Loss of effectiveness with an implanted drug delivery system for intrathecal pain therapy due to corrosion

Introduction

Intrathecal drug delivery is an established invasive treatment option. Most common complication is catheter malfunction, which can lead to overdose or withdrawal.

Case Presentation

A 61-year-old female patient underwent an elective replacement of an intrathecal drug delivery pump. The patient complained about a loss of effectiveness over the past 2 years. Intraoperatively, a white mass corresponding to morphine precipitation in the pump pocket was found, which appeared to be due to corrosion at the pump-catheter connection site.

Conclusions

Recommendations on how to deal with the decreasing effectiveness of intrathecal drug delivery and on intraoperative catheter handling are provided.     

超声药物透入联合针灸治疗腰椎间盘突出症临床研究

目的观察超声药物透入联合针灸治疗腰椎间盘突出症的临床疗效。 方法选取2019年l月至2021年5月就诊于北京市石景山医院骨科及中医科门诊的腰椎间盘突出症患者140例,采用随机数字表法分为治疗组和对照组,每组各70例。治疗组采用超声药物透入联合针灸治疗,每日1次,共治疗2周;对照组采用单纯针灸治疗,每日1次,共治疗2周。观察2组患者首次治疗前及治疗后2周采用视觉模拟评分法（VAS）及日本骨科协会评估治疗分数（JOA）评分,比较治疗效果。 结果治疗前2组VAS评分差异无统计学意义［治疗组：（7.46±0.54）分,对照组：（7.40±0.74）分,P＞0.05］,治疗后2组VAS评分［治疗组：（1.73±0.94）分,对照组：（2.75±1.14）分］均较治疗前下降（P＜0.05）,且治疗组明显低于对照组（P＜0.05）。治疗前2组JOA评分差异无统计学意义［治疗组：（14.25±3.86）分,对照组：（14.15±3.45）分,P＞0.05］,治疗后2组JOA评分［治疗组：（21.04±3.16）分,对照组：（18.88±3.32）分］均较治疗前升高（P＜0.05）,且治疗组明显高于对照组（P＜0.05）。与对照组相比,治疗组患者总有效率明显提高（97.14% vs 82.86%）,差异有统计学意义（P＜0.05）。 结论超声药物透入联合针灸治疗腰椎间盘突出症能明显提高临床治疗效果。     

The effectiveness of acupuncture in the treatment of Gulf War Illness

IntroductionIt can be challenging to study complex and novel health states within the parameters of a RCT. This report describes the use of an unblinded Phase II Clinical Trial design to investigate the effectiveness of acupuncture in the treatment of Gulf War Illness (GWI). GWI is a complex illness found among veterans of the first Gulf War, and is characterized by multiple symptoms, including fatigue, sleep and mood disturbances, cognitive dysfunction, and musculoskeletal pain. No published trials of acupuncture for the treatment of GWI exist. This trial is designed to both answer questions of the effectiveness of acupuncture for our entire sample, as well as subgroups with of individual presentations of GWI.Materials and methodsOur primary outcome is quality of life as measured by the SF-36. In an effort to better understand this complex disease and its treatment, our multi-level measurement plan examines psychosocial variables, fatigue, sleep quality, pain, and biomarkers of inflammation and immune status. All of the measurement instruments used in this trial show good validity and reliability.ResultsThis study is ongoing and clinical results are not available. We have achieved good feasibility of our recruitment, treatment, and data collection procedures.ConclusionsLow constraint RCT designs are an appropriate choice when investigating conditions in which the causes and mechanisms of disease are poorly understood. This naturalistic RCT includes individualized protocols, a clinically supported length and dose of treatment, a wait list control arm, and the ethical benefit that all subjects receive treatment during the study.     

针灸治疗膝骨关节炎的应用效果及机制*

背景：研究表明针灸结合中药治疗膝骨关节炎具有一定的效果。目的：探讨针灸结合中药治疗膝骨关节炎的机制及效果评价。方法：建立膝骨关节炎动物模型,检测相关因子基质金属蛋白酶3、转化生长因子β、白细胞介素1β和肿瘤坏死因子α表达含量的变化;对应用针灸联合药物治疗膝骨关节炎的患者进行随访观察,针刺主穴结合配穴,中药服用或外敷熏蒸,观察膝关节活动功能恢复情况,明确应用针灸结合中药干预治疗的效果。结果与结论：针灸治疗能够通过降低基质金属蛋白酶3、转化生长因子β、白细胞介素1β和肿瘤坏死因子α的含量,延缓膝关节软骨的破坏,改善膝关节功能,从而发挥对膝骨性关节炎的治疗作用。膝骨关节炎的患者应用针灸结合中药治疗后,获得较好的效果,治疗有效率高达90%以上,并且与单一应用透明质酸钠或针灸治疗相比较,针灸结合中药治疗的有效率更高,治疗效果更好。     

