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The International Journal of... Jun 2023Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association...
Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy. Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation. People who smoked drugs (PWSD) comprised 54.8% ( = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10-1.97; 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22-4.34; = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62-1.87; = 0.799) was not associated with increased cavitation. PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.
Topics: Humans; Tuberculosis, Pulmonary; Smoke; Mycobacterium; Smoking; Tobacco Use; Sputum; HIV Infections
PubMed: 37231597
DOI: 10.5588/ijtld.22.0650 -
The South African Journal of Psychiatry... 2016Substance use and psychiatric disorders cause significant burden of disease in low- and middle-income countries. Co-morbid psychopathology and longer duration of...
BACKGROUND
Substance use and psychiatric disorders cause significant burden of disease in low- and middle-income countries. Co-morbid psychopathology and longer duration of untreated psychosis (DUP) can negatively affect treatment outcomes.
OBJECTIVES
The study assessed substance use amongst adults with severe mental illness receiving services at a regional psychiatric hospital in KwaZulu-Natal (South Africa). We describe the prevalence and correlates of lifetime substance use and examine the association between substance use and DUP.
METHODS
A cross-sectional survey recruited adults diagnosed with severe mental illness and assessed lifetime and past 3-month substance use using the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test. Regression analyses were conducted to determine associations between lifetime substance use (other than alcohol and tobacco) and DUP as measured by the World Health Organization Encounter Form.
RESULTS
Amongst 87 participants, alcohol (81.6%), tobacco (75.6%) and cannabis (49.4%) were the most common substances reported for lifetime use. Risk of health-related problems (health, social, financial, legal and relationship) of cannabis use was associated with younger age, single marital status and lower education. Adjusted regression analyses indicated that use of amphetamines and methaqualone is associated with longer DUP.
CONCLUSIONS
Substance use is prevalent amongst psychiatric patients in KwaZulu-Natal and may contribute to longer DUP. Mental health services in this region should address co-morbid substance use and psychiatric disorders.
PubMed: 27307782
DOI: 10.4102/sajpsychiatry.v22i1.852 -
PloS One 2022People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess...
People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.
Topics: Adolescent; Adult; Contact Tracing; Cross-Sectional Studies; DNA, Bacterial; Diphenhydramine; Drug Combinations; Drug Users; Female; Humans; Male; Methamphetamine; Methaqualone; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Registries; South Africa; Sputum; Surveys and Questionnaires; Tuberculosis; Young Adult
PubMed: 35167586
DOI: 10.1371/journal.pone.0262440 -
Acta Crystallographica. Section E,... Mar 2012In the title methaqua-lone analogue, C(16)H(13)N(3)O(3), the 2-tolyl group is almost orthogonal [dihedral angle = 85.20 (5)°] to the fused ring system (r.m.s....
In the title methaqua-lone analogue, C(16)H(13)N(3)O(3), the 2-tolyl group is almost orthogonal [dihedral angle = 85.20 (5)°] to the fused ring system (r.m.s. deviation of fitted non-H atoms = 0.029 Å). In the crystal, twofold symmetry generates two-mol-ecule aggregates linked by C-H⋯O and π-π inter-actions [ring centroid-centroid distance = 3.4967 (6) Å].
PubMed: 22412718
DOI: 10.1107/S1600536812007350 -
Molecular Pharmacology Aug 2015In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an...
In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2,3,5β2,3γ2S GABAA receptors (GABAARs) expressed in Xenopus oocytes, whereas it displayed highly diverse functionalities at the α4,6β1,2,3δ GABAAR subtypes, ranging from inactivity (α4β1δ), through negative (α6β1δ) or positive allosteric modulation (α4β2δ, α6β2,3δ), to superagonism (α4β3δ). Methaqualone did not interact with the benzodiazepine, barbiturate, or neurosteroid binding sites in the GABAAR. Instead, the compound is proposed to act through the transmembrane β((+))/α((-)) subunit interface of the receptor, possibly targeting a site overlapping with that of the general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of methaqualone was further investigated in multichannel recordings from primary frontal cortex networks, where the overall activity changes induced by the compound at 1-100 μM concentrations were quite similar to those mediated by other CNS depressants. Finally, the free methaqualone concentrations in the mouse brain arising from doses producing significant in vivo effects in assays for locomotion and anticonvulsant activity correlated fairly well with its potencies as a modulator at the recombinant GABAARs. Hence, we propose that the multifaceted functional properties exhibited by methaqualone at GABAARs give rise to its effects as a therapeutic and recreational drug.
