Cryptococcal meningitis is a life-threatening condition most commonly observed in immunocompromised individuals. We describe a daily cannabis smoker without evidence of immunodeficiency presenting ...with confirmed Cryptococcus neoformans meningitis. An investigation of cannabis samples from the patient’s preferred dispensary demonstrated contamination with several varieties of Cryptococcus, including C. neoformans, and other opportunistic fungi. These findings raise concern regarding the safety of dispensary-grade cannabis, even in immunocompetent users.
Objective: The purpose of this systematic review is to enumerate the psychiatric medications approved by the Food and Drug Administration (FDA) over the past 15 years, from 2008 to 2023, and describe ...their mechanism of action, approved indications, dosing ranges, and adverse effects. Methods: Studies published from 2008 to 2023 were identified from the PubMed database, using the keywords: ‘psychiatric’ OR ‘psychopharm*” AND ‘medic*’ OR ‘pharm*’. An independent focused analysis was conducted, and a consensus was reached on the studies for approved medications to be included in this systematic review. Key findings were derived from the full-text and tables of the selected studies. Results: From 2008-2023, the FDA approved 118 medications including: 26 for Schizophrenia, 12 for Bipolar Disorders, 16 for Depressive Disorders, two for Anxiety Disorders, one for Feeding and Eating disorders, 13 for Sleep-Wake Disorders, five for Sexual Dysfunctions, 16 for Substance Use Disorders, six for Neurocognitive Disorders, and 18 for Neurodevelopmental Disorders (specifically, Attention-Deficit/Hyperactivity Disorder, ADHD), in addition to three for Psychiatric Medication-Related Movement Disorders. It is important to note that 37 out of the 118 medications were New Drug Application (NDA) approvals by the FDA, i.e., they have not been previously approved for another indication. We also noted that nine medications were discontinued by the manufacturer, with no reported safety or effectiveness concerns. Over the past fifteen years, several novel treatment approaches and modalities have been introduced, such as monoclonal antibodies for the treatment of Alzheimer’s Disease, very long-acting injectable antipsychotic drugs, targeting the glutamate neurochemical system for depression and depressive symptoms in other disorders, medications for conditions without any previously approved medicines (e.g., Binge Eating Disorder), and tablets with sensors to monitor treatment adherence. Of note, no new medications were approved from 2008-2023 for: Anxiety Disorders (with the exception of two extended-release preparations of previously approved agents), Obsessive-Compulsive Disorder, Trauma- and Stressor-Related Disorders, Dissociation Disorders, Somatic Symptom Disorders, and Disruptive, Impulse-Control, and Conduct Disorders. Conclusion: Approved psychiatric medications from 2008-2023 show substantial promise in the treatment of psychiatric conditions. More than 100 psychiatric medications were approved over the past 15 years for the major psychiatric conditions including a combination of newly introduced medications and new indications and drug formulations for already approved medications. It behooves psychiatric clinicians to keep up to date with this ever evolving and fast changing field. As the overview article, this manuscript will be followed by in-depth, disorder-based descriptions of approved medications, as well as those currently under development in Phase III.
Objective/intervention: To compare the annual rates of acute otitis media (AOM) episodes, antibiotic days, and ventilating tube insertion during the first 3 years of life before and after a practice ...change to restrict use of antibiotic chemoprophylaxis for recurrent AOM.
Methods setting: The sole pediatric private practice in a rural Kentucky community.
Patients: Population-based sample of all children born consecutively in two different 13 month intervals. Cohort 1 (
n=251) was born before and Cohort 2 (
n=274) was born after restricted use of chemoprophylaxis and documented emergence of widespread penicillin non-susceptible
Streptococcus pneumoniae (PNSP).
Design: Retrospective case cohort comparison.
Main outcome measures: Suppurative AOM diagnosed by validated experienced otoscopists using stringent tympanic membrane criteria.
Results: Children were mostly white with the majority (50–65%) enrolled in daycare during each year. The first episode of AOM was experienced by 6 and 12 months of age in 64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2 were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3, respectively. Rates of new onset AOM and persistent AOM episodes were similar between cohorts in the first 2 years. Number of days of antibiotic prophylaxis were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2, and from 6.9 to 0.7 days in Year 3, respectively (
P<0.0001 for each year). Total antibiotic days for Years 1, 2 and 3 were reduced commensurately with prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days (
P=0.047), and from 38.7 to 25.7 days (
P<0.0001), respectively. For each year a non-significant trend for increased ventilating tube placement from Cohort 1 to Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8 versus 2.6%. Daycare attendance and white race were consistently significant risk factors for AOM and recurrent AOM.
Conclusions: in the era of PNSP, restricted use of antibiotic chemoprophylaxis for recurrent AOM was not associated with significantly increased rates of new onset AOM episodes or tube placement in the first 24 months of life. Total antibiotic days were also significantly reduced in Cohort 2 during Years 2 and 3.
To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS).
This is a retrospective cohort study using data from a single-center ...clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 and 2020 and prenatal brain magnetic resonance imaging (MRI) (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age (GA), as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated.
Compared with healthy controls, neonates with CDH had a significant delay in fTMS (P value <.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right vs left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation (ECMO), or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (P value = .025).
Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation.
To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both ...internal and external neutrons delivered via a Mevion single-room compact proton system.
Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent H* (10) were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth–dose data to in-air H* (10) values.
For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 106 to 1.04 × 107 n/cm2/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy.
For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines.
Objectives
Osteoarthritis (OA) is a common joint disease whose causes are not fully understood, but a longstanding hypothesis is that OA stems primarily from the cumulative effects of joint ...mechanical loading throughout life. Based on this wear and tear hypothesis, anthropologists have assumed that the presence of OA in archeological human skeletons can be interpreted as evidence of a highly physically active lifestyle. Here, we use guinea pigs to experimentally test the hypothesis that higher levels of routine physical activity result in greater OA degeneration.
Materials and methods
Guinea pigs are a useful model for OA research because they spontaneously develop the disease in a manner similar to humans. One group of growing animals was housed for 22 weeks in a large room that promoted voluntary physical activity (4.8 km of movement per day, on average), while animals in another group were housed in small cages that restricted their mobility (n = 15/group). After the experiment, histological and microcomputed tomographic analyses were conducted focusing on the knees.
Results
Rather than causing greater OA degeneration, elevated levels of routine physical activity resulted in significantly less knee cartilage deterioration, less synovial inflammation, smaller osteophytes, and maintenance of greater epiphyseal trabecular bone quantity.
Discussion
These results are inconsistent with the hypothesis that high levels of routine physical activity drive the pathogenesis of OA and call into question typical interpretations of OA in studies of archeological human skeletons.
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