Needles

We describe an approach to manipulate and measure mechanical interactions between cells and their underlying substrates by using microfabricated arrays of elastomeric, microneedle-like posts. By controlling the geometry of the posts, we varied the compliance of the substrate while holding other surface properties constant. Cells attached to, spread across, and deflected multiple posts. The deflections of the posts occurred independently of neighboring posts and, therefore, directly reported the subcellular distribution of traction forces. We report two classes of force-supporting adhesions that exhibit distinct force-size relationships. Force increased with size of adhesions for adhesions larger than 1 m 2 , whereas no such correlation existed for smaller adhesions. By controlling cell adhesion on these micromechanical sensors, we showed that cell morphology regulates the magnitude of traction force generated by cells. Cells that were prevented from spreading and flattening against the substrate did not contract in response to stimulation by serum or lysophosphatidic acid, whereas spread cells did. Contractility in the unspread cells was rescued by expression of constitutively active RhoA. Together, these findings demonstrate a coordination of biochemical and mechanical signals to regulate cell adhesion and mechanics, and they introduce the use of arrays of mechanically isolated sensors to manipulate and measure the mechanical interactions of cells.

The purpose of this study was to design and fabricate arrays of solid microneedles and insert them into the skin of diabetic hairless rats for transdermal delivery of insulin to lower blood glucose level. Methods. Arrays containing 105 microneedles were laser-cut from stainless steel metal sheets and inserted into the skin of anesthetized hairless rats with streptozotocin-induced diabetes. During and after microneedle treatment, an insulin solution (100 or 500 U/ml) was placed in contact with the skin for 4 h. Microneedles were removed 10 s, 10 min, or 4 h after initiating transdermal insulin delivery. Blood glucose levels were measured electrochemically every 30 min. Plasma insulin concentration was determined by radioimmunoassay at the end of most experiments. Results. Arrays of microneedles were fabricated and demonstrated to insert fully into hairless rat skin in vivo. Microneedles increased skin permeability to insulin, which rapidly and steadily reduced blood glucose levels to an extent similar to 0.05-0.5 U insulin injected subcutaneously. Plasma insulin concentrations were directly measured to be 0.5-7.4 ng/ml. Higher donor solution insulin concentration, shorter insertion time, and fewer repeated insertions resulted in larger drops in blood glucose level and larger plasma insulin concentrations. Conclusions. Solid metal microneedles are capable of increasing transdermal insulin delivery and lowering blood glucose levels by as much as 80% in diabetic hairless rats in vivo.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype B predominates in Brazil, but in the southern region subtype C is the most frequent, followed by subtypes B, F1 and recombinant forms. In southern Brazil, these subtypes co-circulate in subjects with homogeneous demographic and clinical features, enabling a better understanding of the role of HIV-1 subtypes on the characteristics of infection. Objectives: To evaluate the prevalence of different HIV-1 subtypes in subjects with recent diagnosis for HIV infection in the extreme south of Brazil, and to study their association with demographic, behavioral, clinical and laboratorial characteristics. Study design: We have determined the genetic sequence of viral protease and reverse transcriptase (polymerase, connection and RNase H domains) isolated from studied subjects. Viral subtype was inferred by comparison with reference HIV sequences, and recombination was determined with Simplot analysis. The association of HIV-1 subtypes with studied characteristics was evaluated by chi-square, Fisher's exact, Student's t and Kruskal-Wallis tests. Results: Two hundred and forty-five HIV isolates were molecularly characterized, and the association with variables was studied for 233 (95.1%) patients. Of those, 46.8% followed AIDS defining criteria. HIV-1C was responsible for 56.3% of infections, and was associated with heterosexual transmission (p = 0.001) and with higher CD4 + T-cell counts (p = 0.02). Conclusions: The molecular epidemiology of HIV-1 in the southernmost Brazil is currently steady with predominance of HIV-1C. This is the first study showing a robust association of the infection by this subtype and heterosexual transmission in the state of Rio Grande do Sul, Brazil.

Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN.

Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been investigated have had low molecular weights due to the limited permeability of the skin barrier. This barrier resides in the outermost skin layer, the stratum corneum. It is mechanical, anatomical, as well as chemical in nature: laterally overlapping cell multi-layers are sealed by tightly packed, intercellular, lipid multi-lamellae. Chemical skin permeation enhancers increase the transport across the barrier by partly solubilising or extracting the skin lipids and by creating hydrophobic pores. This is often irritating and not always welltolerated. The TTS approach allows drugs (< 400 Da in size) to permeate through the resulting pores in the skin, with a short lag-time and subsequent steady-state period. Drug bioavailability for TTS delivery is typically below 50% without the first pass effect. Wider, hydrophilic channels can be generated by skin poration with the aid of a small electrical current (≤ 0.4 mA/cm 2) across the skin (iontophoresis) or therapeutic ultrasound (few W/cm 2 ; sonoporation). High-voltage (> 150 V; electroporation) widens the pores even more, and often irreversibly. These standard poration methods require experience and equipment and are not practical; at best, charged/small molecules (≤ 4 kDa in size) can thus be delivered efficiently across the skin. In spite of the potential harm of gadget-driven skin poration, this method is used to transport molecules that conventional TTS patches are unable to deliver, especially polypeptides. Lipid-based drug carriers (liposomes, niosomes, nanoparticle microemulsions, etc.) were proposed as alternative, low-risk delivery vehicles. Such suspensions provide an improved drug reservoir on the skin, but the aggregates remain confined to the surface. Conventional carrier suspensions can also increase skin hydration and/or behave as skin permeation enhancers. In contrast, the recently developed, highly deformable carriers, Transferomes, comprise pharmaceutically-acceptable, established compounds and are thought to penetrate the skin barrier along the naturally occurring transcutaneous moisture gradient. Transfersomes are believed to penetrate the hydrophilic (virtual) channels in the skin, which they track and widen after non-occlusive administration. Both small and large hydrophobic and hydrophilic

Objectives. We sought to investigate the acute hemodynamic effects of graded balloon dilation atrial septostomy (BDAS) and to define the long-term impact of this procedure on New York Heart Association functional class and survival in adult patients with primary pulmonary hypertension (PPH).

For clinical trials of acupuncture, it would be desirable to have a sham procedure that is indistinguishable from the real treatment, yet inactive. A sham needle has been designed which telescopes instead of penetrating the skin. The Park Sham Device involves an improved method of supporting the sham needle and requires validation. The objective of these studies was to test whether the sham procedure using the new device was 1) indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and 2) inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. The studies were designed as subject and assessor blind, randomised controlled trials. Study 1) included 58 patients enrolled in a clinical trial of acupuncture for acute stroke. Study 2) included 63 healthy, acupuncture naïve, adult volunteers. The interventions used were real or sham acupuncture using the Park Sham Device. Study 1) was set in a district general hospital, and study 2) in a university laboratory. The outcome measure in study 1) was the form of treatment that patients believed they had received. In study 2) the outcome measure was experience of de qi, as judged by three acupuncture experts. No patient in either group(study 1) believed he or she had been treated with the sham needle. In 40 volunteers (study 2) for whom experts achieved consensus, the relative risk of experiencing de qi with real acupuncture to that with sham acupuncture was 15.38 (95% CI 2.26 to 104.86). The inter-rater reliability of all 13 experts (study 2), calculated from their judgements on 10 subjects selected by randomisation, was 0.52 (95% CI 0.19 to 0.61). In conclusion, the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and is inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. It is therefore a valid control for acupuncture trials. The findings also lend support to the existence of de qi, a major concept underlying traditional Chinese acupuncture.

