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Sample records for nnts khfti ehlektronnyj

  1. A computational study on the application of AlN nanotubes in Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Anaraki-Ardakani, Hossein

    2017-03-01

    We investigated the potential application of the AlN nanotubes (AlNNTs) in Li-ion batteries by means of the density functional theory calculations. To this aim, the interaction of Li atom and Li+ cation with (3 , 3), (4 , 4), (5 , 5), (6 , 6), and (7 , 7) armchair AlNNTs was investigated. By decreasing the curvature of these nanotubes, the HOMO and LUMO levels are shifted to lower and higher energies, thereby enlarging the energy gap. It was found that AlNNTs can produce larger cell voltage in comparison to the carbon nanotubes and may be promising candidate for application in the anode electrode of Li-ion batteries. The calculated cell voltage is in the range of 1.66 to 1.84 V which is significantly increased by increasing the diameter of AlNNTs. The adsorptions of Li and Li+ on the exterior surface of AlNNTs are more favorable than those on its exterior surface. We showed that the interaction of atomic Li with the surface of the AlNNT plays the main rule in determining the cell voltage because of its large dependency on the tube diameter. While the interaction of Li+ is nearly independent of the tube diameter because of the electrostatic nature of the interaction.

  2. The Teaching of Pragmatics by Native and Nonnative Language Teachers: What They Know and What They Report Doing

    ERIC Educational Resources Information Center

    Cohen, Andrew D.

    2016-01-01

    The paper focuses on how nonnative teachers of a target language (NNTs) deal with pragmatics in their classes. It starts with a discussion of what pragmatics entails. Next, issues relating to the teaching of pragmatics are identified, such as the language background of the teacher, comparisons between second- (L2) and foreign-language (FL)…

  3. Fitting a circular distribution based on nonnegative trigonometric sums for wind direction in Malaysia

    NASA Astrophysics Data System (ADS)

    Masseran, Nurulkamal; Razali, Ahmad Mahir; Ibrahim, Kamarulzaman; Zaharim, Azami; Sopian, Kamaruzzaman

    2015-02-01

    Wind direction has a substantial effect on the environment and human lives. As examples, the wind direction influences the dispersion of particulate matter in the air and affects the construction of engineering structures, such as towers, bridges, and tall buildings. Therefore, a statistical analysis of the wind direction provides important information about the wind regime at a particular location. In addition, knowledge of the wind direction and wind speed can be used to derive information about the energy potential. This study investigated the characteristics of the wind regime of Mersing, Malaysia. A circular distribution based on Nonnegative Trigonometric Sums (NNTS) was fitted to a histogram of the average hourly wind direction data. The Newton-like manifold algorithm was used to estimate the parameter of each component of the NNTS model. Next, the suitability of each NNTS model was judged based on a graphical representation and Akaike's Information Criteria. The study found that the NNTS model with six or more components was able to fit the wind directional data for the Mersing station.

  4. The Evolution of NATO with Four Plausible Threat Scenarios

    DTIC Science & Technology

    1987-08-01

    with war, done with brutal and bloody methods of settling our disputes .... 29. Briand’s view was reciprocated by Gustav Stresemann, Germany’s...NE.THERLANDS L"EBRERTT EAST GERMANY ""I W HESSIAN HILL S Mag £Cologne )! RUHTHIU N MTA. BRnCE Stutt gart • RTA (5) MTS.NNTS DANUB R( Bon ., FuldaIN OHMANMS

