Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

Chronic Subdural Hematoma (CSDH) is a common hemorrhagic disease in neurosurgery, and with the intensification of global aging, its incidence is gradually increasing. With the advancement of scientific technology, the etiological concepts and surgical treatments for CSDH have continually evolved over time. Currently, neuroscientists\' understanding of CSDH is no longer confined to bridging vein rupture; exploration of various mechanisms such as angiogenesis, maturation of blood vessels, and inflammation is also underway. In-depth exploration and discovery of pathogenic mechanisms guide the updating of clinical treatment strategies and methods. For different types of CSDH, there is now a clear guidance for the targeted selection of treatment methods. However, the current treatment of CSDH cannot completely solve all problems, and the updating of treatment methods as well as the development and validation of new effective drugs remain challenges for the future. In addition, the recurrence of CSDH is a significant issue that needs to be addressed. Although we have reviewed potential recurrent factors that may be associated, the strength of this evidence is insufficient. Future research should gradually focus on validating these recurrent factors and exploring new ones, in order to optimize the existing understanding and treatment of CSDH.

BACKGROUND: Punitive legal responses to prenatal drug use may be associated with unintended adverse health consequences. However, in a rapidly shifting policy climate, current information has not been summarized. We conducted a survey of U.S. state policies that utilize criminal or civil legal system penalties to address prenatal drug use. We then systematically identified empirical studies evaluating these policies and summarized their potential public health impacts.
METHODS: Using existing databases and original statutory research, we surveyed current U.S. state-level prenatal drug use policies authorizing explicit criminalization, involuntary commitment, civil child abuse substantiation, and parental rights termination. Next, we systematically identified quantitative associations between these policies and health outcomes, restricting to U.S.-based peer-reviewed research, published January 2000-December 2022. Results described study characteristics and synthesized the evidence on health-related harms and benefits associated with punitive policies. Validity threats were described narratively.
RESULTS: By 2022, two states had adopted policies explicitly authorizing criminal prosecution, and five states allowed pregnancy-specific and drug use-related involuntary civil commitment. Prenatal drug use was grounds for substantiating civil child abuse and terminating parental rights in 22 and five states, respectively. Of the 16 review-identified articles, most evaluated associations between punitive policies generally (k = 12), or civil child abuse policies specifically (k = 2), and multiple outcomes, including drug treatment utilization (k = 6), maltreatment reporting and foster care entry (k = 5), neonatal drug withdrawal syndrome (NDWS, k = 4) and other pregnancy and birth-related outcomes (k = 3). Most included studies reported null associations or suggested increases in adverse outcome following punitive policy adoption.
CONCLUSIONS: Nearly half of U.S. states have adopted policies that respond to prenatal drug use with legal system penalties. While additional research is needed to clarify whether such approaches engender overt health harms, current evidence indicates that punitive policies are not associated with public health benefits, and therefore constitute ineffective policy.

Tweetable abstract Update on the genetic variants with the highest level of Pharmacogenomics Knowledge Base evidence for their association with toxicity and efficacy in response to the most commonly used disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis.

The emergence and persistence of drug-resistant tuberculosis is a major threat to global public health. Our objective was to assess the applicability of whole-genome sequencing (WGS) to detect genomic markers of drug resistance and explore their association with treatment outcomes for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB).
METHODS: Five electronic databases were searched for studies published in English from the year 2000 onward. Two reviewers independently conducted the article screening, relevant data extraction, and quality assessment. The data of the included studies were synthesized with a narrative method and are presented in a tabular format.
RESULTS: The database search identified 949 published articles and 8 studies were included. An unfavorable treatment outcome was reported for 26.6% (488/1834) of TB cases, which ranged from 9.7 to 51.3%. Death was reported in 10.5% (194/1834) of total cases. High-level fluoroquinolone resistance (due to gyrA 94AAC and 94GGC mutations) was correlated as the cause of unfavorable treatment outcomes and reported in three studies. Other drug resistance mutations, like kanamycin high-level resistance mutations (rrs 1401G), rpoB Ile491Phe, and ethA mutations, conferring prothionamide resistance were also reported. The secondary findings from this systematic review involved laboratory aspects of WGS, including correlations with phenotypic DST, cost, and turnaround time, or the impact of WGS results on public health actions, such as determining transmission events within outbreaks.
CONCLUSIONS: WGS has a significant capacity to provide accurate and comprehensive drug resistance data for MDR/XDR-TB, which can inform personalized drug therapy to optimize treatment outcomes.

Expanding access to medications to treat opioid use disorder (OUD), such as buprenorphine, is an evidence-based response to the mounting drug overdose crisis. However, concerns about buprenorphine diversion persist and contribute to limited access.
To inform decisions about expanding access, a scoping review was conducted on publications describing the scope of, motivations for, and outcomes associated with diverted buprenorphine in the U.S.
In the 57 included studies, definitions for diversion were inconsistent. Most studied use of illicitly-obtained buprenorphine. Across studies, the scope of buprenorphine diversion ranged from 0% to 100%, varying by sample type and recall period. Among samples of people receiving buprenorphine for OUD treatment, diversion peaked at 4.8%. Motivations for using diverted buprenorphine were self-treatment, management of drug use, to get high, and when drug of choice was unavailable. Associated outcomes examined trended toward positive or neutral, including improved attitudes toward and retention in MOUD.
Despite inconsistent definitions of diversion, studies reported a low scope of diversion among people receiving MOUD, with inability to access treatment as a motivating factor for using diverted buprenorphine, and increased retention in MOUD as an outcome associated with use of diverted buprenorphine. Future research should explore reasons for diverted buprenorphine use in the context of expanded treatment availability to address persistent barriers to evidence-based treatment for OUD.