This study examined the effect of vapor lock on canal debridement efficacy by testing the null hypothesis that there is no difference between a &quot;closed&quot; and an &quot;open&quot; system design in smear layer and debris removal by using a side-vented needle for irrigant delivery. Roots in the closed system were sealed with hot glue and embedded in polyvinylsiloxane to restrict fluid flow through the apical foramen during cleaning and shaping. For the open system, the apical foramen was enlarged and connected to the external environment via a channel within the polyvinylsiloxane to permit unrestricted fluid flow. Smear and debris scores were evaluated by using scanning electron microscopy and analyzed by using Cochran-Mantel-Haenszel statistic. No difference in smear scores was detected between the 2 systems at all canal levels. Significant differences in debris scores between the 2 systems were found at each canal level: coronal (P &lt; .001), middle (P &lt; .001), and apical...

Ultrasound-guided needle placement is widely used in the clinical setting, particularly for central venous catheter placement, tissue biopsy and regional anesthesia. Difficulties with ultrasound guidance in these areas often result from steep needle insertion angles and spatial offsets between the imaging plane and the needle. Acoustic Radiation Force Impulse (ARFI) imaging leads to improved needle visualization because it uses a standard diagnostic scanner to perform radiation force based elasticity imaging, creating a displacement map that displays tissue stiffness variations. The needle visualization in ARFI images is independent of needle-insertion angle and also extends needle visibility out of plane. Although ARFI images portray needles well, they often do not contain the usual B-mode landmarks. Therefore, a three-step segmentation algorithm has been developed to identify a needle in an ARFI image and overlay the needle prediction on a coregistered B-mode image. The steps are: (1) contrast enhancement by median filtration and Laplacian operator filtration, (2) noise suppression through displacement estimate correlation coefficient thresholding and (3) smoothing by removal of outliers and best-fit line prediction. The algorithm was applied to data sets from horizontal 18, 21 and 25 gauge needles between 0-4 mm offset in elevation from the transducer imaging plane and to 18G needles on the transducer axis (in plane) between 10° and 35° from the horizontal. Needle tips were visualized within 2 mm of their actual position for both horizontal needle orientations up to 1.5 mm off set in elevation from the transducer imaging plane and on-axis angled needles between 10°-35° above the horizontal orientation. We conclude that segmented ARFI images overlaid on matched B-mode images hold promise for improved needle visibility in many clinical applications.

from the V-P shunt, the imaging was adequate and instrumental in avoiding the shunt during needle placement. There are reports in the literature of ultrasound guidance being used when nerve stimulator-guided peripheral nerve blocks were contraindicated, or simply were not feasible. 3,4 There has also been reported 1 case of a patient receiving a nerve stimulator-guided supraclavicular block with a history of bilateral deep brain stimulators for the treatment of Parkinson's disease. 5 However, there are no reports of ultrasound-guided interscalene block in a patient with a V-P shunt.

Nerve injury can arise as a complication of peripheral nerve block anesthesia. Of the various factors involved, the trauma caused by the injection needle may be of significance. In this experimental study the frequency of fascicular injury was investigated immediately after needling isolated rabbit sciatic nerve preparations, and after intraneural injection with the nerve in situ. Two different injection needles were used, one with a bevel angle of 14" and the other with a 45" bevel angle. Fascicular injury was indicated by a fluorescence microscopy technique, tracing locally applied Evans Blue Albumin. The results show that a 45"-bcvcled needle less frequently produces fascicular damage and should therefore be recommended for use in clinical anesthesia. I t is also concluded that paresthesiae, when necessary, should be elicited gently, and that intraneural injections should be avoided.

for the First and Second Trimester Evaluation of Risk (FASTER) Trial Research Consortium* OBJECTIVE: The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. METHODS: A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n‫)690,3؍‬ or did not (control group, n‫)709,13؍‬ undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P‫,47.؍‬ 95% confidence interval-0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). CONCLUSION: The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis.

Drugs with poor oral bioavailability usually are administered by hypodermic injection, which causes pain, poor patient compliance, the need for trained personnel, and risk of infectious disease transmission. Transdermal (TD) delivery provides an excellent alternative, but the barrier ...

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice.

Needle visualization is important for safe and successful ultrasound-guided peripheral nerve block. However, accurate and consistent visualization of the needle tip can be difficult to achieve. This review article describes many of the challenges affecting needle visualization, summarizes the relevant literature on ultrasound imaging of needles, and offers practical strategies for improving needle tip visibility. Finally, future directions for research and development are suggested. Reg Anesth Pain Med 2008;33:532-544.