  5. Reliable evidence for efficacy of single dose oral analgesics.

    PubMed

    Spivakovsky, Silvia; Spivakovsky, Yael

    2016-06-01

    Data sourcesThe Cochrane library was searched for Cochrane systematic reviews.Study selectionCochrane reviews on single pain medications for the treatment of acute pain were included. Non-Cochrane reviews were included for tramadol.Data extraction and synthesisTwo reviewers independently searched, selected reviews for inclusion, assessed quality and performed data extraction. A protocol in case of disagreement was in place. Data were collected on number of included studies and participants, drug, dose and formulation and pain model. The authors concentrated on the amount of information and the potential for publication bias.Pain relief was calculated using at least 50% maximum pain relief, as a percentage, and as NNTs. Duration of analgesia was measured as mean or median and time to remedication was calculated as percentage of patients.ResultsThirty-nine reviews including 41 interventions were analysed and NNTs for at least 50% maximum pain relief were summarised in a graphic. NNTs range from almost one all the way to five. Only one intervention, codeine 60, had an NNT ≥10. Results judged to be reliable were listed in detail. Mean or median time to remedication was also presented in a graphic.The authors conclude that there is a great amount of quality information on single dose analgesics, and highlighted the potential benefit of fast acting formulations and fixed formulations to achieve good long-lasting analgesia.ConclusionsThere is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

  6. High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study

    PubMed Central

    Hadaegh, Farzad; Bozorgmanesh, Mohammad Reza; Ghasemi, Asghar; Harati, Hadi; Saadat, Navid; Azizi, Fereidoun

    2008-01-01

    Background To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years. Methods The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes. Results The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4). Conclusion In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient. PMID:18501007

  7. How patient outcomes are reported in drug advertisements.

    PubMed Central

    Lexchin, J.

    1999-01-01

    OBJECTIVE: To examine how changes in outcomes are reported in drug advertisements in medical journals. QUALITY OF EVIDENCE: Advertisements from a convenience sample of 38 issues of Canadian Family Physician, Canadian Journal of Anaesthesia, Canadian Journal of Psychiatry, Canadian Medical Association Journal, and the New England Journal of Medicine. MAIN MESSAGE: Method of reporting changes in clinical outcomes (relative risk reduction [RRR], absolute risk reduction [ARR], number needed to treat [NNT]), name of product, and company marketing product were sought. In the 22 advertisements included in the analysis, 11 reported results as RRRs; two reported results as RRRs, but readers could calculate ARRs or NNTs from figures given in the advertisement; and nine gave no measure of results, but readers could calculate RRRs, ARRs, or NNTs from figures given. CONCLUSIONS: Most companies report changes in outcomes as RRRs, and this bias could influence the way physicians prescribe. Changes to the rules governing journal advertising and increased emphasis on critical appraisal skills would help mitigate this bias. PMID:10349065

  8. Testing for seasonality using circular distributions based on non-negative trigonometric sums as alternative hypotheses.

    PubMed

    Fernández-Durán, J J; Gregorio-Domínguez, M M

    2014-06-01

    In medical and epidemiological studies, the importance of detecting seasonal patterns in the occurrence of diseases makes testing for seasonality highly relevant. There are different parametric and non-parametric tests for seasonality. One of the most widely used parametric tests in the medical literature is the Edwards test. The Edwards test considers a parametric alternative that is a sinusoidal curve with one peak and one trough. The Cave and Freedman test is an extension of the Edwards test that is also frequently applied and considers a sinusoidal curve with two peaks and two troughs as the alternative hypothesis. The Kuiper, Hewitt and David and Newell are common non-parametric tests. Fernández-Durán (2004) developed a family of univariate circular distributions based on non-negative trigonometric (Fourier) sums (series) (NNTS) that can account for an arbitrary number of peaks and troughs. In this article, this family of distributions is used to construct a likelihood ratio test for seasonality considering parametric alternative hypotheses that are NNTS distributions.

  9. The microcantilever array: a low-power, compact, and sensitive unattended sensor technology

    NASA Astrophysics Data System (ADS)

    Rogers, B.; Whitten, R.; Adams, J. D.

    2005-10-01

    In an unattended, implanted or mobile ground sensor scenario, the microcantilever platform is well suited: sensor power consumption has been demonstrated at the nanowatt level and, as a microelectromechanical system, the platform is inherently compact. In addition, the remarkable sensitivity, low cost, scalability, durability and versatility of microcantilever sensors make this technology among the most promising solutions for unattended ground sensing of chemical and biological agents, as well as explosives. Nevada Nanotech Systems, Inc (NNTS) is developing a microcantilever- based detection system that will measure trace concentrations of explosives, toxic chemicals, and biological agents in air. A baseline sensor unit that includes the sensor array, electronics, power supply and air handling has been designed and preliminary demonstrations of the microcantilever platform have been conducted. The envisioned device would measure about two cubic inches, run on a small watch battery and cost a few hundred dollars. Finally, the NNTS microcantilever sensor has potential as a multifunctional transducer for enhancing detection and discrimination. Recent test results using this platform will be discussed.

