Search

Objective: Given the existing evidence for the analgesic effect of acupuncture, the current study aimed to assess whether acupuncture could be feasible and manageable as an adjunctive therapy for cancer pain in a real-world hospital setting.Methods: Thirty patients in an Oncology department with moderate or severe pain were recruited and randomized to an adjunctive acupuncture group or control group, who received pharmacotherapy for pain management without acupuncture. The duration of the treatment course was 1 week with a 2-week follow-up. In total, four acupuncture sessions were administered, on days 1/2/4/6 of the trial. Pain intensity was measured using a numerical rating scale (NRS) and the daily opioid dose was recorded.Results: The overall trends favored acupuncture for both pain intensity and daily opioid consumption. The proportion of participants experiencing at least a 2-point reduction in the NRS at the end of the treatment was 93% (n = 14/15) for the acupuncture group and 57% (n = 8/14) for the control group (risk difference (RD) 36.1%, 95% confidence interval (CI) [7.4%–65.0%]; relative risk (RR) 1.63, 95% CI [1.02–2.62]; p = 0.04). There were no serious adverse events and no dropouts during the treatment.Conclusion: This pilot study showed that adding acupuncture to routine analgesia for patients with cancer pain was feasible and acceptable to patients. The clinical effects of adding acupuncture as an adjunctive therapy need to be further evaluated.Clinical trial registration number: ChiCTR1800017023 (Chinese Clinical Trial Registry)

IMPORTANCE: Research into acupuncture and acupressure and their application for cancer pain has been growing, but the findings have been inconsistent. OBJECTIVE: To evaluate the existing randomized clinical trials (RCTs) for evidence of the association of acupuncture and acupressure with reduction in cancer pain. DATA SOURCES: Three English-language databases (PubMed, Embase, and CINAHL) and 4 Chinese-language biomedical databases (Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang) were searched for RCTs published from database inception through March 31, 2019. STUDY SELECTION: Randomized clinical trials that compared acupuncture and acupressure with a sham control, analgesic therapy, or usual care for managing cancer pain were included. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. Random-effects modeling was used to calculate the effect sizes of included RCTs. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. MAIN OUTCOMES AND MEASURES: The primary outcome was pain intensity measured by the Brief Pain Inventory, Numerical Rating Scale, Visual Analog Scale, or Verbal Rating Scale. RESULTS: A total of 17 RCTs (with 1111 patients) were included in the systematic review, and data from 14 RCTs (with 920 patients) were used in the meta-analysis. Seven sham-controlled RCTs (35%) were notable for their high quality, being judged to have a low risk of bias for all of their domains, and showed that real (compared with sham) acupuncture was associated with reduced pain intensity (mean difference [MD], −1.38 points; 95% CI, −2.13 to −0.64 points; I2 = 81%). A favorable association was also seen when acupuncture and acupressure were combined with analgesic therapy in 6 RCTs for reducing pain intensity (MD, −1.44 points; 95% CI, −1.98 to −0.89; I2 = 92%) and in 2 RCTs for reducing opioid dose (MD, −30.00 mg morphine equivalent daily dose; 95% CI, −37.5 mg to −22.5 mg). The evidence grade was moderate because of the substantial heterogeneity among studies. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that acupuncture and/or acupressure was significantly associated with reduced cancer pain and decreased use of analgesics, although the evidence level was moderate. This finding suggests that more rigorous trials are needed to identify the association of acupuncture and acupressure with specific types of cancer pain and to integrate such evidence into clinical care to reduce opioid use.

Background Electroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed.Aim To examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy.Methods The study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis.Results and conclusions 32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30?min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice.

Background An ideal placebo design in clinical research should resemble the intervention under investigation to facilitate blinding, yet remain clinically inert. With regard to physical interventions such as acupuncture, a true placebo device has not been developed and validated. Since 1998, researchers have designed several placebo acupuncture devices (PADs). The three most widely used PADs are the Streitberger, the Park and the Takakura device.Aim This review focuses on evaluating studies of these devices, in the context of credibility of blinding (COB), assessment of penetrating pain or sensation, and de qisensation.Methods Electronic database searches were conducted in four English and two Chinese databases from their inception until November 2016. All studies included in the review were conducted on healthy participants and compared verum manual acupuncture with any of the aforementioned PADs with respect to one or more of the above three outcomes related to blinding effect.Results The synthesised analyses of the 15 included studies showed that the Streitberger and Park placebo devices may not blind participants successfully when tested at a sensitive acupuncture point (LI4). In terms of penetrating sensation, there were significant differences between these two placebo devices and verum acupuncture when applied at this point. The Takakura device was the only PAD that had the potential to blind the acupuncturist. However, the blinding analyses of all outcome measures were inconsistent.Conclusion Overall, there were insufficient data to confirm the blinding effects of these skin-contact PADs as each device was associated with limitations that warrant further design improvements.

BackgroundElectroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed.AimTo examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy.MethodsThe study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis.Results and conclusions32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30 min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice.

BackgroundAn ideal placebo design in clinical research should resemble the intervention under investigation to facilitate blinding, yet remain clinically inert. With regard to physical interventions such as acupuncture, a true placebo device has not been developed and validated. Since 1998, researchers have designed several placebo acupuncture devices (PADs). The three most widely used PADs are the Streitberger, the Park and the Takakura device.AimThis review focuses on evaluating studies of these devices, in the context of credibility of blinding (COB), assessment of penetrating pain or sensation, and de qisensation.MethodsElectronic database searches were conducted in four English and two Chinese databases from their inception until November 2016. All studies included in the review were conducted on healthy participants and compared verum manual acupuncture with any of the aforementioned PADs with respect to one or more of the above three outcomes related to blinding effect.ResultsThe synthesised analyses of the 15 included studies showed that the Streitberger and Park placebo devices may not blind participants successfully when tested at a sensitive acupuncture point (LI4). In terms of penetrating sensation, there were significant differences between these two placebo devices and verum acupuncture when applied at this point. The Takakura device was the only PAD that had the potential to blind the acupuncturist. However, the blinding analyses of all outcome measures were inconsistent.ConclusionOverall, there were insufficient data to confirm the blinding effects of these skin-contact PADs as each device was associated with limitations that warrant further design improvements.

Increasing placebo effect sizes over time have been reported in randomized controlled trials (RCTs) for outcomes related to psychiatric symptoms. The Neuropsychiatric Inventory (NPI) is a key outcome measure in clinical trials of the behavioral and psychological symptoms of dementia (BPSD). Accurate placebo effect size estimates for NPI are needed for sample size calculations in order to adequately power future studies. This study investigated variation in placebo effect sizes for NPI in RCTs testing oral interventions for BPSD. A search of PubMed was conducted in April 2016 for two-armed, double-blinded, placebo-controlled RCTs testing any oral intervention for management of BPSD using the NPI. Meta-analysis was conducted of baseline versus end of treatment placebo group data of included studies. Twenty-five RCTs published from 2000 to 2015 were included. Substantial variation in placebo effect sizes was detected. Participants in placebo groups showed greater improvements in recent studies compared with earlier studies. Subgroup analyses indicated robustness of this finding. From 2000 to 2008 there was no significant change in total NPI scores within placebo groups (12 studies; 1,056 participants), whereas from 2009 to 2015 there was significant improvement (mean difference: −2.68; 95% confidence interval: −4.38, −0.99; z = 3.10; p = 0.002, random effects; I2 = 76%; 13 studies; 1,170 participants). This increase in NPI effect sizes in placebo groups has important implications for power calculations for future clinical trials of BPSD. Effect size estimates for NPI need to be based on more recent studies.

Background Most popular single-use acupuncture needles consist of a stainless steel shaft with a handle made of copper coil or plastic stick.Objectives To determine the strengths and weaknesses of these two handle types for needle buckling.Methods The buckling load for acupuncture needles with these two different handle types was determined using a digital scale, and the stiffness of stainless steel wires used in different types of acupuncture needles was measured using a Dynamic Mechanical Analysis machine.Results This study showed that an acupuncture needle with a copper coil handle was far more susceptible to buckling than a needle with a plastic stick handle. The average buckling force of acupuncture needles with plastic stick handles was 46.7% higher than that with copper coil handles for needles of 0.25 mm×30 mm, and 30.8% higher for needles of 0.25 mm×60 mm. Replacing a copper coil handle with a plastic stick handle could save about 100 tonnes of copper wires and 20 million metres of medical grade stainless steel wire a year worldwide.Conclusions The results from this study suggest that the common practice of using coiled copper for handles on acupuncture needles should be re-evaluated. Replacing a copper coil handle with a plastic stick handle would significantly reduce needle buckling and improve patient comfort and safety. This would also reduce the consumption of copper and medical grade stainless steel wire considerably.