During acupuncture treatments, acupuncture needles are manipulated to elicit the characteristic "de qi" reaction widely viewed as essential to acupuncture's therapeutic effect. De qi has a biomechanical component, "needle grasp," which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin (pullout force) in 60 human subjects. We hypothesized that pullout force is greater with both bidirectional needle rotation (BI) and unidirectional rotation (UNI) than no rotation (NO). Acupuncture needles were inserted, manipulated, and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points. We found 167 and 52% increases in mean pullout force with UNI and BI, respectively, compared with NO (repeated-measures ANOVA, P Ͻ 0.001). Pullout force was on average 18% greater at acupuncture points than at control points (P Ͻ 0.001). Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation. acupuncture meridians; connective tissue ALTHOUGH ACUPUNCTURE IS INCREASINGLY USED for the treatment of pain and other conditions (27, 37), the rational basis underlying its use remains unclear (2). Western medical experts have been inherently skeptical of acupuncture's therapeutic value. One reason is that it seems very unlikely that the simple act of inserting fine needles into tissue could elicit any effect at all, let alone wide-ranging and long-lasting therapeutic effects. Hypodermic needles are routinely used in Western medicine, and their insertion into the body is not considered therapeutic. Acupuncture needles are of a finer gauge than even the finest needles used for intradermal injections, and acupuncture rarely results in a single drop of blood being discharged. What is not widely appreciated by nonacupuncturists, however, is that acupuncture typically involves manual needle manipulation after needle insertion (3, 6, 16, 33, 40). Manual needle manipulation consists of rapidly rotating (back-and-forth or one direction

In this work, needle insertion into deformable tissue is formulated as a trajectory planning and control problem. A new concept of needle steering has been developed and a needle manipulation Jacobian defined using numerical needle insertion models that include needle deflection and soft tissue deformation. This concept is used in conjunction with a potential-field-based path planning technique to demonstrate needle tip placement and obstacle avoidance. Results from open loop insertion experiments are provided.

n = 8, 2.0%), followed by umbilical hernias ( n = 6, 1.5%) and umbilical wound infection ( n = 5; 1.2%). The rate of penetrating injuries was 0.2% ( n = 1). Of 20 complications, 15 (75%) were related to the umbilical insertion site. Female sex and closed laparoscopy were associated with umbilical morbidity by univariate analysis. In a multivariate analysis, closed laparoscopy was the only factor associated with these complications (odds ratio = 6.0; p = 0.04). Age, gender, obesity, diabetes mellitus, previous abdominal surgery, and the specific procedure had no influence. In conclusion, gaining access to the peritoneal cavity for laparoscopic surgery may cause severe complications, most of which are related to the umbilical trocar. Although closed laparoscopy can be safely used, open laparoscopy is associated with a lower morbidity rate; therefore its utilization is recommended.

Evidence of effectiveness is increasingly used to determine which health technologies are incorporated into public health provision. Acupuncture is a popular therapy that has been shown to be superior to placebo in the treatment of nausea and dental pain, and promising for migraine and osteoarthritis of the knee. For many other conditions, such as chronic pain, in which acupuncture is often used, the evidence is either insufficient or negative. Misleading results may occur for a number of reasons. False negative results may arise from inadequate treatment schedules and inappropriate control interventions. This consensus document considers these issues with the aim of improving the design of efficacy trials of acupuncture in order that they are more likely to be conclusive and more meaningfully interpreted. Clinical trials of acupuncture must use an optimal form of treatment; this can be defined by examining standard texts, by surveying and consulting experts. There are a great many variables in treatment (such as point selection, form of stimulation) all of which need to be addressed in designing and reporting clinical trials. The control procedure is determined by the precise research question that is being addressed. For efficacy studies, in which the question is whether acupuncture has specific effects (i.e. is superior to placebo), sham forms of acupuncture appear the most appropriate method of controlling for needle penetration. A recent development of blunted, telescopic needles may represent a major advance. Such procedures may produce a therapeutic response so should preferably be recorded as 'sham' procedures rather than true 'placebo' controls. Blinding in clinical trials is an accepted means of reducing bias. Patient blinding in acupuncture studies can be achieved by sham procedures and its success should be measured. While practitioner blinding is difficult, though not impossible, blinding of the observer and the analyst should be considered as the ideal for all studies. A number of recommendations are made which aim to improve the quality of sham-controlled acupuncture studies. C