  10. Stability, electronic structures and transport properties of armchair (10, 10) BN/C nanotubes

    SciTech Connect

    Xiao, H.P.; He, Chaoyu; Zhang, C.X.; Sun, L.Z.; Zhou, Pan; Zhong, Jianxin

    2013-04-15

    Using the first-principle calculations, the stability and electronic properties of two novel types of four-segment armchair (10, 10) BN/C hybrid nanotubes ((BN){sub 5}C{sub 5}(BN){sub 5}C{sub 5}NT and (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT) as well as two-segment armchair (10, 10) BN/C hybrid nanotubes ((BN{sub 20−n}C{sub n}NTs) are systematically investigated. When n increases from 1 to 4, the band gap of (BN){sub 20−n}C{sub n}NTs gradually decreases to a narrow one. When 4≤n≤17, the electronic structure of carbon segment in (BN){sub 20−n}C{sub n}NTs behaves as zigzag graphene nanoribbons whose band gap is modulated by an inherent electric field of the BN segment. ZGNR-like segments in (BN){sub 5}C{sub 5}(BN){sub 5}C{sub 5}NT and (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT behave as narrow gap semiconductor and metal, respectively, due to their different chemical environment. Moreover, the (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT can separate electron and hole carriers, indicating its potential application in solar cell materials. Obvious transport enhancement around the Fermi level is found in the four-segment nanotubes, especially a 6G{sub 0} transmission peak in the metallic (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT. - Graphical abstract: Structural diagram of four-segment (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT and its typical two-probe system. The band structures and transport spectra of (BN){sub 5}C{sub 5}(NB){sub 5}C{sub 5}NT are shown in upper and lower panels. Highlights: ► Transport properties of two types of four-segment BNC hybrid nanotubes are studied. ► Transport enhancements are realized in the four-segment BNC hybrid nanotubes. ► Electron and hole separation is found in four-segment BNC hybrid nanotubes.

  11. Sumatriptan (oral route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Objectives To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during

  12. Electrical breakdown of carbon nanotube devices and the predictability of breakdown position

    NASA Astrophysics Data System (ADS)

    Goswami, Gopal Krishna; Nanda, Karuna Kar

    2012-06-01

    We have investigated electrical transport properties of long (>10 μm) multiwalled carbon nanotubes (NTs) by dividing individuals into several segments of identical length. Each segment has different resistance because of the random distribution of defect density in an NT and is corroborated by Raman studies. Higher is the resistance, lower is the current required to break the segments indicating that breakdown occurs at the highly resistive segment/site and not necessarily at the middle. This is consistent with the one-dimensional thermal transport model. We have demonstrated the healing of defects by annealing at moderate temperatures or by current annealing. To strengthen our mechanism, we have carried out electrical breakdown of nitrogen doped NTs (NNTs) with diameter variation from one end to the other. It reveals that the electrical breakdown occurs selectively at the narrower diameter region. Overall, we believe that our results will help to predict the breakdown position of both semiconducting and metallic NTs.

  13. A systematic review of the preventive effect of oral hygiene on pneumonia and respiratory tract infection in elderly people in hospitals and nursing homes: effect estimates and methodological quality of randomized controlled trials.

