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  • BMJ  (6)
  • 2020-2024  (6)
  • 1
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    Online Resource
    Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy
    BMJ ; 2020
    In:  Journal of Medical Genetics Vol. 57, No. 2 ( 2020-02), p. 124-131
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 57, No. 2 ( 2020-02), p. 124-131
    Abstract: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD. Methods ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed. Results Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2–8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events. Conclusions Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2019-106132
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 220881-7
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 2
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    Executive dysfunction and risk of suicide in older adults: a population-based prospective cohort study
    BMJ ; 2021
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 92, No. 5 ( 2021-05), p. 528-533
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 92, No. 5 ( 2021-05), p. 528-533
    Abstract: It is uncertain what factors increases the risk of suicide in older adults without depression, and it is unknown whether executive dysfunction (ED) is one of those factors. We aimed to examine the effect of ED on the risk of suicide in non-demented older adults without depression. Methods In an ongoing population-based prospective cohort of Korean older adults, we identified suicide using the National Mortality Database and suicidal ideation or attempt (SIA) based on the Korean version of the Mini International Neuropsychiatric Interview. We defined ED as performing below −1.5 SD of age-adjusted, gender-adjusted and education-adjusted norms in any of following tests: Frontal Assessment Battery, Trail Making Test A, Digit Span Test or Verbal Fluency Test. Results The mean age of the 4791 participants at baseline was 69.7 (SD 6.4) years, and 57.1% of them were women (mean follow-up duration=4.9 years). ED at baseline increased the risk of suicide by about seven times (HR 7.20, 95% CI 1.84 to 28.12, p=0.005) but did not change the risk of SIA. However, cognitive impairment without ED did not change the risks of suicide and SIA. In participants with ED, being aged 75 years or above, living alone, and having a low socioeconomic status were associated with the risk of suicide. Conclusion ED is a strong risk factor of late life suicide independent from depression, particularly in very old adults living in disadvantaged environments.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2020-324390
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1480429-3
    detail.hit.zdb_id: 3087-9
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  • 3
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    Comparison of the incidence of intravascular injection using the Tuohy and Quincke needles during ultrasound-guided caudal epidural block: a prospective randomized controlled study
    BMJ ; 2024
    In:  Regional Anesthesia & Pain Medicine Vol. 49, No. 1 ( 2024-01), p. 17-22
    Details
    In: Regional Anesthesia & Pain Medicine, BMJ, Vol. 49, No. 1 ( 2024-01), p. 17-22
    Abstract: Intravascular injection of a local anesthetic can lead to life-threatening complications, such as deficits in neurological function after caudal epidural block. This study aimed to determine whether the intravascular injection rate of the Tuohy needle is lower than that of the Quincke needle during an ultrasound-guided caudal block. Methods Two-hundred and thirty patients were randomized into the Quincke (n=115) and the Tuohy (n=115) needle groups. The randomly selected needle was introduced at a 45° angle until it penetrated the sacrococcygeal ligament under ultrasound guidance, and intravenous injections were analyzed using contrast-dyed digital subtraction angiography. The relationship between the incidence of intravascular injection and independent variables, including needle type, patient demographics, history of lumbosacral surgery, use of anticoagulants, anatomic variables of the sacrum, presence of bony contact during the procedure, and the number of needle repositioning under ultrasound guidance, were examined. Results Intravascular uptake of contrast medium was surveyed in 25/230 (10.9%) caudal blocks using digital subtraction angiography (DSA). The incidence of intravascular uptake was 13.9% (16/115) using the Quincke needle and 7.8% (9/115) using the Tuohy needle (p=0.14). Although the needle tip type was not associated with the rate of intravascular injection, the occurrence of bony contact during the procedure demonstrated a relationship with the intravenous injection (p 〈 0.01). Conclusions The overall incidence of inadvertent intravascular injections during ultrasound-guided caudal block confirmed using DSA was 10.9%. Tuohy needles did not reduce intravascular injection rates during the ultrasound-guided caudal block. Trial registration number NCT05504590 .
    Type of Medium: Online Resource
    ISSN: 1098-7339 , 1532-8651
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/rapm-2023-104504
    DOI: 10.1136/rapm-2023-104504.supp1
    DOI: 10.1136/rapm-2023-104504.supp2
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2028901-7
    detail.hit.zdb_id: 1425299-5
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  • 4
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    Online Resource
    Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes
    BMJ ; 2020
    In:  BMJ Open Diabetes Research & Care Vol. 8, No. 1 ( 2020-10), p. e001372-
    Details
    In: BMJ Open Diabetes Research & Care, BMJ, Vol. 8, No. 1 ( 2020-10), p. e001372-
    Abstract: Recent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date. Research design and methods We prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery. Results The copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM. Conclusion These results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.