This study aims to compare the therapeutic effectiveness of continuous catheter drainage versus intermittent needle aspiration in the percutaneous treatment of pyogenic liver abscesses. Over a 5-year period, 64 consecutive patients with pyogenic liver abscess were treated with intravenous antibiotics (ampicillin, cefuroxime, and metronidazole) and randomized into two percutaneous treatment groups: continuous catheter drainage (with an 8F multisidehole pigtail catheter); and intermittent needle aspiration (18G disposable trocar needle). There was no statistically significant difference between the two groups regarding patient demographics, underlying coexisting disease, abscess size, abscess number, number of loculation of abscess, the presenting clinical symptoms such as fever, abdominal pain, and pretreatment liver function test. Although not statistically significant, the duration of intravenous antibiotics treatment before percutaneous treatment was longer with the catheter group, and the change of antibiotics after the sensitivity test was more frequent with the needle group. The needle group was associated with a higher treatment success rate, a shorter duration of hospital stay, and a lower mortality rate, although this did not reach statistical significance. In conclusion, this study suggests that intermittent needle aspiration is probably as effective as continuous catheter drainage for the treatment of pyogenic liver abscess, although further proof with a large-scale study is necessary. Due to the additional advantages of procedure simplicity, patient comfort, and reduced price, needle aspiration deserves to be considered as a first-line drainage approach. (HEPATOLOGY 2004;39:932-938.) From the

The efficacy of epidural anaesthesia depends on the accurate identification of the epidural space (ES). Abnormal anatomical conditions may make the procedure difficult or impossible. The aim of this study was to investigate whether prepuncture ultrasound examination of the spinal anatomy might be beneficial in expected cases of difficult epidural anaesthesia. Methods: We used digital ultrasound equipment with a 5-MHz transducer to assess the anatomy of the ES and the posterior parts of the spinal column. We examined 72 parturients with abnormal anatomical conditions who were scheduled for epidural anaesthesia. The women were randomised into two equal groups. In all patients, the standard loss of resistance technique was used. In the ultrasound group, an ultrasound examination of the appropriate spinal region was conducted prior to epidural puncture. ES depth seen on the ultrasound images was com-

Invasomes Skin morphology Transepidermal water loss (TEWL) Drug penetration a b s t r a c t This study focused on the in vitro evaluation of skin perforation using a new microneedle device (Dermaroller ® ) with different needle lengths (150, 500 and 1500 m). The influence of the microneedle treatment on the morphology of the skin surface (studied by light and scanning electron microscopy), on the transepidermal water loss (TEWL) and on the penetration and permeation of hydrophilic model drugs was investigated using excised human fullthickness skin. Furthermore, invasomes -highly flexible phospholipid vesicles containing terpenes and ethanol as penetration enhancer -were compared with an aqueous solution.

This study evaluates the effect of self-selected distracters (ie, bubbles, I Spy: Super Challenger book, music table, virtual reality glasses, or handheld video games) on pain, fear, and distress in 50 children and adolescents with cancer, ages 5 to 18, with port access or venipuncture. Using an intervention-comparison group design, participants were randomized to the comparison group (n = 28) to receive standard care or intervention group (n = 22) to receive distraction plus standard care. All participants rated their pain and fear, parents rated participant fear, and the nurse rated participant fear and distress at 3 points in time: before, during, and after port access or venipuncture. Results show that self-reported pain and fear were significantly correlated (P = .01) within treatment groups but not significantly different between groups. Intervention participants demonstrated significantly less fear (P < .001) and distress (P = .03) as rated by the nurse and approached significantly less fear (P = .07) as rated by the parent. All intervention parents said the needlestick was better because of the distracter. The authors conclude that distraction has the potential to reduce fear and distress during port access and venipuncture.