Topics: Animals; Binding Sites; Brain; Humans; Hypnotics and Sedatives; Illicit Drugs; Locomotion; Male; Methaqualone; Mice; Mutation; Receptors, GABA-A; Xenopus
PubMed: 26056160
DOI: 10.1124/mol.115.099291 -
British Medical Journal Aug 1970Two experiments compatible with that used to investigate the effect of clinical doses (200 mg.) of amylobarbitone were set up to investigate the effects of clinical... (Clinical Trial)
Clinical Trial
Two experiments compatible with that used to investigate the effect of clinical doses (200 mg.) of amylobarbitone were set up to investigate the effects of clinical doses of chloral hydrate (800 mg.), dichloral phenazone (1,300 mg.), and Mandrax (methaqualone 250 mg. and diphenhydramine 25 mg.) over a period of one to two weeks.Four healthy male subjects were used in each experiment and received placebo or drug throughout a period of six to eight weeks when control records, drug records, and drug withdrawal records were obtained.Chloral hydrate was found to depress rapid eye movement (R.E.M.) sleep appreciably though less consistently than amylobarbitone. No withdrawal R.E.M. sleep rebound was found.Neither dichloralphenazone nor Mandrax was found consistently to depress R.E.M. sleep, though occasional nights when R.E.M. sleep was low occurred more often with Mandrax.In the light of other experiments it is postulated that there exists a "threshold" in the dose of a hypnotic, and that when this is exceeded the drug will produce R.E.M. reduction. Thus it may be possible to prescribe a drug which is clinically useful while avoiding withdrawal effects.
Topics: Adult; Amobarbital; Antipyrine; Chloral Hydrate; Diphenhydramine; Drug Tolerance; Humans; Male; Methaqualone; Placebos; Sleep; Sleep, REM; Substance Withdrawal Syndrome
PubMed: 4318020
DOI: 10.1136/bmj.3.5718.310 -
The South African Journal of Psychiatry... 2020Substance use disorders (SUDs) occur frequently in patients with psychotic disorders and have been associated with various demographic and clinical correlates. There is...
BACKGROUND
Substance use disorders (SUDs) occur frequently in patients with psychotic disorders and have been associated with various demographic and clinical correlates. There is an absence of research on the prevalence and clinical correlates of SUDs in psychotic disorders in low-and-middle-income countries (LMICs).
AIM
We aimed to determine the prevalence and correlates of SUDs in psychotic disorders.
SETTING
Patients attending a large secondary-level psychiatric hospital in Cape Town South Africa.
METHODS
We used the Structured Clinical Interview for DSM-IV (SCID-I) to determine psychiatric and substance use diagnoses, depressive, anxiety, obsessive-compulsive and post-traumatic symptoms. We used logistic regression models to determine significant predictors of SUDs.
RESULTS
In total sample ( = 248), 55.6% of participants had any SUD, 34.3% had cannabis use disorders, 30.6% alcohol use disorders, 27.4% methamphetamine use disorders, 10.4% methaqualone use disorders and 4.8% had other SUDs. There were significant associations with male sex for most SUDs, with younger age and Coloured ethnicity for methamphetamine use disorders, and with lower educational attainment for cannabis use disorders. Anxiety symptoms and suicide attempts were significantly associated with alcohol use disorders; a diagnosis of a substance induced psychosis with cannabis and methamphetamine use disorders. Across most SUDs legal problems and criminal involvement were significantly increased.
CONCLUSION
This study found a high prevalence and wide distribution of SUDs in patients with psychotic disorders, consistent with previous work from high income countries. Given clinical correlates, in individuals with psychotic disorders and SUDs it is important to assess anxiety symptoms, suicidality and criminal involvement.
PubMed: 32832129
DOI: 10.4102/sajpsychiatry.v26i0.1473 -
BMJ Open Feb 2019Sexual and physical trauma and substance use are intersecting risks for HIV among young women. This study assesses the feasibility, acceptability and preliminary effects...
OBJECTIVES
Sexual and physical trauma and substance use are intersecting risks for HIV among young women. This study assesses the feasibility, acceptability and preliminary effects of a novel trauma-informed substance use and sexual risk reduction intervention for young South African women.
