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Viruses May 2024Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response...
Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50-70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46-66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08-2.22]; = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3-37.8]; < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0-9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.
Topics: Humans; Male; Female; Reinfection; Adult; Substance Abuse, Intravenous; Sustained Virologic Response; Middle Aged; Antiviral Agents; Hepacivirus; Follow-Up Studies; Hepatitis C; Treatment Outcome; Hospitalization; RNA, Viral
PubMed: 38932151
DOI: 10.3390/v16060858 -
Pharmaceutics Jun 2024The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug...
The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug products. The aim was to optimize formulation compositions and process conditions to maintain nanoparticle size after tablet redispersion. The impact of drug load (22%, 33%, 44%) and type of drying protectant (mannitol, mannitol/trehalose mix (1:1), trehalose) on redispersibility and material powder properties were investigated. Moreover, compression analysis was performed assessing the influence of compaction pressure on primary nanocrystal redispersibility and tablet disintegration. Higher drug loads and lower drying protectant levels resulted in particle growth, confirming a drug load dependence on redispersibility behavior. Notably, all drying protectants showed similar protection properties at properly chosen drying process parameters (-dependent), except when VDD was used for mannitol formulations. Differences between the applied drying processes were observed in terms of downstream processing and tabletability: mannitol-containing formulations solidified via VDD showed an improved processability compared to formulations with trehalose. In conclusion, VDD is a promising drying technique that offers advantageous downstream processability compared to SD and represents an attractive novel processing technology for the pharmaceutical industry. As demonstrated in the present study, VDD combines higher yields with a leaner manufacturing process flow. The improved bulk properties provide enhanced tabletability and enable direct compression.
PubMed: 38931903
DOI: 10.3390/pharmaceutics16060782 -
Molecules (Basel, Switzerland) Jun 2024The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical...
The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of . In addition, the anti- activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS) and subjected to the microdilution method in 96-well plates against strains of , and . Myricitrin (93.89%; /; / 463.0876), gallic acid (99.9%; /; / 169.0142), and ellagic acid (94.2%; /; / 300.9988) were recovered. The polyphenolic fraction (62.67% (/) myricitrin) and the ellagic fraction (67.86% (/) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 μg/mL), suggesting an association between the majority constituents and the antifungal response of derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.
Topics: Polyphenols; Eugenia; Plant Leaves; Antifungal Agents; Plant Extracts; Microbial Sensitivity Tests; Candida; Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Chromatography, High Pressure Liquid; Gallic Acid
PubMed: 38930827
DOI: 10.3390/molecules29122761 -
Medicina (Kaunas, Lithuania) Jun 2024Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a...
Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose ( < 0.01)). However, there were no significant differences in outcomes between the two groups. Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.
Topics: Humans; Gabapentin; Male; Benzodiazepines; Female; Middle Aged; Substance Withdrawal Syndrome; Adult; Retrospective Studies; Treatment Outcome; Aged; Length of Stay
PubMed: 38929621
DOI: 10.3390/medicina60061004 -
International Journal of Environmental... Jun 2024Despite the lack of evidence, opioids are still routinely used as a solution to long-term management for chronic noncancer pain (CNCP). Given the significant risks... (Review)
Review
Despite the lack of evidence, opioids are still routinely used as a solution to long-term management for chronic noncancer pain (CNCP). Given the significant risks associated with long-term opioid use, including the increased number of unregulated opioid pills at large in the opioid ecosystem, opioid cessation or reduction may be the desired goal of the patient and clinician. Viable nonpharmacological interventions (NPIs) to complement and/or replace opioids for CNCP are needed. Comprehensive reviews that address the impact of NPIs to help adults with CNCP reduce opioid use safely are lacking. We conducted a literature search in PubMed, CINAHL, Embase, PsycINFO, and Scopus for studies published in English. The initial search was conducted in April 2021, and updated in January 2024. The literature search yielded 19,190 relevant articles. Thirty-nine studies met the eligibility criteria and underwent data extraction. Of these, nineteen (49%) were randomized controlled trials, eighteen (46%) were observational studies, and two (5%) were secondary analyses. Among adults with CNCP who use opioids for pain management, studies on mindfulness, yoga, educational programs, certain devices or digital technology, chiropractic, and combination NPIs suggest that they might be an effective approach for reducing both pain intensity and opioid use, but other NPIs did not show a significant effect (e.g., hypnosis, virtual reality). This review revealed there is a small to moderate body of literature demonstrating that some NPIs might be an effective and safe approach for reducing pain and opioid use, concurrently.