Previous work has shown that infusion flow rates can be increased by an order of magnitude by partially retracting microneedles after insertion into the skin. This study sought to determine the mechanism by which retraction increases fluid infusion by piercing human cadaver skin with single microneedles, fixing the skin after retracting microneedles to different distances, and examining skin microstructure by histology. We found that microneedle insertion to 1080 μm from the skin surface resulted primarily in skin indentation and only 100-300 μm penetration into the skin. This caused significant compaction of the skin, which probably pressed out most water and thereby dramatically lowered the flow conductivity of skin beneath the needle tip. Retraction of the microneedle allowed the skin to recoil back toward its original position, which relieved the skin compaction and increased local flow conductivity. Altogether, these results suggest that microneedle insertion to penetrate into the skin followed by microneedle retraction to relieve skin compaction is an effective approach to infuse fluid into the skin in a minimally invasive manner.

The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. Methods. Glass microneedles were inserted to a depth of 720Y1080 2m into human cadaver skin to microinfuse sulforhodamine solution at constant pressure. Flow rate was determined as a function of experimental parameters, such as microneedle insertion and retraction distance, infusion pressure, microneedle tip geometry, presence of hyaluronidase, and time. Results. Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15Y96 2l/h. Partial retraction of microneedles increased flow rate up to 11.6-fold. Infusion flow rate was also increased by greater insertion depth, larger infusion pressure, use of a beveled microneedle tip, and the presence of hyaluronidase such that flow rates ranging from 21 to 1130 2l/h were achieved. These effects can be explained by removing or overcoming the large flow resistance imposed by dense dermal tissue, compressed during microneedle insertion, which blocks flow from the needle tip. Conclusions. By partially retracting microneedles after insertion and other methods to overcome flow resistance of dense dermal tissue, protocols can be designed for hollow microneedles to microinfuse fluid at therapeutically relevant rates.

EDITORS' PREFACE: The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP. Ó

The development of needles, needle-insertion simulators, and needle-wielding robots for use in a clinical environment depends on a thorough understanding of the mechanics of needle-tissue interaction. It stands to reason that the forces arising from this interaction are influenced by numerous factors, such as needle type, insertion speed, and tissue characteristics. However, exactly how these factors influence the force is not clear. For this reason, the influence of various factors on needle insertion-force was investigated by searching literature for experimental data. This resulted in a comprehensive overview of experimental insertion-force data available in the literature, grouped by factor for quick reference. In total, 99 papers presenting such force data were found, with typical peak forces in the order of 1-10 N. The data suggest, for example, that higher velocity tends to decrease puncture force and increase friction. Furthermore, increased needle diameter was found to increase peak forces, and conical needles were found to create higher peak forces than beveled needles. However, many questions remain open for investigation, especially those concerning the influence of tissue characteristics.

Recently French rheumatologists have repopularized fasciotomy using a percutaneous needle technique. This blind approach has been claimed to be plagued by numerous complications. We reviewed the charts of 211 patients treated consecutively on 261 hands and 311 fingers to assess the rate of postoperative complications. The first 100 patients were evaluated with a mean follow up of 3.2 years to assess the rate of recurrences and extension of the disease. In the whole group the mean age was 65 years and delay between onset and treatment was 6 years. Division of the cords were performed only in the palm in 165 cases, in the palm and finger in 111 and purely in the finger in 35. Complications were scarce without infection or tendon injury but one digital nerve was found injured during a second procedure. Postoperative gain was prominent at metacarpophalangeal joint level (79% versus 65% at interphalangeal level). The reoperation rate was 24%. In the group assessed at 3.2 years follow up, the recurrence rate was 58% and disease ''activity'' 69%. Fifty nine hands need further surgery. The ideal indication for this simple and reliable technique is an elderly patient with a bowing cord and predominant MP contracture. Chirurgie de la main 2001; 20: 206-211 r 2001 Editions scientifiques et medicales Elsevier SAS. Copyrights S1297-3202(01)0035-X/FLA.