    PubMed

    Sjögren, Petteri; Nilsson, Erika; Forsell, Marianne; Johansson, Olle; Hoogstraate, Janet

    2008-11-01

    The objective of this study was to investigate the preventive effect of oral hygiene on pneumonia and respiratory tract infection, focusing on elderly people in hospitals and nursing homes, by systematically reviewing effect estimates and methodological quality of randomized controlled trials (RCTs) and to provide an overview of additional clinical studies in this area. Literature searches were conducted in the Medline database, the Cochrane library databases, and by hand-searching reference lists. Included publications were analyzed for intervention (or topic) studied, main conclusions, strength of evidence, and study design. RCTs were further analyzed for effect magnitudes and methodological details. Absolute risk reductions (ARRs) and numbers needed to treat (NNTs) were calculated. Fifteen publications fulfilled the inclusion criteria. There was a wide variation in the design and quality of the studies included. The RCTs revealed positive preventive effects of oral hygiene on pneumonia and respiratory tract infection in hospitalized elderly people and elderly nursing home residents, with ARRs from 6.6% to 11.7% and NNTs from 8.6 to 15.3 individuals. The non-RCT studies contributed to inconclusive evidence on the association and correlation between oral hygiene and pneumonia or respiratory tract infection in elderly people. Mechanical oral hygiene has a preventive effect on mortality from pneumonia, and non-fatal pneumonia in hospitalized elderly people and elderly nursing home residents. Approximately one in 10 cases of death from pneumonia in elderly nursing home residents may be prevented by improving oral hygiene. Future research in this area should be focused on high-quality RCTs with appropriate sample size calculations.

  14. Number needed to treat: solid science or a path to pernicious rationing?

    PubMed

    Black, H R; Crocitto, M T

    1998-08-01

    Basing clinical practice decisions on currently available evidence from clinical trials may result in suboptimal care in the real-world practice of medicine. The problem stems from both the quality of data and the means by which the data have been interpreted. In an attempt to remedy the situation, a term based on an assessment of all risk factors and comorbidity has been suggested and made more easily translatable to clinical decision making. This term, the reciprocal of absolute risk reduction, is the number needed to treat (NNT), an idea that has gained wide acceptance. There are, however, risks that the simplicity of the NNT will be misused to guide reimbursement decisions and potentially prevent patients from receiving optimal care. This seemingly objective measure may be seriously flawed if the data on which this measure is based do not necessarily reflect the results that real world doctors achieve in practice. These problems could lead to the misguided allocation of health care resources. It is therefore incumbent upon us to closely evaluate the data on which NNTs are based and, if necessary, to arrive at more accurate NNTs. In our view, such data should be gleaned from effectiveness trials done by real world doctors in real world settings with real world volunteers. Large simple trials, as have already been performed in a number of therapeutic areas, especially for acute management of myocardial infarction and in acquired immune deficiency syndrome, offer the best likelihood of yielding this crucial information. We need to be sure that future trials of chronic conditions such as hypertension are done with this trial paradigm, so that those who pay for care have the accurate knowledge needed to spend their money wisely.

  15. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    SciTech Connect

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel . E-mail: s-hellman@uchicago.edu

    2005-03-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term ({<=}6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

  16. Ibuprofen with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Rabbie, Roy; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers do not seek professional help, relying instead on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce symptoms commonly associated with migraine headaches. Objectives To determine efficacy and tolerability of ibuprofen, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 22 April 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using self-administered ibuprofen to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and number needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Nine studies (4373 participants, 5223 attacks) compared ibuprofen with placebo or other active comparators; none combined ibuprofen with a self-administered antiemetic. All studies treated attacks with single doses of medication. For ibuprofen 400 mg versus placebo, NNTs for 2-hour pain-free (26% versus 12% with placebo), 2-hour headache relief (57% versus 25%) and 24-hour sustained headache relief (45% versus 19%) were 7.2, 3.2 and 4.0, respectively. For ibuprofen 200 mg versus placebo, NNTs for 2-hour pain-free (20% versus 10%) and 2-hour headache relief (52% versus 37%) were 9.7 and 6.3, respectively. The higher dose was significantly better for 2-hour headache relief than the lower dose. Soluble formulations of ibuprofen 400 mg were better than standard tablets for 1-hour, but not 2-hour headache relief