Topics: Humans; Chronic Pain; Analgesics, Opioid; Opioid-Related Disorders; Pain Management
PubMed: 38929040
DOI: 10.3390/ijerph21060794 -
International Journal of Environmental... Jun 2024We evaluated the impact of Medicaid policies in Virginia (VA), namely the Addiction and Recovery Treatment Services (ARTS) program and Medicaid expansion, on the number...
The Cumulative Effect of Expanding the Breadth and Scope of Coverage for Substance Use Disorder Treatment on Behavioral Health Acute Inpatient Admissions: Evidence from Virginia Medicaid.
We evaluated the impact of Medicaid policies in Virginia (VA), namely the Addiction and Recovery Treatment Services (ARTS) program and Medicaid expansion, on the number of behavioral health acute inpatient admissions from 2016 to 2019. We used Poisson fixed-effect event study regression and compared average proportional differences in admissions over three time periods: (1) prior to ARTS; (2) following ARTS but before Medicaid expansion; (3) post-Medicaid expansion. The number of behavioral health acute inpatient admissions decreased by 2.6% (95% CI [-5.1, -0.2]) in the first quarter of 2018 and this decrease gradually intensified by 4.9% (95% CI [-7.5, -2.4]) in the fourth quarter of 2018 compared to the second quarter of 2017 (beginning of ARTS) in VA relative to North Carolina (NC). Following the first quarter of 2019 (beginning of Medicaid expansion), decreases in VA admissions became larger relative to NC. The average proportional difference in admissions estimated a decrease of 2.7% (95% CI, [-4.1, -0.8]) after ARTS but before Medicaid expansion and a decrease of 2.9% (95% CI, [-6.1, 0.4]) post-Medicaid expansion compared to pre-ARTS in VA compared to NC. Behavioral health acute inpatient admissions in VA decreased following ARTS implementation, and the decrease became larger after Medicaid expansion.
Topics: Medicaid; Virginia; Humans; Substance-Related Disorders; United States; Hospitalization; Male; Adult; Female; Inpatients; Middle Aged
PubMed: 38929023
DOI: 10.3390/ijerph21060777 -
International Journal of Environmental... May 2024Drugged driving, the act of driving a vehicle under the influence of illicit drugs, by adolescents is a serious public health concern. Many factors contribute to this...
Drugged driving, the act of driving a vehicle under the influence of illicit drugs, by adolescents is a serious public health concern. Many factors contribute to this risk behavior, but much less is known regarding the role of parenting behaviors in this phenomenon. The purpose of this study was to examine specific parenting behaviors and their influence among a nationally representative sample of adolescents. Pooled data from the 2016-2019 National Survey on Drug Use and Health (NSDUH) among 17,520 adolescents ages 16-17 years old were analyzed. Differences were found in specific parenting behaviors and adolescent drugged/drunk driving, with parents not checking homework and not telling their children they are proud of them being the most influential. Findings from the present study may inform drugged driving prevention programs for parents and adolescents and enhance road safety interventions.
Topics: Humans; Adolescent; Parenting; United States; Female; Male; Driving Under the Influence; Adolescent Behavior; Automobile Driving; Risk-Taking; Substance-Related Disorders
PubMed: 38928941
DOI: 10.3390/ijerph21060695 -
Brain Sciences Jun 2024The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear...
BACKGROUND
The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear temporal sequence demonstrated previously.
