Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case’s characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.
Lung Neoplasms ; Conscious Sedation ; Dexmedetomidine ; Midazolam ; Fentanyl ; Lidocaine ; Dextromethorphan

INTRODUCTION: Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression. METHODS: A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted. RESULTS: The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug. CONCLUSION In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.
Adolescent ; Humans ; Male ; Adult ; Middle Aged ; Child ; Young Adult ; Female ; Cannabis ; Singapore/epidemiology* ; Heroin ; Substance-Related Disorders/epidemiology* ; Illicit Drugs

Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q₁, Q₃)] of 0.40 (0.22-0.8) ng·g^-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q₁, Q₃)] of 0.13 (0.09, 0.17) ng·g^-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant^-1·day^-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q₁, Q₃)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
Humans ; Beijing ; Wastewater-Based Epidemiological Monitoring ; Sewage/analysis* ; Wastewater ; Ketamine/analysis* ; Codeine/analysis* ; Methadone/analysis* ; Water Pollutants, Chemical/analysis*

OBJECTIVE: To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet. METHODS: A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups. RESULTS: Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05). CONCLUSION On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.
Humans ; Cancer Pain ; Oxycodone ; Quality of Life ; Lung Neoplasms ; Pain ; Acupuncture Therapy ; Adjuvants, Immunologic ; Lung ; Analgesics

BACKGROUND: Managing acute postoperative pain is challenging for anesthesiologists, surgeons, and patients, leading to adverse events despite making significant progress. Patient-controlled intravenous analgesia (PCIA) is a recommended solution, where oxycodone has depicted unique advantages in recent years. However, controversy still exists in clinical practice and this study aimed to compare two drugs in PCIA. METHODS: We performed a literature search in PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases up to December 2020 to select specific randomized controlled trials (RCTs) comparing the efficacy of oxycodone with sufentanil in PCIA. The analgesic effect was the primary outcome and the secondary outcome included PCIA consumption, the Ramsay sedation scale, patients' satisfaction and side effects. RESULTS: Fifteen RCTs were included in the meta-analysis. Compared with sufentanil, oxycodone showed lower Numerical Rating Scale scores (mean difference [MD] = -0.71, 95% confidence interval [CI]: -1.01 to -0.41; P < 0.001; I2 = 93%), demonstrated better relief from visceral pain (MD = -1.22, 95% CI: -1.58 to -0.85; P < 0.001; I2 = 90%), promoted a deeper sedative level as confirmed by the Ramsay Score (MD = 0.77, 95% CI: 0.35-1.19; P < 0.001; I2 = 97%), and resulted in fewer side effects (odds ratio [OR] = 0.46, 95% CI: 0.35-0.60; P < 0.001; I2 = 11%). There was no statistical difference in the degree of patients' satisfaction (OR = 1.13, 95% CI: 0.88-1.44; P = 0.33; I2 = 72%) and drug consumption (MD = -5.55, 95% CI: -14.18 to 3.08; P = 0.21; I2 = 93%). CONCLUSION: Oxycodone improves postoperative analgesia and causes fewer adverse effects, and could be recommended for PCIA, especially after abdominal surgeries. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; CRD42021229973.
Humans ; Oxycodone/therapeutic use* ; Sufentanil/therapeutic use* ; Randomized Controlled Trials as Topic ; Pain, Postoperative/drug therapy* ; Drug-Related Side Effects and Adverse Reactions ; Analgesia, Patient-Controlled

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

INTRODUCTION: Misuse of prescription medicines and the harms associated with such use are growing threats across the world. There is currently, however, limited data on the extent of prescription medicine misuse in Singapore and whether this is a current threat in the country. METHODS: An online survey, limited to 1,000 individuals (aged 21 years and over) who were residents in Singapore, was administered through a survey panel company in September 2015. The survey collected information on participant demographics, and their awareness, self-reported lifetime and past-year misuse of commonly available prescription medicines in Singapore as well as the use of a range of recreational drugs and novel psychoactive substances (NPS). RESULTS: Lifetime (6.7%) and past-year (4.8%) misuse of any prescription medicine was comparable to lifetime (6.0%) and past-year (3.0%) use of any recreational drugs/NPS. The top five prescription medicines for lifetime misuse were: diazepam (2.7%); codeine (2.3%); dhasedyl (promethazine, codeine and ephedrine; 1.6%); panadeine (paracetamol and codeine; 1.5%); and methylphenidate (1.2%). The top five drugs for past-year misuse were: diazepam (1.6%); codeine (0.9%); panadeine (0.7%); alprazolam (0.6%); baclofen (0.6%); and gabapentin (0.6%). CONCLUSION Misuse of prescription medicine in Singapore was common, with prevalence comparable to the use of recreational drugs/NPS. A common source for misused drugs was physicians. Further studies are required to determine whether this is more widespread in Singapore and establish the different forms of drug diversion, so that appropriate prevention strategies can be implemented.
Humans ; Illicit Drugs/adverse effects* ; Public Health ; Singapore/epidemiology* ; Substance-Related Disorders/drug therapy* ; Prescription Drugs/adverse effects* ; Codeine ; Diazepam ; Prescriptions