The effectiveness and safety of acupuncture treatment on sciatica: A systematic review and meta-analysis

BackgroundSciatica results from primary or secondary damage to the sciatic nerve in the lumbar or gluteal region. The first option for sciatica is analgesics, but their therapeutic effect and safety in long-term use are questionable. On the other hand, acupuncture has recently been recognized as a complementary and alternative medicine (CAM) to conventional medicine, and studies on its effectiveness and safety have been actively conducted.ObjectiveTo systematically compare acupuncture with analgesics in terms of effect, safety, and durability in the treatment of sciaticaMethodsThis review was performed in accordance with Cochrane Handbook for Systematic Reviews of Interventions Version 6.2. Four databases were searched for this review: Wangfang, the Korean Traditional Knowledge Portal (KTKP), PubMed, and EBSCOhost. The primary outcome measures in the review were total effective rate (TER), visual analog scale (VAS) score and pain threshold, and the secondary ones were adverse effects (AEs) and relapse rates. Risk ratio (RR) for TER and mean difference (MD) for VAS score and pain threshold were used as statistics for the meta-analysis of effectiveness, along with associated 95 % confidence intervals (CIs) and P-values. AEs and relapse rates were used for the safety and durability of the interventions. Version 2 of the Cochrane risk-of-bias assessment tool for randomized trials (RoB 2) was used for the methodological quality of randomized controlled trials (RCTs) included in the review.ResultsThe synthesized TER of 28 RCTs involving 2707 participants was significantly higher in the acupuncture group compared to the analgesic group (RR [95 % CI] = 1.20 [1.16, 1.24], P < 0.001). The synthesized VAS score of 7 RCTs involving 589 participants was significantly reduced in the acupuncture group compared to the analgesic group (MD [95 % CI] = − 1.78 [− 2.44, − 1.12], P < 0.001). In 5 RCTs involving 311 participants, the synthesized pain threshold was significantly elevated in the acupuncture group compared to the analgesic group (MD [95 % CI] = 0.93 [0.64, 1.22], P < 0.001). Additionally, adverse effects (AEs) and relapse rates of RCTs in the review were lower in the acupuncture group compared to the analgesic group.ConclusionIn this systematic review, acupuncture treatment was significantly effective and safe compared to analgesics in sciatica. In the future, studies with a rigorous study design are required to increase the validity of the effectiveness and safety of acupuncture treatment for sciatica.     

New drug combinations for the treatment of murine AIDS and macrophage protection

The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macrophages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of the lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) encapsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus GSH-loaded erythrocytes given with AZT (treatment A + L-RBC). Fludarabine was administered intraperitoneally, AZT in the drinking water and GSH was encapsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. The results obtained show that GSH-loaded erythrocytes provide additive effects in all the parameters examined. Alternation of a lympholitic drug and antiretroviral drug is effective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting different infectable cell compartments are better than treatments protecting mainly lymphocytes.     

针刺结合肌肉能量技术治疗前斜角肌综合征的疗效观察

目的:观察针刺肌筋膜触发点结合肌肉能量技术治疗前斜角肌综合征的疗效。方法:将60例受试者随机分为针刺组和结合组,每组各30例。针刺组给予针刺肌筋膜触发点治疗,结合组采用针刺肌筋膜触发点结合肌肉能量技术(MET)治疗。治疗前后分别用McGill疼痛问卷简表(SF-MPQ)评定,并评价临床疗效。结果:2组患者治疗20d后及治疗后3个月随诊,SF-MPQ均较治疗前明显下降(均P0.05),且结合组更低于针刺组(P0.05)。治疗后,结合组总有效率明显高于针刺组(P0.05)。3个月后复发率比较结合组明显低于针刺组(P0.05)。结论:对前斜角肌及周围相关肌进行针刺结合肌肉能量技术可以改善前斜角肌综合征引起的颈、肩、上肢的疼痛或麻木。     

川崎病治疗新进展及可能的机制

川崎病主要发生于5岁以下儿童的血管炎性疾病。本病的预后取决于冠状动脉损害的程度。经标准治疗(免疫球蛋白冲击联合阿司匹林),大部分患儿可取得良好的治疗效果,但仍有部分患儿表现为静脉注射免疫球蛋白(IVIG)抵抗,近年来随着对川崎病发病机制及病因的研究,一些新的治疗方法不断出现,包括英夫利昔单抗、甲氨蝶呤、环磷酰胺、阿那白滞素、血浆置换等。本文将介绍川崎病治疗的新进展及可能的机制。     

Differences in client and therapist views of the working alliance in drug treatment

Background: There is growing evidence that the therapeutic alliance is one of the most consistent predictors of retention and outcomes in drug treatment. Recent psychotherapy research has indicated that there is a lack of agreement between client, therapist and observer ratings of the therapeutic alliance; however, the clinical implications of this lack of consensus have not been explored.