    Type of Medium: Online Resource
    ISSN: 2052-4897
    URL: Article
    DOI: 10.1136/bmjdrc-2020-001372
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2732918-5
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  • 5
    Online Resource
    Online Resource
    Effect of diabetes on exosomal miRNA profile in patients with obesity
    BMJ ; 2020
    In:  BMJ Open Diabetes Research & Care Vol. 8, No. 1 ( 2020-09), p. e001403-
    Details
    In: BMJ Open Diabetes Research & Care, BMJ, Vol. 8, No. 1 ( 2020-09), p. e001403-
    Abstract: Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. T2DM increases the risk of cardiovascular-related death. We investigated changes in circulating exosomal microRNA (miRNA) profiles in patients with DM with obesity compared with patients without DM with obesity. Research design and methods This prospective study involved 29 patients with obesity (patients without DM=16, patients with DM=13) and healthy volunteers (HVs) (n=18). We measured circulating levels of exosomal miRNAs by next-generation sequencing and compared miRNA levels across the three groups. Results The expression levels of 25 miRNAs (upregulated=14, downregulated=11) differed between patients with obesity with DM and patients with obesity without DM. Compared with HV, patients with DM with obesity had 53 dysregulated miRNAs. Additionally, moving stepwise from HV to patients with obesity without DM to patients with obesity with DM, there was a consistent increase in expression levels of miR-23a-5p and miR-6087 and a consistent decrease in expressions levels of miR-6751-3p. Conclusions Our data show that the exosomal miRNAs is altered by dysregulated glucose metabolism in patients with obesity. This circulating exosomal miRNA signature in patients with obesity with or without DM is a potential biomarker and therapeutic target in these patients.
    Type of Medium: Online Resource
    ISSN: 2052-4897
    URL: Article
    DOI: 10.1136/bmjdrc-2020-001403
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2732918-5
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  • 6
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    Online Resource
    Iliopsoas plane block does not improve pain after primary total hip arthroplasty in the presence of multimodal analgesia: a single institution randomized controlled trial
    BMJ ; 2024
    In:  Regional Anesthesia & Pain Medicine
    Details
    In: Regional Anesthesia & Pain Medicine, BMJ
    Abstract: The clinical analgesic efficacy of iliopsoas plane block remains a subject of discussion. This study aimed to assess the analgesic efficacy of iliopsoas plane block under general anesthesia using multimodal analgesia. Methods Fifty-six adult patients who underwent elective primary hip arthroplasty were enrolled. Patients were randomized to receive either a single-shot iliopsoas plane block (10 mL 0.75% ropivacaine with 1:200 000 epinephrine) or a sham block (10 mL normal saline). All patients received general anesthesia, multimodal analgesia (preoperative buprenorphine patch, 5 µg/h), intraoperative intravenous dexamethasone (8 mg) and nefopam (20 mg), and round-the-clock acetaminophen and celecoxib. The primary outcome was the numeric rating scale pain score at rest 6 hour after surgery. Results Iliopsoas plane block did not have a notable advantage over the sham block in terms of pain relief at rest, as assessed by the numeric rating scale score, 6 hour after total hip arthroplasty (iliopsoas plane block: median, 4.0; IQR, 2.0–5.8; sham: median, 5.5; IQR, 2.3–6.8; median difference, −1.0; 95% CI −2.0 to 0.0; p≥0.999). Linear mixed model analysis showed no differences in pain scores, opioid consumption, quadriceps strength, or quality of recovery between the groups. Conclusions Iliopsoas plane block did not improve postoperative analgesia following total hip arthroplasty under general anesthesia with a multimodal analgesic regimen. The blockade of sensory femoral branches supplying the anterior hip capsule using iliopsoas plane block may not yield additional benefits concerning patient outcomes in the aforementioned clinical context. Trial registration number NCT05212038 , https://clinicaltrials.gov/ct2/show/NCT05212038
    Type of Medium: Online Resource
    ISSN: 1098-7339 , 1532-8651
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/rapm-2023-105092
    DOI: 10.1136/rapm-2023-105092.supp1
    DOI: 10.1136/rapm-2023-105092.supp2
    DOI: 10.1136/rapm-2023-105092.supp3
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2028901-7
    detail.hit.zdb_id: 1425299-5
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