  17. Sumatriptan (rectal route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Rectal administration may be preferable to oral for individuals experiencing nausea and/or vomiting. Objectives To determine the efficacy and tolerability of rectal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using rectally administered sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Three studies (866 participants) compared rectally administered sumatriptan with placebo or an active comparator. Most of the data were for the 12.5 mg and 25 mg doses. For the majority of efficacy outcomes, sumatriptan surpassed placebo. For sumatriptan 12.5 mg versus placebo the NNTs were 5.2 and 3.2 for headache relief at one and two hours, respectively. Results for the 25 mg dose were similar to the 12.5 mg dose, and there were no significant differences between the two doses for any of the outcomes analysed. The NNTs for sumatriptan 25 mg versus placebo were 4.2, 3.2, and 2.4 for pain-free at two hours, headache relief at one hour, and headache relief at two hours, respectively. Relief of functional

  18. Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations

    PubMed Central

    Finnerup, Nanna B; Attal, Nadine; Haroutounian, Simon; McNicol, Ewan; Baron, Ralf; Dworkin, Robert H; Gilron, Ian; Haanpaa, Maija; Hansson, Per; Jensen, Troels S; Kamerman, Peter R; Lund, Karen; Moore, Andrew; Raja, Srinivasa N; Rice, Andrew SC; Rowbotham, Michael; Sena, Emily; Siddall, Philip; Smith, Blair H; Wallace, Mark

    2015-01-01

    Summary Background Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment. Methods The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Findings In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R2=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin

  19. Sumatriptan (intranasal route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Intranasal administration may be preferable to oral for individuals experiencing nausea and/or vomiting, although it is primarily absorbed in the gut, not the nasal mucosa. Objectives To determine the efficacy and tolerability of intranasal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using intranasal sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Twelve studies (4755 participants) compared intranasal sumatriptan with placebo or an active comparator. Most of the data were for the 10 mg and 20 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 10 mg versus placebo the NNTs were 7.3, 7.4, and 5.5 for pain-free at two hours, and headache relief at one and two hours, respectively. For sumatriptan 20 mg versus placebo the NNTs were 4.7, 4.9, and 3.5, respectively, for the same outcomes. The 20 mg dose was significantly better than the 10 mg dose for each of these three primary efficacy outcomes. Relief of headache-associated symptoms, including nausea, photophobia, and

  20. Microcantilever technology for law enforcement and anti-terrorism applications: chemical, biological, and explosive material detection

    NASA Astrophysics Data System (ADS)

    Adams, J. D.; Rogers, B.; Whitten, R.

    2005-05-01

    The remarkable sensitivity, compactness, low cost, low power-consumption, scalability, and versatility of microcantilever sensors make this technology among the most promising solutions for detection of chemical and biological agents, as well as explosives. The University of Nevada, Reno, and Nevada Nanotech Systems, Inc (NNTS) are currently developing a microcantilever-based detection system that will measure trace concentrations of explosives, toxic chemicals, and biological agents in air. A baseline sensor unit design that includes the sensor array, electronics, power supply and air handling has been created and preliminary demonstrations of the microcantilever platform have been conducted. The envisioned device would measure about two cubic inches, run on a small watch battery and cost a few hundred dollars. The device could be operated by untrained law enforcement personnel. Microcantilever-based devices could be used to "sniff out" illegal and/or hazardous chemical and biological agents in high traffic public areas, or be packaged as a compact, low-power system used to monitor cargo in shipping containers. Among the best detectors for such applications at present is the dog, an animal which is expensive, requires significant training and can only be made to work for limited time periods. The public is already accustomed to explosives and metal detection systems in airports and other public venues, making the integration of the proposed device into such security protocols straightforward.

  1. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis.

    PubMed

    Cusack, Karen; Jonas, Daniel E; Forneris, Catherine A; Wines, Candi; Sonis, Jeffrey; Middleton, Jennifer Cook; Feltner, Cynthia; Brownley, Kimberly A; Olmsted, Kristine Rae; Greenblatt, Amy; Weil, Amy; Gaynes, Bradley N