To test the hypothesis that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes in a minimally invasive manner. METHODS. Solid metal microneedles measuring 500 to 750 m in length were coated with model drugs, protein, and DNA; inserted into nonpreserved human cadaveric sclera; and imaged. Microneedles coated with sodium fluorescein were then inserted into rabbit cornea in vivo. After needle removal, fluorescein concentration in the anterior segment of the rabbit eye was measured for 24 hours. Similar experiments were performed using pilocarpine-coated microneedles, and the rabbit pupil size was monitored afterward. RESULTS. In vitro insertion tests showed that microneedles were mechanically strong enough to penetrate into human cadaveric sclera and that the drug coating rapidly dissolved off the needles within the scleral tissue within 30 seconds after insertion. In vivo delivery from fluorescein-coated microneedles showed that fluorescein concentrations in the anterior chamber were 60 times greater than those achieved by topical application without microneedles. Similarly, microneedle delivery of pilocarpine caused rapid and extensive rabbit pupil constriction. There were no measurable inflammatory responses caused by microneedle insertion. CONCLUSIONS. This study demonstrated for the first time that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes. This minimally invasive approach may avoid the complications associated with intraocular injection and systemic administration. (Invest Ophthalmol Vis Sci.

Boutsioukis C, Lambrianidis T, Kastrinakis E. Irrigant flow within a prepared root canal using various flow rates: a Computational Fluid Dynamics study. International Endodontic Journal, 42, 144-155, 2009. Aim To study using computer simulation the effect of irrigant flow rate on the flow pattern within a prepared root canal, during final irrigation with a syringe and needle. Methodology Geometrical characteristics of a sidevented endodontic needle and clinically realistic flow rate values were obtained from previous and preliminary studies. A Computational Fluid Dynamics (CFD) model was created using FLUENT 6.2 software. Calculations were carried out for five selected flow rates (0.02-0.79 mL sec )1 ) and velocity and turbulence quantities along the domain were evaluated.

Background. The rope-ladder puncture technique, with cannulation along the whole length of the vessel traject, has been very common in haemodialysis patients with autogenous arterio-venous fistula (AVF). Today's dialysis population with AVF may exhibit difficult cannulation, because of a short vein length or a complicated cannulation route. An alternative needling possibility is the buttonhole (BH) technique, which inserts needles at exactly the same location during every dialysis session. The present study was conducted to investigate the effect of both cannulation techniques on the incidence of vascular access (VA) complications. Methods. A total of 75 prevalent haemodialysis patients with autogenous AVF using the BH technique were compared with 70 patients using the rope-ladder technique. The following parameters were registered: haematoma occurrence, redness, swelling, aneurysm formation, the use of sharp or dull needles, miscannulations, and interventions. Needling pain and fear of puncture were assessed using a verbal rating scale (VRS). The duration of the follow-up was 9 months. Results. Patients in the BH group had more unsuccessful cannulations, compared with the rope-ladder method (P < 0.0001), but the frequency of haematoma (P < 0.0001) and aneurysm formation (P < 0.0001) was less. In addition, intervention such as angioplasty (P < 0.0001) was higher in patients using the rope-ladder technique. A negative outcome of the BH technique was the higher incidence of access infections compared to the rope-ladder method.

A survey was conducted with the participation of eight consultant general surgeons, two consultant urologists, four consultant orthopaedic surgeons and four surgical residents to find the incidence of accidental injuries to surgeons and their assistants during operations. Of the total of 2016 operations over a one year period there were 112 reported accidental injuries. These included 107 needle stick injuries, 4 knife cuts and 1 diathermy burn. We found that accidental injuries to surgeons during operations were inevitable.

Objectives To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis. Methods Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40-85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection. Results Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with T max 3 times shorter and apparent T 1/2 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40 µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection. Conclusions These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.