Objectives The present work examined the surface conditions and various other physical properties of sterilised single-use stainless steel acupuncture needles from two of the most popular brands widely used in many countries.Methods Scanning electron microscope (SEM) images were taken for 10 randomly chosen needles from each brand. Further SEM images were taken after each of these needles underwent a standard manipulation with an acupuncture needling practice gel. A comparison of forces and torques during the needling process was also carried out.Results The SEM images revealed significant surface irregularities and inconsistencies at the needle tips, especially for needles from one of the two brands. Metallic lumps and small, loosely attached pieces of material were observed on the surfaces of some needles. Some of the lumps and pieces of material seen on the needle surfaces disappeared after the acupuncture manipulation. If these needles had been used on patients, the metallic lumps and small pieces of material could have been deposited in human tissues, which could have caused adverse events such as dermatitis. Malformed needle tips might also cause other adverse effects including bleeding, haematoma/bruising, or strong pain during needling. An off-centre needle tip could result in the needle altering its direction during insertion and consequently failing to reach the intended acupuncture point or damaging adjacent tissues.Conclusions These findings highlight the need for improved quality control of acupuncture needles, with a view to further enhancing the safety and comfort of acupuncture users.

St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and the potential clinical impact.

Cytochrome P450 (CYP) 3A4 is the most abundant enzyme of CYPs in the liver and gut that metabolizes approximately 50% currently available drugs. A number of important drugs have been identified as substrates, inducers, and/or inhibitors of CYP3A4. The substrates of CYP3A4 considerably overlap with those of P-glycoprotein. Both CYP3A4 and P-glycoprotein are subject to inhibition and induction by a number of factors. Mechanism-based inhibition of CYP3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation occurring when some xenobiotics or drugs are converted by CYPs to reactive metabolites. Such an inhibition of CYP3A4 is caused by chemical modification of the heme, the protein, or both as a result of covalent binding of modified heme to the protein. To date, the identified clinically important mechanism-based CYP3A4 inhibitors mainly include macrolide antibiotics (eg, clarithromycin and erythromycin), anti-HIV agents (eg, ritonavir and delavirdine), antidepressants (eg, fluoxetine and fluvoxamine), calcium channel blockers (eg, verapamil and diltiazem), steroids and their modulators (eg, gestodene and mifepristone), and several herbal and dietary components. The inactivation of CYP3A4 by drugs often causes unfavorable and long-lasting drug-drug interactions and probably fatal toxicity, depending on many factors associated with the enzyme, drugs, and the patients. Clinicians are encouraged to have a sound knowledge of drug-induced, mechanism-based CYP3A4 inhibition; take proper cautions, and perform close monitoring for possible drug interactions when using drugs that are mechanism-based CYP3A4 inhibitors. To minimize drug-drug interactions involving mechanism-based CYP3A4 inhibition, it is necessary to choose safe drug combination regimens, adjust drug dosages appropriately, and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices.

The multidrug resistance associated proteins (MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8 and MRP9) belong to the ATP-binding cassette superfamily (ABCC family) of transporters. They are expressed differentially in the liver, kidney, intestine, brain and other tissues. These transporters are localized to the apical and/or basolateral membrane of the hepatocytes, enterocytes, renal proximal tubule cells and endothelial cells of the blood-brain barrier. Several MRPs (mainly MRP1-3) are associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. MRPs transport a structurally diverse array of important endogenous substances and xenobiotics and their metabolites (in particular conjugates) with different substrate specificity and transport kinetics. Most MRPs are subject to induction and inhibition by a variety of compounds. Several nuclear receptors, including pregnane X receptor (PXR), liver X receptor (LXR), and farnesoid receptor (FXR) participate in the regulation of MRPs. MRPs play an important role in the absorption, distribution and elimination of various drugs in the body and thus may affect their efficacy and toxicity and cause drug-drug interactions. MRPs located in the blood-brain barrier can restrict the penetration of compounds into the central nervous system. Mutation of MRP2 causes Dubin-Johnson syndrome, while mutations in MRP6 are responsible for pseudoxanthoma elasticum. More recently, mutations in mouse Mrp6/Abcc6 gene is associated with dystrophic cardiac calcification (DCC), a disease characterized by hydroxyapatite deposition in necrotic myocytes. A single nucleotide polymorphism, 538G A in the MRP8/ABCC11 gene, is responsible for determination of earwax type. A better understanding of the function and regulating mechanism of MRPs can help minimize and avoid drug toxicity, unfavourable drug-drug interactions, and to overcome drug resistance.