METHODS
Data were derived from four waves (2011 baseline and 2013, 2015, and 2018 follow-ups) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants aged 45 years or older who had baseline data on both sarcopenia status and depressive symptoms in 2011 were included in the study. For the two cohort analyses, a total of 8092 adults without depressive symptoms and 11,292 participants without sarcopenia in 2011 were included. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Depressive symptoms were defined as a score of 20 or higher on the 10-item Center for Epidemiologic Studies Depressive Scale (CES-D-10). Cox proportional hazard regression models were conducted to examine the risk of depressive symptoms and sarcopenia risk, while cross-lagged panel models were used to examine the temporal sequence between depressive symptoms and sarcopenia over time.
RESULTS
During a total of 48,305.1 person-years follow-up, 1262 cases of incident depressive symptoms were identified. Sarcopenia exhibited a dose-response relationship with a higher risk of depressive symptoms (HR = 1.7, 95%CI: 1.2-2.3 for sarcopenia, and HR = 1.5, 95%CI: 1.2-1.8 for possible sarcopenia, trend < 0.001). In the second cohort analysis, 240 incident sarcopenia cases were identified over 39,621.1 person-years. Depressive symptoms (HR = 1.5, 95%CI: 1.2-2.0) are significantly associated with a higher risk of developing sarcopenia after multivariable adjustment ( < 0.001, Cross-lagged panel analyses demonstrated that depressive symptoms were associated with subsequent sarcopenia (β = 0.003, < 0.001). Simultaneously, baseline sarcopenia was also associated with subsequent depressive symptoms (β = 0.428, < 0.001).
CONCLUSION
This study identified a bidirectional relationship between depressive symptoms and sarcopenia. It seems more probable that baseline sarcopenia is associated with subsequent depressive symptoms in a stronger pattern than the reverse pathway. The interlinkage indicated that maintaining normal muscle mass and strength may serve as a crucial intervention strategy for alleviating mood disorders.
PubMed: 38928593
DOI: 10.3390/brainsci14060593 -
International Journal of Molecular... Jun 2024Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the...
Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the mesolimbic dopaminergic reward system, has been postulated to play a pivotal role in the underlying mechanism of alcohol dependence. The study aims to analyse the association of the rs6295 polymorphism of the gene in women with alcohol use disorder and the association of personality traits with the development of alcohol dependence, as well as the interaction of the rs6295, personality traits, and anxiety with alcohol dependence in women. The study group consisted of 213 female volunteers: 101 with alcohol use disorder and 112 controls. NEO Five-Factor and State-Trait Anxiety Inventories were applied for psychometric testing. Genotyping of rs6295 was performed by real-time PCR. We did not observe significant differences in rs6295 genotypes ( = 0.2709) or allele distribution ( = 0.4513). The AUD subjects scored higher on the anxiety trait ( < 0.0001) and anxiety state ( < 0.0001) scales, as well as on the neuroticism ( < 0.0001) and openness ( = 0134) scales. Significantly lower scores were obtained by the AUD subjects on the extraversion ( < 0.0001), agreeability ( < 0.0001), and conscientiousness ( < 0.0001) scales. Additionally, we observed a significant effect of rs6295 genotype interaction and alcohol dependency, or lack thereof, on the openness scale ( = 0.0016). In summary, this study offers a comprehensive overview of alcohol dependence among women. It offers valuable insights into this complex topic, contributing to a more nuanced understanding of substance use among this specific demographic. Additionally, these findings may have implications for developing prevention and intervention strategies tailored to individual genetic and, most importantly, personality and anxiety differences.
Topics: Humans; Female; Receptor, Serotonin, 5-HT1A; Alcoholism; Personality; Adult; Anxiety; Middle Aged; Polymorphism, Single Nucleotide; Genotype; Genetic Predisposition to Disease; Alleles; Genetic Association Studies; Case-Control Studies
PubMed: 38928270
DOI: 10.3390/ijms25126563 -
International Journal of Molecular... Jun 2024Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory... (Review)
Review
Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.
Topics: Humans; Glutamic Acid; Mental Disorders; Animals; Neurodevelopmental Disorders; Neuronal Plasticity; Brain; Adult; Substance-Related Disorders; Autism Spectrum Disorder
PubMed: 38928227
DOI: 10.3390/ijms25126521