescriptions in the postlegislation period (474.6 ± 123.8 vs 310.7 ± 115.3 MMEs; P < .001). The number of documented pain medication refill demands and pain-related complications did not increase in the postlegislation period (42 prelegislation vs 43 postlegislation; P = .514). Preoperative opioid use was the strongest predictor of opioid-refill demand (odds ratio, 4.19 [95% CI, 1.76-9.99]; P = .001). Conclusion: After the Ohio legislation was passed limiting opioid prescription, there was a significant reduction in opioids provided for patients undergoing ACLR. In spite of this decrease, no rebound increase in refill demands or postoperative pain-related complications were observed.

Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients

Background Procalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections. Methods In this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D−T−), dexamethasone, no tocilizumab (D+T−), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T− and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection. Results Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T− group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T− group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively). Conclusions Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.

Properties of multi-vesicular release from mouse rod photoreceptors support transmission of single photon responses

Vision under starlight requires rod photoreceptors transduce and transmit single photon responses to the visual system. Small single photon voltage changes must therefore cause detectable reductions in glutamate release. We found that rods achieve this by employing mechanisms that enhance release regularity and its sensitivity to small voltage changes. At the resting membrane potential in darkness, mouse rods exhibit coordinated and regularly timed multivesicular release events, each consisting of ~17 vesicles and occurring 2-3 times more regularly than predicted by Poisson statistics. Hyperpolarizing rods to mimic the voltage change produced by a single photon abruptly reduced the probability of multivesicular release nearly to zero with a rebound increase at stimulus offset. Simulations of these release dynamics indicate that this regularly timed, multivesicular release promotes transmission of single photon responses to post-synaptic rod bipolar cells. Furthermore, the mechanism is efficient, requiring lower overall release rates than uniquantal release governed by Poisson statistics.

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder

Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.

Maxillofacial Trauma and COVID-19: A Review of the First 6 Months of the Pandemic

Study Design: Retrospective cohort study. Objective: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in late December 2019 has spread globally resulting in a pandemic of respiratory illness. The purpose of this study is to understand the impact of the first 6 months of the COVID-19 pandemic on the epidemiology of maxillofacial trauma at an urban trauma center. Methods: The study sample was derived from the population of patients who presented for evaluation and management of maxillofacial injuries at TriStar Skyline Medical Center in Nashville, Tennessee beginning March 1, 2020 and ending August 31, 2020, compared to the same period in 2019. Descriptive and bivariate statistics were calculated for study variables in each cohort with significance set at P < .05. Results: The number of subjects in the 2020 cohort (n = 212) was 4.2% higher than the 2019 cohort (n = 203). Volume decreased 24.5% during the initial phase of the pandemic with a 36.1% increase in volume occurring during the reopening phase (P = .003). Volume related to interpersonal decreased 52.4% during the initial phase of the pandemic with a rebound increase of 30% during reopening (P = .005). Conclusion: The first case of COVID-19 presented in Nashville, Tennessee in early March 2020. Over the next 6 months, periods of lockdown and reopening transpired. The volume of maxillofacial trauma decreased during the initial 3-months of the pandemic and rebounded to volumes greater than the year prior.

Current Challenges in Osteoporosis Treatment Discontinuation

Osteoporosis is a chronic disease that may require lifelong therapy. Therefore, evidence-based approach regarding the efficacy and safety of long‐term osteoporosis therapy and therapy discontinuation is important. The most important goals for osteoporosis and fragility fracture patients are the recovery of pre-fracture functional level and reduction of fracture risk. There has been increasing consensus that a treat-to-target (T2T) strategy is applicable to osteoporosis and that bone mineral density (BMD) is currently the most clinically appropriate target. However, there is no clear consensus with regard to the definition of a specific BMD treatment target and timeframes applicable to T2T in osteoporosis, and these would need to be individually determined. Treatment with bisphosphonates may be interrupted after 3-5 years, only in patients in whom fracture risk is low or lowered because of the treatment itself. It is recommended never to discontinue treatment in patients with one or more prevalent osteoporotic fractures or in whom the BMD values are still below -2.5 (T score). Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures. Patients considered at high fracture risk should either continue denosumab therapy for up to ten years or be switched to an alternative treatment. For patients at low-risk, a decision to discontinue denosumab could be made after five years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover.

Properties of multi-vesicular release from rod photoreceptors support transmission of single photon responses

Vision under starlight requires rod photoreceptors to transduce and transmit single photon responses to the visual system. This remarkable sensitivity depends on a small voltage change reliably reducing glutamate release such that post-synaptic rod bipolar cells can robustly detect the signal. To transmit this small signal, we have found that rod vesicle release deviates strongly from a Poisson process under conditions that mimic darkness. Specifically, at their resting membrane potential in darkness, rods exhibit coordinated and regularly timed multivesicular release events. Each release event consisted of ∼17 vesicles and occurred 2-3 times more regularly than expected from a Poisson process. Hyperpolarizing rods to mimic the voltage change produced by a single photon response abruptly reduced the probability of multivesicular release nearly to zero with a rebound increase in release probability at stimulus offset. Simulations of these release dynamics indicate that this regularly timed, multivesicular release promotes transmission of single photon responses to post-synaptic neurons. Furthermore, the mechanism is efficient, requiring fewer vesicles to be released per second than uniquantal release governed by Poisson statistics.