DESIGN
A single arm feasibility test and qualitative interviews of participants.
PARTICIPANTS
Sixty women, between 18 and 25 years of age, who reported trauma exposure, substance use and recent condom-less sex were recruited. Twenty participants were randomly selected for qualitative interviews.
INTERVENTION
A six-session group-based intervention.
MAIN OUTCOME MEASURES
We examined the proportion of women who provided consent, completed counselling and were retained in the study. Qualitative interviews explored intervention acceptability. Preliminary effects of the intervention on substance use, mental health (depression, psychological distress and trauma symptoms) and sexual risk outcomes (STI symptoms, number of partners and condomless sex) were explored.
RESULTS
Of the 66 eligible women, 91% were enrolled. Intervention completion rates were low; 35% attended all sessions. On average, participants attended four sessions (M=3.8, SD=1.3). A 93% follow-up rate was achieved at the 3-month endpoint. In this single group design, reductions in the proportion of participants who tested positive for methamphetamine, cannabis and methaqualone were observed at the 3-month endpoint. Symptoms of depression, psychological distress and trauma; number of STI symptoms; and number of sexual partners also decreased. Outcomes were similar for participants who completed up to four and those who completed five or more sessions. Participants thought the intervention was highly beneficial and proposed modifications to enhance acceptability.
CONCLUSIONS
This novel intervention seems acceptable and holds potential benefits for trauma-exposed women who use substances. Truncating the intervention may enhance the likelihood of its implementation. The efficacy of the intervention for improving substance use, sexual risk and mental health outcomes requires testing in a controlled design.
Topics: Adolescent; Adult; Counseling; Feasibility Studies; Female; Health Knowledge, Attitudes, Practice; Humans; Mental Health; Patient Education as Topic; Psychological Trauma; Qualitative Research; Risk Reduction Behavior; South Africa; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Unsafe Sex; Young Adult
PubMed: 30782918
DOI: 10.1136/bmjopen-2018-024776 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2013Methylmethaqualone is a sedative designer drug created by adding a methyl group to the 3-phenyl ring of methaqualone, and is at present not subject to restrictive...
Methylmethaqualone is a sedative designer drug created by adding a methyl group to the 3-phenyl ring of methaqualone, and is at present not subject to restrictive regulation in many countries. To our knowledge, no case of methylmethaqualone abuse has been published to date in the scientific literature, and the only sources of information are users' reports on Web discussion forums and data from preclinical animal studies. We report a case of oral methylmethaqualone abuse confirmed by liquid chromatography tandem mass spectrometry in a 24-year-old previously healthy Caucasian male. Observed symptoms and signs such as central nervous system depression alternating with excitation, psychomotor agitation, muscle hyperactivity, and tachycardia were compatible with methaqualone-induced adverse effects. Except for the mild tachycardia (115 beats/min), other vital signs were normal: blood pressure 134/89 mmHg, body temperature 36.2°C (97.16°F), and peripheral oxygen saturation 99% while breathing room air. The ECG showed no prolongation of the QT interval and the QRS duration was normal. Laboratory analysis revealed a slight increase in creatine kinase (368 U/L) and alanine aminotransferase (90 U/L) serum concentrations. Blood alcohol concentration was 0.32 g/L. Methylmethaqualone was identified in a serum sample collected on admission which was analyzed by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction. After a few days the patient ingested the same amount of substance with identical symptoms. Based on the chemical structure and animal data, and according to this case report and users' Web reports, methylmethaqualone appears to have a similar acute toxicity profile to methaqualone, with marked psychomotor stimulation. Symptoms of acute toxicity can be expected to resolve with supportive care.
Topics: Adult; Chromatography, High Pressure Liquid; Designer Drugs; Humans; Hypnotics and Sedatives; Male; Methaqualone; Methylation; Neurotoxicity Syndromes; Severity of Illness Index; Tandem Mass Spectrometry; Treatment Outcome; Young Adult
PubMed: 23298217
DOI: 10.3109/15563650.2012.758855 -
British Medical Journal Apr 1963
Topics: Humans; Hypnotics and Sedatives; Methaqualone
PubMed: 14016566
DOI: 10.1136/bmj.1.5335.949-b