OBJECTIVE: This study aimed to investigate the effects of Montanide ISA-720 and Naloxone (NLX) in Hepatitis B surface antigen (HBsAg) vaccine formulation on cytokine and long-lasting antibody responses. METHODS: First, the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10 mg/kg. The experimental mice were immunized three times at a 2-week interval, and then IL-4, IL-2, TNF-α, and IFN-γ cytokines; long-lasting IgG antibody responses 220 days after the last shot; and IgG1/IgG2a isotypes were assessed by ELISA. RESULTS: The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups, whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses. In addition, NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio. Moreover, HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses, and NLX in Alum- and MON720-based vaccines induced long-lasting antibody responses. CONCLUSION NLX in Alum-based vaccine decreased IL-4 cytokine response, increased IL-2/IL-4 cytokine ratio, and improved long-lasting humoral immune responses in both vaccine formulations. Therefore, the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.
Adjuvants, Immunologic/pharmacology* ; Alum Compounds ; Animals ; Cytokines ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Immunity, Humoral ; Immunoglobulin G ; Interleukin-2 ; Interleukin-4 ; Mice ; Mice, Inbred BALB C ; Mineral Oil ; Naloxone/pharmacology* ; Tumor Necrosis Factor-alpha

This study aims to explore the effect of Jinzhen Oral Liquid(JOL) on cough after infection in rats and the mechanism. To be specific, a total of 60 male SD rats were classified into 6 groups: normal group(equivalent volume of distilled water, ig), model group(equivalent volume of distilled water, ig), Dextromethorphan Hydrobromide Oral Solution group(3.67 mL·kg~(-1), ig), high-, medium-, and low-dose JOL groups(11.34, 5.67, and 2.84 mL·kg~(-1), respectively, ig). Lipopolysaccharide(LPS, nasal drip), smoking, and capsaicin(nebulization) were employed to induce cough after infection in rats except the normal group. Administration began on the 19 th day and lasted 7 days. Capsaicin(nebulization) was used to stimulate cough 1 h after the last administration and the cough frequency and cough incubation period in rats were recorded. The pathological morphology of lung tissue was observed based on hematoxylin-eosin(HE) staining. Immunohistochemistry(IHC) was used to detect the specific expression of transient receptor potential vanilloid 1(Trpv1), nerve growth factor(NGF), tropomyosin receptor kinase A(TrkA), and phosphorylated-p38 mitogen-activated protein kinase(p-p38 MAPK) in lung tissue, Western blot the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and real-time fluorescent quantitative polymerase chain reaction(real-time PCR) the mRNA expression of Trpv1, NGF, and TrkA. The results showed that model group demonstrated significantly high cough frequency, obvious proliferation and inflammatory cell infiltration in lung tissue, significantly enhanced positive protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue and significant increase in the mRNA expression of Trpv1, NGF, and TrkA compared with the normal group. Compared with the model group, JOL can significantly reduce the cough frequency, alleviate the pathological changes of lung tissue, and decrease the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and high-dose and medium-dose JOL can significantly lower the mRNA expression of Trpv1, NGF, and TrkA. This study revealed that JOL can effectively inhibit Trpv1 pathway-related proteins and improve cough after infection. The mechanism is that it reduces the expression of NGF, TrkA, and p-p38 MAPK in lung tissue, thereby decreasing the expression of Trpv1 and cough sensitivity.
Animals ; Capsaicin/adverse effects* ; Cough/drug therapy* ; Dextromethorphan/adverse effects* ; Eosine Yellowish-(YS)/adverse effects* ; Hematoxylin ; Lipopolysaccharides/adverse effects* ; Male ; Medicine, Chinese Traditional ; Nerve Growth Factor/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA/metabolism* ; TRPV Cation Channels/metabolism* ; Tropomyosin/metabolism* ; Water/metabolism* ; p38 Mitogen-Activated Protein Kinases/metabolism*

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
Drug Delivery Systems/methods* ; Drug Liberation ; Indocyanine Green ; Morphinans ; Needles ; Polyethylene Glycols