Aims: The aims of the study are to (1) explore the extent to which, in drug treatment, clients and counsellors agree in their perceptions of their alliance, and (2) investigate whether the degree of disagreement between clients and counsellors is related to retention in treatment.

Methods: The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Client and counsellor ratings of the therapeutic alliance (using the WAI‐S) were obtained during weeks 1–12. Retention was in this study defined as remaining in treatment for at least 12 weeks.

Results: Client and counsellor ratings of the alliance were only weakly related (correlations ranging from r = 0.07 to 0.42) and tended to become more dissimilar over the first 12 weeks in treatment. However, whether or not clients and counsellors agreed on the quality of their relationship did not influence whether clients were retained in treatment.

Conclusions: The low consensus between client and counsellor views of the alliance found in this and other studies highlights the need for drug counsellors to attend closely to their clients' perceptions of the alliance and to seek regular feedback from clients regarding their feelings about their therapeutic relationship.     

Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein

Transporter proteins such as P-glycoprotein are major determinants of intracellular drug concentrations. Moreover, inhibition or induction of transporters is an important mechanism underlying drug interactions in humans. However, very little is known whether beta-adrenoceptor antagonists are substrates and/or inhibitors of P-glycoprotein. Therefore, we investigated the P-glycoprotein-mediated transport of propranolol, metoprolol, bisoprolol, carvedilol and sotalol in P-glycoprotein-expressing Caco-2 monolayers and inhibition of P-glycoprotein-mediated digoxin transport by the beta-adrenoceptor antagonists. A significant inhibition of polarized, basal to apical drug transport by the P-glycoprotein inhibitor PSC-833 was observed for bisoprolol (0.5 and 5 microm) and carvedilol (0.5 microm). Moreover, propranolol and carvedilol inhibited P-glycoprotein-mediated digoxin transport with IC(50) values of 24.8 and 0.16 microm, respectively, whereas metoprolol and sotalol had no effect. Bisoprolol significantly inhibited directional digoxin transport at 50 and 250 microm by 31% and 44%, respectively. Taken together, P-glycoprotein is likely to be one determinant of bisoprolol and carvedilol disposition in humans. In addition, the beta-adrenoceptor antagonists propranolol and carvedilol significantly inhibit P-glycoprotein function thereby possibly contributing to drug interactions in humans (e.g. digoxin-carvedilol and cyclosporine-carvedilol).     

A morphine-triggered delivery system useful in the treatment of heroin addiction

The ultimate objective of this work is to develop a device that can be triggered by morphine to release naltrexone. Two device configurations are described. In one configuration, naltrexone is dispersed in cellulose acetate phthalate microspheres which are then spray-coated with trilaurin. In the other configuration, naltrexone is dispersed in an n-octyl half ester of methyl vinyl ether and maleic anhydride copolymer and the mixture fabricated into a disk which is then coated with trilaurin. The microspheres are designed to release naltrexone abruptly while the disks are designed to release naltrexone at a constant rate over a two week period. The microspheres, or the disk along with a reversibly inactivated lipase are placed inside a semipermeable membrane that allows free passage of morphine and naltrexone but excludes the higher molecular weight components of the device. Reversible inactivation of lipase is achieved by covalent attachment of morphine and complexing with morphine antibody. Activation of the device occurs by diffusion of morphine into the device and displacing the lipase-morphine conjugate from the antibody. The activated lipase then removes the trilaurin protective coating, thus triggering naltrexone release.     

The effectiveness of the controlled release of simvastatin from β‐TCP macrosphere in the treatment of OVX mice

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side‐effects. Given the associated side‐effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta‐tricalcium phosphate (β‐TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β‐TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the r elease of simvastatin, an apatite coating was made around the β‐TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β‐TCP, β‐TCP with simvastatin, apatite‐coated β‐TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non‐implanted side (left) and showed that β‐TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite‐coated β‐TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation. Copyright © 2013 John Wiley & Sons, Ltd.     

