Dexmedetomidine impairs success of patient-controlled sedation in alcoholics during ERCP: a randomized, double-blind, placebo-controlled study

Background

There is a lack of studies about procedural sedation of alcoholics. Dexmedetomidine is recommended for procedural sedation and reported effective for alcohol withdrawal. We evaluated the suitability of dexmedetomidine for sedation of alcoholics during endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Fifty patients with chronic alcoholism scheduled for elective ERCP were randomized 1:1 to receive dexmedetomidine (Dex group) (loading dose 1 μg kg^?1 over 10 min, followed by constant intravenous infusion 0.7 μg kg^?1 h^?1) or saline placebo (P group). Patient-controlled sedation with propofol–alfentanil was used by patients as a rescue method. Sedation was considered as successful if no intervention of an anesthesiologist was needed. Consumption of sedatives was registered, and sedation levels and vital signs were monitored.

Results

Dexmedetomidine alone was insufficient in all patients. The mean ± SD consumption of propofol was 159 ± 72 mg in the P group, and 116 ± 61 mg in the Dex group (p = 0.028). Sedation was successful in 19 of 25 (76 %) patients in the Dex group and in all patients in the P group (p = 0.022). The incidence of sedation adverse events did not differ between the groups. Dexmedetomidine was associated with delayed recovery.

Conclusions

Patient-controlled sedation with propofol and alfentanil but not dexmedetomidine can be recommended for sedation of alcoholics during ERCP.     

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention

Background

The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS).

Objective

We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI.

Methods

We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥ 50%.

Results

One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17 ± 14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6–22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index < 16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p = 0.9).

Conclusion

In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index < 16%.     

Immediate and short‐term effects of contextual priming on word retrieval in aphasia

Background: Many therapy techniques for word retrieval disorders use some form of priming to improve access to words. Priming can facilitate or interfere with naming under different circumstances. We examined effects of priming when combined with semantic or phonological context (training words in groups that are semantically or phonologically related) and how these effects interact with the type of naming impairment (semantically or phonologically based). Aims: We addressed three questions (1) Are word retrieval impairments differentially sensitive to priming with semantic or phonological contexts? (2) Would such differences be systematically related to deficits of semantic versus phonological processing? (3) Do effects of priming evolve from immediate interference to short‐term facilitation, as predicted by an interactive activation model of word retrieval? Methods & Procedures: A total of 11 chronic English‐speaking aphasic subjects with varied types of aphasia participated in this experiment. Background measures of semantic and phonological processing ability were administered to determine the nature of each subject's naming impairment. The experiment involved one‐session facilitation treatments for each of three context conditions (semantic, phonological, and unrelated), plus three replications (nine subjects) or one replication (two subjects). Ten pictures in each condition were tested before and after treatment. Five pictures were trained and five served as controls. Participants repeated the name of each picture four times (repetition priming) and then attempted to name each picture individually (naming probe). Repetition priming and naming probes were repeated eight times. We used McNemar tests to compare rates of correct responses before and after priming, and chi square analyses of correct responses and contextual errors on naming probes obtained during the priming sessions. Outcome & results: Our predictions were borne out in the data. Participants varied in their sensitivity to the semantic and phonological contexts. The error data suggest that interference during training is more likely when the context (semantic or phonological) and underlying source of the word processing impairment (semantic or phonological) match. Additionally, we found two sequential effects of contextual priming: immediate interference followed short‐term facilitation. Conclusions: These data have theoretical implications regarding the time course of priming effects, but also have important clinical implications. The present contextual priming procedure is relatively short and could be used as a predictor of performance patterns in a long‐term treatment protocol that uses this approach or other tasks that employ priming.     

Long-term maintenance of novel vocabulary in persons with chronic aphasia

Background: The study of novel word learning in aphasia can shed light on the functionality of patients' learning mechanisms and potentially help in treatment planning. Previous studies have indicated that persons with aphasia are able to learn some new vocabulary. However, these learning outcomes appear short-lived and evidence for the ability to use the newly learned words in the long term is lacking.

