BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*

BACKGROUND: Epidural steroid injections (ESIs) have been widely used in managing spinal pain. Dexamethasone has recently emerged as a useful drug in this setting, relative to particulate steroids, although the associated systemic effects have not been fully elucidated. This study aimed to investigate the incidences and types of systemic effects after fluoroscopically guided ESI with dexamethasone. METHODS: This retrospective study included 888 ESIs with dexamethasone (fluoroscopically guided at the cervical and lumbosacral levels) performed on 825 patients during January to June 2017. Data regarding systemic effects were collected via telephone interviews using a standardized questionnaire at 2 weeks after the procedure. Data on patient demographic, clinical, and procedural characteristics were collected and analyzed to identify factors that were associated with systemic effects. All statistical analyses were performed using the chi-squared test. RESULTS: Among the 825 patients, 40 patients (4.8%) experienced systemic effects during the 2-week follow-up period. The most common systemic effect was facial flushing (12 patients, 1.5%), which was followed by urticaria (7 patients, 0.8%) and insomnia (7 patients, 0.8%). A history of spine surgery was significantly associated with the occurrence of systemic effects (P = 0.036). Systemic effects were significantly more common for injections at the cervical level than at the lumbar level (P = 0.019). CONCLUSIONS: Approximately 4.8% of the patients who underwent ESI with dexamethasone experienced minor and transient systemic effects. These effects were more common in patients who had undergone a previous spine surgery or received a cervical ESI.
Dexamethasone ; Drug-Related Side Effects and Adverse Reactions ; Epidural Space ; Fluoroscopy ; Flushing ; Follow-Up Studies ; Humans ; Incidence ; Interviews as Topic ; Low Back Pain ; Retrospective Studies ; Sleep Initiation and Maintenance Disorders ; Spine ; Steroids ; Urticaria

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.
Acoustic Stimulation ; Analysis of Variance ; Animals ; Dose-Response Relationship, Drug ; Electroencephalography ; Excitatory Amino Acid Antagonists ; pharmacology ; Gamma Rhythm ; drug effects ; Ketamine ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sensory Gating ; drug effects ; Sleep Stages ; drug effects ; Statistics as Topic ; Time Factors ; Wakefulness ; drug effects

OBJECTIVETo assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.

METHODSCaffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.

RESULTSAIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.

CONCLUSIONAIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

Animals ; Caffeine ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drosophila melanogaster ; drug effects ; physiology ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Mutation ; genetics ; Potassium Channels ; genetics ; Sleep ; drug effects ; Sleep Initiation and Maintenance Disorders ; drug therapy ; Wakefulness ; drug effects

Functional dyspepsia is one of the most common bowel disorders as prevalent of 7.7% Korean population. The cardinal manifestations include bothersome postprandial fullness, early satiation, epigastric burning or pain. These features are chronic and should be presented recurrently with no other compatible organic disease to explain the symptoms. Even though it is not life-shortening, functional dyspepsia usually make the health-related quality of life worse especially if other functional bowel disorder coexist. The coexistence of functional bowel disorders is called as 'overlap syndrome'. Anxiety, somatization and insomnia is more prevalent in overlap syndrome compared with sole functional bowel disorder. Therefore, it is worthwhile that physician interviews and elucidates whether the dyspeptic patient had other kinds of functional bowel disorders, and manages the underlying psychotic pathology. Placebo effect is large in functional dyspepsia, and there is only four kinds of prokinetics that is proven to be superior to placebo. Adverse events relating prolonged administration of prokinetics sometimes fatal or irreversible, physician willing to describe prokinetics should be familiar to the possible adverse effects and the relating risk factors. Pathologic acid reflux is not uncommon in functional dyspepsia, and acid-suppressant is equivalent to the prokientics in most of dyspeptic patients.
Anxiety ; Burns ; Drug-Related Side Effects and Adverse Reactions ; Dyspepsia* ; Humans ; Pathology ; Placebo Effect ; Quality of Life ; Risk Factors ; Satiation ; Sleep Initiation and Maintenance Disorders

PURPOSE: The aim of this study was to evaluate the effects and safety of a sleep aid for postoperative analgesia in patients undergoing arthroscopic rotator cuff repair. MATERIALS AND METHODS: Seventy-eight patients were prospectively assigned to either the zolpidem group (multimodal analgesia+zolpidem; 39 patients) or the control group (multimodal analgesia; 39 patients). Self-rated pain levels were assessed twice a day using a visual analog scale (VAS). The need for additional rescue analgesic, duration of functional recovery, and adverse effects were assessed for the first 5 days after surgery. RESULTS: The mean number of times that additional rescue analgesic was required during 5 days after surgery was 2.1+/-2.0 in the zolpidem group and 3.3+/-2.8 in the control group, a significant difference. There were no significant differences between the two groups in mean VAS pain scores during the first 5 days after surgery, although the zolpidem group had lower VAS pain scores than the control group. Additionally, there were no significant differences in duration of functional recovery and adverse effects between the two groups. CONCLUSION: The use of zolpidem for analgesia after arthroscopic rotator cuff repair provided a significant reduction in the need for rescue analgesic without increasing adverse effects. Nevertheless, mean VAS pain scores during the first 5 days after surgery did not differ between the zolpidem group and the control group.
Adult ; Analgesia/*methods ; Analgesics/*therapeutic use ; Arthroscopy/*adverse effects ; Female ; Humans ; Hypnotics and Sedatives/*therapeutic use ; Male ; Middle Aged ; Pain Management ; Pain Measurement ; Pain, Postoperative/drug therapy/etiology/*prevention & control ; Postoperative Period ; Prospective Studies ; Pyridines/*therapeutic use ; Rotator Cuff/injuries/*surgery ; Sleep/drug effects ; Treatment Outcome ; Visual Analog Scale

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.
Adult ; Alleles ; Anaphylaxis* ; Asthma ; Basophil Degranulation Test ; Basophils ; Codeine* ; Constipation ; Cough ; Cytochrome P-450 CYP2D6 ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Eating ; Euphoria ; Female ; Food Hypersensitivity ; Genotype ; Histamine ; Histamine Release ; Humans ; Nausea ; Respiratory Tract Infections ; Rhinitis ; Seafood ; Skin ; Sleep Stages ; Thorax ; Urticaria

Brain ; physiology ; Child ; Dyssomnias ; drug therapy ; epidemiology ; etiology ; Humans ; Infant ; Sleep ; drug effects ; Vitamin D ; administration & dosage ; analogs & derivatives ; blood ; Vitamin D Deficiency ; complications ; drug therapy ; epidemiology

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.
Animals ; Brain ; drug effects ; physiology ; Dopamine ; metabolism ; Electroencephalography ; Hypnotics and Sedatives ; pharmacology ; Mice ; Motor Activity ; drug effects ; Serotonin ; metabolism ; Sleep ; drug effects

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
Administration, Intravenous ; Administration, Oral ; Analgesia ; Analgesics, Non-Narcotic ; Anticonvulsants ; Antidepressive Agents ; Calcium ; Carbamazepine ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Hiccup ; Long-Term Potentiation ; Molecular Mechanisms of Pharmacological Action ; N-Methylaspartate ; Nausea ; Nefopam* ; Neuralgia* ; Neurotransmitter Agents ; Nociceptive Pain ; Norepinephrine ; Shivering ; Sleep Stages ; Sodium Channels ; Sweat ; Sweating ; Tachycardia