药物与视神经管减压治疗急性球后视神经炎疗效观察

目的探讨药物与视神经管减压手术治疗急性球后视神经炎疗效。方法回顾1988～2005年收治双眼急性球后视神经炎54例108眼,经药物治疗与视神经管减压手术治疗（以下简称减压治疗）并观察其疗效。结果54例108眼经药物治疗16～20d有46例（85．19％）95眼（87．96％）视力恢复到0．5—1．2,但仍有8例（14．81％）13眼（12．04％）视力无光感～2m数指。选择视力最差的无光感～30cm数指的8例8眼施行减压治疗,术后药物继续治疗16～20d,术后8眼视力恢复到0．3～0．7。经3年观察,术侧眼视力0．5～1．0,眼底视乳头色正常;而未手术侧的5眼视力光感-20cm数指,眼底视乳头苍白,血管细小,呈鲜明对比,疗效迥然不同。结论①球后视神经炎经药物治疗,大多数病例视力恢复较好。②经药物治疗2—3周少数病例视力仍无光感一眼前指数,视乳头淡白,经CT或MRI检查排除颅内病变,而球后视神经明显增粗的重症病例,应行减压治疗,可恢复较好视力。     

A retrospective drug utilization evaluation of vancomycin usage in paediatric patients

Objective: To evaluate the appropriateness of use of vancomycin in paediatric patients at KK Women's and Children's Hospital, the major paediatric hospital in Singapore to identify potential problems in prescribing practices that may necessitate intervention to optimize vancomycin usage. Methods: A retrospective drug utilization evaluation was performed for paediatric patients who received intravenous vancomycin from 1 June 1998 to 31 June 1999. The outcome measures were consistency of vancomycin indication with recommended guidelines, dosing regimens, microbiological data, monitoring of serum drug levels, renal function, clinical outcomes and adverse drug reactions (ADRs). Results: A total of 96 cases was available for evaluation. Sixty‐two (64·6%) courses of vancomycin were consistent with guidelines for indication of therapy. Eighty‐six (89·6%) of the dosing regimen were consistent. All infusion times that were recorded (56·3%) were consistent with criteria. Of the patients treated with vancomycin for more than 1 day, peak and/or trough serum vancomycin levels were ordered for 70 cases. Of the 56 cases with paired levels ordered, 46 cases had at least one level that fell outside the therapeutic range. Nineteen (19·8%) cases of ADRs were documented. Fifty‐eight (60·4%) cases received concurrent nephrotoxic drugs. However, a substantial portion of vancomycin courses were apparently not prescribed for appropriate indications, and there was poor recording of vancomycin administration information and sampling time. Conclusion: The majority of dosing regimens of vancomycin was consistent with guideline criteria. The most evident problem was the sub‐optimal use of the monitoring of vancomycin serum levels. The information derived from this study may be used as a for further study and for the development of strategies for optimize vancomycin usage.     

针灸治疗急性脑梗死临床疗效的Meta分析

目的 采Meta分析软件分析针灸对急性脑梗死患者的美国国立卫生研究院脑卒中量表(NIHSS)评分及有效率的影响,从而评价针灸对脑梗死的临床疗效。 方法 检索并选取公开发表的关于针灸治疗急性脑梗死的临床随机对照试验文献,对符合纳入标准的,采用Rev Man5.3版统计学软件进行统计学分析。 结果 本研究共纳入研究39项,患者3792例,经Meta分析发现,神经功能缺损评分MD=-1.86,其95%可信区间为-2.06~-1.66,差异有统计学意义（P<0.01）,结果表明,针灸结合西医常规综合疗法对急性脑梗死患者神经功能缺损的改善效果优于西医常规综合疗法;有效率Meta分析结果,疗效合并效应量OR=3.95,其95%可信区间为3.02~5.16,差异有统计学意义（P<0.01）,结果表明,针灸结合常规西医综合疗法治疗急性脑梗死的有效率优于西医常规综合治疗;显效+痊愈率Meta分析结果为,疗效合并效应量OR=1.54,其95%可信区间为1.40~1.70,差异有统计学意义（P<0.01）,结果表明,针灸结合常规西医综合疗法治疗急性脑梗死的显效+痊愈率优于西医常规综合疗法。 结论 针灸治疗急性脑梗死有效。     

The new drug combinations: their place in the treatment of uncomplicated Plasmodium falciparum malaria

Malaria is a leading cause of morbidity and mortality in developing countries. Selection of mutant Plasmodium falciparum malaria strains under drug pressure has led to the development of drug resistance. There is a pressing need for effective, safe, practicable drug combinations that hve lower selection pressure. A review of the mein drug combinations, which are recently registered or are still under development, was undertaken, with special attention to the atovaquone-proguanil and artemether-lumefantrine combination.     

Finding new drug targets for the treatment of migraine attacks

No new preventive drugs specific to migraine have appeared for the last 20 years and existing acute therapies need improvement. Unfortunately, no animal models can predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signalling molecules can be tested in a human model. This model has predicted efficacy of nitric oxide synthase inhibition and calcitonin gene-related peptide receptor blockade. The pharmaceutical industry should pay more attention to human models, although methods are different from normal target validation.