    2016-02-01

    Numerous guidelines have been developed over the past decade regarding treatments for Posttraumatic stress disorder (PTSD). However, given differences in guideline recommendations, some uncertainty exists regarding the selection of effective PTSD therapies. The current manuscript assessed the efficacy, comparative effectiveness, and adverse effects of psychological treatments for adults with PTSD. We searched MEDLINE, Cochrane Library, PILOTS, Embase, CINAHL, PsycINFO, and the Web of Science. Two reviewers independently selected trials. Two reviewers assessed risk of bias and graded strength of evidence (SOE). We included 64 trials; patients generally had severe PTSD. Evidence supports efficacy of exposure therapy (high SOE) including the manualized version Prolonged Exposure (PE); cognitive therapy (CT), cognitive processing therapy (CPT), cognitive behavioral therapy (CBT)-mixed therapies (moderate SOE); eye movement desensitization and reprocessing (EMDR) and narrative exposure therapy (low-moderate SOE). Effect sizes for reducing PTSD symptoms were large (e.g., Cohen's d ~-1.0 or more compared with controls). Numbers needed to treat (NNTs) were <4 to achieve loss of PTSD diagnosis for exposure therapy, CPT, CT, CBT-mixed, and EMDR. Several psychological treatments are effective for adults with PTSD. Head-to-head evidence was insufficient to determine these treatments' comparative effectiveness, and data regarding adverse events was absent from most studies.

  2. Pharmacotherapy for Pediatric Generalized Anxiety Disorder: A Systematic Evaluation of Efficacy, Safety and Tolerability

    PubMed Central

    Dobson, Eric T.; Strawn, Jeffrey R.

    2016-01-01

    Background Randomized controlled trials consistently support the efficacy of antidepressants in treating youth with generalized anxiety disorder (GAD), although integrated examinations of efficacy, safety, and tolerability of psychotropic medications in GAD specifically are rare. With this in mind, we sought to describe the efficacy, safety and tolerability of psychopharmacologic interventions in youth with GAD. Methods Randomized, double-blind, placebo-controlled, prospective trials of psychopharmacologic interventions in youth with GAD were identified through a PubMed/Medline (1966–2015) search. Both authors manually reviewed trials and, to evaluate comparative efficacy and tolerability across medications, numbers needed to treat (NNT) (based on Pediatric Anxiety Rating Scale (PARS) remission criteria (PARS ≤8 [1]), and number needed to harm (NNH) for selected treatment-emergent adverse events (TEAEs) were calculated. Finally, treatment-emergent suicidality and taper-emergent/post-study adverse events are reported descriptively. Results Five trials that involved 1,186 patients and evaluated four medications were reviewed and efficacy data were extracted with regard to dimensional measures of anxiety. SSRI/SNRIs demonstrated efficacy in the reduction of anxiety symptoms with NNTs ranging from 2.8 to 9.3. TEAEs varied considerably between studies but tended to be mild and generally did not lead to discontinuation. Conclusions Data from five trials of SSRI/SNRI in youth with GAD, many of whom had co-occurring separation and social anxiety disorders, suggest superiority to placebo and favorable tolerability profiles. PMID:26660158

  3. A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine.

    PubMed

    Moore, R A; Derry, C J; Derry, S; Straube, S; McQuay, H J

    2012-04-01

    Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. We tested measured effects of combination analgesics against the sum of the absolute benefits in acute pain and migraine using meta-analysis where individual components and combinations were tested against placebo in the same trials, and verified the result with meta-analyses where individual components and combinations were tested against placebo in different trials. Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects.

  4. Population Attributable Risk Fractions of Maternal Overweight and Obesity for Adverse Perinatal Outcomes.

    PubMed

    MacInnis, Natasha; Woolcott, Christy G; McDonald, Sarah; Kuhle, Stefan

    2016-03-10

    The objective of the current study was to determine the proportion of adverse perinatal outcomes that could be potentially prevented if maternal obesity were to be reduced or eliminated (population attributable risk fractions, PARF); and the number needed to treat (NNT) of overweight or obese women to prevent one case of adverse perinatal outcome. Data from the Atlee Perinatal Database on 66,689 singleton infants born in Nova Scotia, Canada, between 2004 and 2014, and their mothers were used. Multivariable-adjusted PARFs and NNTs of maternal pre-pregnancy weight status were determined for various perinatal outcomes under three scenarios: If all overweight and obese women were to i) become normal weight before pregnancy; ii) shift down one weight class; or iii) lose 10% of their body weight, significant relative reductions would be seen for gestational diabetes mellitus (GDM, 57/33/15%), hypertensive disorders of pregnancy (HDP, 26/16/6%), caesarean section (CS, 18/10/3%), and large for gestational age births (LGA, 24/14/3%). The NNT were lowest for the outcomes GDM, induction of labour, CS, and LGA, where they ranged from 13 to 73. The study suggests that a substantial proportion of adverse perinatal outcomes may be preventable through reductions in maternal pre-pregnancy weight.