Aims: Participants with aphasia and matched controls underwent short training where they were taught to name novel objects with novel names. We studied the participants' word learning and particularly their long-term maintenance. We also examined whether the language and verbal short-term memory impairments of the participants with aphasia related to their ability to acquire and maintain phonological and semantic information on novel words.

Methods & Procedures: Two participants with nonfluent aphasia, LL and AR, and two matched controls took part in the experiment. They were taught to name 20 unfamiliar objects by repeating the names in the presence of the object picture. Half of the items carried a definition that was used to probe incidental semantic learning. There were four training sessions, a post-training test, and follow-up tests up to 6 months post-training. Learning measures included recognition of the trained objects, as well as spontaneous and cued recall in visual confrontation naming. Incidental semantic learning was measured by spontaneous recall of the definitions.

Outcomes & Results: Combining spontaneous and phonologically cued responses, LL acquired 70% and AR 55% of the novel words. With phonological cueing, LL named 50% of the items correctly up to 6 months post-training (vs 95–100% for the controls) and AR 25% up to 8 weeks post-training. AR's lexical-semantic processing, pseudoword repetition and verbal short-term capacity were inferior to those of LL. In line with this, AR learned fewer words and showed more decline in recognition memory for the trained items, and weaker recall of the semantic definitions.

Conclusions: Our results support previous findings that people with aphasia can learn to name novel items. More importantly, the results show for the first time that, with phonological cueing, an individual with aphasia can maintain some of this learning up to 6 months post-training. Moreover the results provide further evidence for the significance of the functional status of lexical-semantic processing on word learning success.     

Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment

BACKGROUND: Banking of testicular tissue from pre-pubertal boys before gonadotoxic treatment is a crucial step in fertility preservation. We wanted to find optimal methods for cryopreservation of testicular tissue from pre-pubertal boys, modifying techniques developed for fetal and adult human testicular tissue cryopreservation. METHODS: Testicular tissue was collected from five pre-pubertal boys undergoing gonadotoxic treatment in a clinical programme. Two freezing protocols, originally developed for fetal and adult human testicular tissue, were applied for pre-pubertal testicular tissue cryopreservation. In both methods, 5% dimethyl sulphoxide (DMSO) was used as a cryoprotectant. The integrity of the tissue was investigated in non-frozen tissue cultured for 24 h and in cryopreserved-thawed tissue, using two different programmes. We also analysed frozen-thawed samples cultured for 24 h in comparison with untreated fresh fixed control tissue. Immunohistochemical analysis using anti-MAGE-A4, vimentin and CD34 monoclonal antibodies was performed in order to visualize and characterize the cryodamage of the different testicular cells and compartments. The structure of the tissue was evaluated using light microscopy. Qualitative control analysis was performed using transmission electron microscopy. RESULTS: No clear structural changes were observed in the fresh, fresh cultured and cryopreserved testicular tissue after using the protocol developed for adult testicular tissue. The programme earlier successfully used for human fetal testicular tissue cryopreservation caused more tissue damage. CONCLUSIONS: Pre-pubertal testicular tissue from boys facing gonadotoxic treatment survives cryopreservation, can be cryobanked and hopefully used for fertility preservation. Slow programmed freezing with DMSO as a cryoprotectant is efficient in maintaining the spermatogonia, Sertoli cells and stromal compartment during freezing, thawing and tissue culture.     

国际医学杂志编辑委员会关于临床试验注册的声明

无私和信任是人体试验研究的核心。自愿参加研究的受试者是无私的,因为他们相信自己的参与将为他人健康的改善做出贡献,也相信研究者会尽最大努力减少受试者的风险。由于受试者的无私和信任,临床研究才成为可能,因此研究机构有义务使临床研究的实施符合伦理学要求,并诚实地报道研究结果。而诚实的报道首先需要知道所有现存的临床研究,即使其结果对赞助方不利。