UNASSIGNED: To systematically evaluate the effectiveness of exposure and response prevention (ERP) combined with medication on obsessive-compulsive disorder (OCD).
UNASSIGNED: PubMed, Web of Science, EBSCO, Cochrane, Embase, and Science Direct databases were searched to include randomized controlled trials of ERP combined with medication for OCD that met the criteria. The Yale Brown Obsessive Compulsive Scale was used as the primary outcome indicator, and Depression scales were used as secondary outcome indicators. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. Review Manager 5.3 and Stata 16.0 software was used to perform meta-analysis of the extracted data.
UNASSIGNED: A total of 21 studies with 1113 patients were included. Meta-analysis showed that ERP combined with medication therapy was significantly better than medication therapy alone including selective serotonin reuptake inhibitors, clomipramine and risperidone (MD = -6.60, 95% CI: -8.35 to -4.84, P < 0.00001), but D-cycloserine (DCS) drugs do not enhance the effect of ERP intervention in patients with OCD (MD = 0.15, 95% CI: -0.87 to 1.17, P = 0.77). There is more significant maintenance by combined treatment method of medication plus ERP than medication treatment alone during the follow-up period (MD = -7.14, 95% CI: -9.17 to -5.10, P < 0.00001). DCS drugs did not enhance the effect of ERP intervention on depression in patients with OCD (SMD = -0.08, 95% CI: -0.31 to 0.15, P = 0.50). ERP combined with drug improved patients\' depression levels significantly better than providing drug alone (SMD = -0.40, 95% CI: -0.68 to -0.11, P = 0.006).
UNASSIGNED: Patients with OCD have significant improvement in symptoms of obsessive-compulsive disorder and depression when ERP is combined with medication, however, not enough to prove that DCS can enhance ERP effectiveness.

BACKGROUND: Petrositis is a rare and fatal complication associated with otitis media. It is most likely caused by bacterial infections, but in some cases it is caused by fungal infections.
METHODS: The case in this report is associated with fungal petrositis. The clinical symptoms are: ear pain from chronic otitis media, severe headache, peripheral facial palsy and diplopia. The case was finally confirmed through imaging of middle ear, bacterial culture, pathology, and blood Metagenomic next-generation sequencing (mNGS) test. The patient was treated with sensitive antifungal drugs.
CONCLUSIONS: Drug treatment is conservative but efficient method in this case. mNGS can provide pathogenic reference, when antibiotic is not efficient enough for fungal infections or drug-resistant fungal infections cases. This allows we to adjust drug use for the treatment.

UNASSIGNED: Although obsessive-compulsive personality disorder (OCPD) is one of the most prevalent personality disorders, it is one of the least studied. There is debate as to whether pharmacotherapy is efficacious for OCPD. We aimed to systematically evaluate the efficacy and tolerability of pharmacotherapy for OCPD.
UNASSIGNED: This systematic review found two randomized controlled trials investigating pharmacotherapy of OCPD. In a study of major depression (n = 308) with comorbid OCPD (n = 71), citalopram was more effective for OCPD than sertraline with fewer drop-outs from treatment. In a small study of OCPD (n = 24), fluvoxamine was more effective than placebo, and there was a low drop-out rate. Risk of bias and quality assessment of these studies was not possible, and findings have very low levels of certainty.
UNASSIGNED: Two studies provide preliminary evidence in support of citalopram and fluvoxamine for OCPD. Further randomized controlled trials are required before firm conclusions can be drawn regarding efficacy of pharmacotherapy for OCPD.

Depressive symptom is the prevailing non-motor symptom of Parkinson\'s disease (PD). Drug treatments for depressed PD (dPD) can mitigate the symptoms of patients. However, the results are discordant and need further analysis. This systematic review with network meta-analysis aims to evaluate the drug treatments for dPD. We included double-blind, randomized controlled trials to compare antidepressants with placebo or other antidepressants in dPD. We performed traditional pairwise analysis and network meta-analysis concerning the efficacy, acceptability, depression score, and adverse effect. The surface under the cumulative ranking curve was to assess the ranking probabilities of the enrolled agents. We enrolled 62 studies, including 12,353 subjects, to analyze these estimates. For the traditional pairwise meta-analysis, dopamine agonist (DOP; OR = 2.20 [95% CI, 1.46 to 3.33]) and selective serotonin reuptake inhibitor (SSRI; OR = 2.30 [95% CI, 1.15 to 4.60]) were observed to improve the efficacy compared with placebo. For network meta-analysis, DOP was observed to improve the efficacy compared with placebo (OR = -0.84 [95% CI, -1.20 to -0.48]). Both direct and indirect evidence showed that several treatments, e.g., DOP, monoamine-oxidase inhibitor, serotonin-norepinephrine reuptake inhibitors, SSRI, and tricyclic antidepressants, significantly improved depressive symptoms. DOP and SSRI had good efficacy and improved symptoms considerably in dPD, but the adverse effect of these agents was needed to follow closely.