  5. Absolute risks rather than incidence rates should be used to estimate the number needed to treat from time-to-event data.

    PubMed

    Bender, Ralf; Kromp, Mandy; Kiefer, Corinna; Sturtz, Sibylle

    2013-09-01

    When estimating the number needed to treat (NNT) from randomized controlled trials (RCTs) with time-to-event outcomes, varying follow-up times have to be considered. Two methods have been proposed, namely (1) inverting risk differences estimated by survival time methods (RD approach) and (2) inverting incidence differences (ID approach). A simulation study was conducted to compare the RD and the ID approaches regarding bias and coverage probability (CP) considering various distributions, baseline risks, effect sizes, and sample sizes. Additionally, the two approaches were compared by using two real data examples. The RD approach showed good estimation and coverage properties with only a few exceptions in the case of small sample sizes and small effect sizes. The ID approach showed considerable bias and low CPs in most of the considered data situations. Absolute risks estimated by means of survival time methods rather than incidence rates should be used to estimate NNTs in RCTs with time-to-event outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The microcantilever array: a low power, compact, and sensitive unattended ground sensor

    NASA Astrophysics Data System (ADS)

    Adams, J. D.; Rogers, B.; Whitten, R.

    2005-05-01

    In an unattended implanted or mobile ground sensor scenario, the microcantilever platform is well suited: sensor power consumption has been demonstrated at the nanowatt level and, as a microelectromechanical system, the platform is inherently compact. In addition, the remarkable sensitivity, low cost, scalability, and versatility of microcantilever sensors make this technology among the most promising solutions for unattended ground sensing of chemical and biological agents, as well as explosives. The University of Nevada, Reno, and Nevada Nanotech Systems, Inc (NNTS) are currently developing a microcantilever-based detection system that will measure trace concentrations of explosives, toxic chemicals, and biological agents in air. A baseline sensor unit that includes the sensor array, electronics, power supply and air handling has been designed and preliminary demonstrations of the microcantilever platform have been conducted. The envisioned device would measure about two cubic inches, run on a small watch battery and cost a few hundred dollars. This first design is tailored to shipping container monitoring, but is a broadly applicable device for passive or active monitoring scenarios.

  7. Assessing neurosurgical non-technical skills: an exploratory study of a new behavioural marker system.

    PubMed

    Michinov, Estelle; Jamet, Eric; Dodeler, Virginie; Haegelen, Claire; Jannin, Pierre

    2014-10-01

    The management of non-technical skills is a major factor affecting teamwork quality and patient safety. This article presents a behavioural marker system for assessing neurosurgical non-technical skills (BMS-NNTS). We tested the BMS during deep brain stimulation surgery. We developed the BMS in three stages. First, we drew up a provisional assessment tool based on the literature and observation tools developed for other surgical specialties. We then analysed videos made in an operating room (OR) during deep brain stimulation operations in order to ensure there were no significant omissions from the skills list. Finally, we used five videos of operations to identify the behavioural markers of non-technical skills in verbal communications. Analyses of more than six hours of observations revealed 3515 behaviours from which we determined the neurosurgeon's non-technical skills behaviour pattern. The neurosurgeon frequently engaged in explicit coordination, situation awareness and leadership behaviours. In addition, the neurosurgeon's behaviours differed according to the stage of the operation and the OR staff members with whom she was communicating. Our behavioural marker system provides a structured approach to assessing non-technical skills in the field of neurosurgery. It can also be transferred to other surgical specialties and used in surgeon training curricula. © 2014 John Wiley & Sons, Ltd.