The pregnane X receptor (PXR/NR1I2) gene is a critical transcriptional regulator of a number of important drug metabolizing enzymes and transporters. This study was undertaken to determine the frequencies of single nucleotide polymorphisms (SNPs) and haplotypes and to detect yet unknown SNPs in the NR1I2 gene in 210 unrelated healthy Han Chinese in comparison with other ethnic groups. We also characterized the functional impact of two SNPs, -24622A T in the 5'-untranslated region and -24446C A in exon 1 of NR1I2, by constructing three recombinants and monitoring promoter activity using the dual luciferase reporter gene assay. Genomic DNA was isolated from peripheral leukocytes and subjected to polymerase chain reaction (PCR) amplification, followed by direct DNA sequencing. Sixteen SNPs in NR1I2 with frequencies of 0.3-90.3% were found in Han Chinese, two of which (-25439A G in the 5'-untranslated region and 7637C T in intron 5) are previously unknown. The mutant allelic frequencies varied from 0.3% to 90.3%. Most of the detected SNPs were located in introns. A total of 15 linkage disequilibriums were detected; and positive linkage disequilibriums were found between -24381A C in exon 1 and -24113G A in intron 1, and 252A G in intron 2 and 275A G in intron 2 (p2 = 1, P < 0.001). A total of 42 haplotypes were inferred and the two most frequent haplotypes were H1 (TCAGGGGCCACC) and H2 (CCGAAAACTAAT) with a frequency of 15.1%. The activity of the recombinants with alleles containing the -24622A T in the 5'-untranslated region or -24446C A in exon 1 was 30-40% higher than that in the wild-type (reference genotype). These results indicate that there are marked ethnic differences in the frequency between Han Chinese and other ethnic groups and that alleles with -24622A T in the 5'-untranslated region and - 24446C A in exon 1 of the NR1I2 gene result in an increased activity compared to the wild-type. Further studies are warranted to explore the clinical and toxicological impact of SNPs and haplotypes of NR1I2 in various ethnic groups.

In recent years, there has been a globally increasing application of herbal medicines and dietary supplements to treat various chronic diseases and to promote health. However, there are increasing clinical reports on the organ toxicities associated with consumption of herbal medicines. This review updates the knowledge on metabolic activation of herbal components and its clinical and toxicological implications. Like many synthetic drugs undergoing metabolic activation to form reactive metabolites which are often associated with drug toxicity, it is recognized that some herbal components may also be converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYPs) and less frequently by Phase II conjugating enzymes. This is exemplified by aristolochic acids (AAs) in Aristolochia spp, which undergo reduction of the nitro group by hepatic CYP1A1/2 or peroxidases in extrahepatic tissues to generate highly reactive cyclic nitrenium ions. The latter can react with macromolecules (DNA and protein), resulting in activation of Hras oncogene and gene mutation in renal cells and finally carcinogenesis of the kidneys. Some naturally occurring flavonoids (e.g. quercetin) and alkenylbenzenes (e.g. safrole, methyleugenol and estragole) can undergo metabolic activation by sequential 1-hydroxylation and sulfation, resulting in reactive intermediates capable of forming DNA adducts and finally genotoxicity. Additional examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming dietary supplements but caused severe hepatotoxicity. Extensive pulegone metabolism generated pcresol that was a glutathione depletory, whereas the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which can inactivate hepatic CYP3A and epoxide hydrolase through covalent binding. The hepatotoxic and carcinogenic species of plant pyrrolizidine alkaloids (e.g. echimidine and jacobine), namely pyrrole-type metabolites, are generated by hepatic CYP2B6 and CYP3A4. Potential mechanisms underlying the hepatotoxicity of kava have been related to intracellular glutathione depletion and/or quinone formation. Some herbal constituents (e.g. capsaicin from chili peppers, glabridin from licorice root, oleuropein in olive oil, dially sulfone in garlic, and resveratrol found in red wine) behave as mechanism-based inhibitors of various CYPs. This may provide an explanation for some reported herb-drug interactions. In addition, the inhibition of CYPs by herbal constituents may decrease the formation of toxic metabolites and thus inhibit carcinogenesis, as CYPs play an important role in procarcinogen activation. Due to the wide use and easy availability of herbal medicines, further research should be conducted to ensure the safety and quality of herbal medicine.

Seasonal allergic rhinitis (SAR) is a common condition with relatively high prevalence in Australia. It causes a significant impact on sufferers' quality of life (QoL). Meta-analysis has shown that the efficacy of acupuncture for SAR is uncertain.