  8. Providing additional information about the benefits of statins in a leaflet for patients with coronary heart disease: a qualitative study of the impact on attitudes and beliefs

    PubMed Central

    Dickinson, Rebecca; Raynor, David K; MacDonald, Jan

    2016-01-01

    Objective To explore the impact of providing additional information about the potential benefits of simvastatin in a patient leaflet on attitudes and beliefs. Design Interview-based study using a generic qualitative approach and framework analysis. Participants 21 participants receiving a prescription for simvastatin were recruited from a general practitioner practice (from a total of 120). 8 participants were women; the age range was 55–92. Intervention Participants were provided with leaflets showing one of 3 types of additional benefit information: (1) textual statement, (2) number needed to treat (NNT) or (3) natural frequency. Semistructured interviews explored patient's attitudes and beliefs. Results A descriptive narrative of preferences for format suggested patients prefer textual as opposed to numerical benefit information. Significant barriers to the acceptance of numerical benefit information included difficulty in understanding the numbers. Patients overestimated the benefits of statins and expressed surprise at the numerical information. Conclusions Textual information was preferred but numerical information, in particular in the form of a natural frequency, may help patients make judgements about their medicines. NNTs were found to be very difficult to understand. This raises the prospect that some patients might reject medicines because of disappointment with the perceived low benefits of their medicines. The self-reported impact on behaviour appeared minimal with reports of intentions to ‘do what the doctor tells me’. Further research is needed to explore the impact of such statements on people who are yet to be prescribed a statin. PMID:27913558

  9. Electric field effect on (6,0) zigzag single-walled aluminum nitride nanotube.

    PubMed

    Baei, Mohammad T; Peyghan, Ali Ahmadi; Moghimi, Masoumeh

    2012-09-01

    Structural, electronic, and electrical responses of the H-capped (6,0) zigzag single-walled aluminum nitride nanotube was studied under the parallel and transverse electric fields with strengths 0-140 × 10(-4) a.u. by using density functional calculations. Geometry optimizations were carried out at the B3LYP/6-31G* level of theory using a locally modified version of the GAMESS electronic structure program. The dipole moments, atomic charge variations, and total energy of the (6,0) zigzag AlNNT show increases with increase in the applied external electric field strengths. The length, tip diameters, electronic spatial extent, and molecular volume of the nanotube do not significantly change with increasing electric field strength. The energy gap of the nanotube decreases with increases of the electric field strength and its reactivity is increased. Increase of the ionization potential, electron affinity, chemical potential, electrophilicity, and HOMO and LUMO in the nanotube with increase of the applied parallel electric field strengths shows that the parallel field has a much stronger interaction with the nanotube with respect to the transverse electric field strengths. Analysis of the parameters indicates that the properties of AlNNTs can be controlled by the proper external electric field.

  10. First-principles study of nanotubes within the tetragonal, hexagonal and dodecagonal cycle structures

    NASA Astrophysics Data System (ADS)

    BabaeiPour, M.; Safari, E. Keshavarz; Shokri, A. A.

    2017-02-01

    A systematic study has been done on the structural and electronic properties of carbon, boron nitride and aluminum nitride nanotubes with structure consisting of periodically distributed tetragonal (T ≡A2X2), hexagonal (H ≡A3X3) and dodecagonal (D ≡A6X6) (AX=C2, BN, AlN) cycles. The method has been performed using first-principles calculations based on density functional theory (DFT). The optimized lattice parameters, density of state (DOS) curves and band structure of THD-NTs are obtained for (3, 0) and (0, 2) types. Our calculation results indicate that carbon nanotubes of these types (THD-CNTs) behave as a metallic, but the boron nitride nanotubes (THD-BNNTs) (with a band gap of around 4 eV) as well as aluminum nitride nanotubes (THD-AlNNTs) (with a band gap of around 2.6 eV) behave as an semiconductor. The inequality in number of atoms in different directions is affected on structures and diameters of nanotubes and their walls curvature.

  11. NMR and NQR study of Si-doped (6,0) zigzag single-walled aluminum nitride nanotube as n or P-semiconductors.

    PubMed

    Baei, Mohammad T; Peyghan, Ali Ahmadi; Tavakoli, Khadijeh; Babaheydari, Ali Kazemi; Moghimi, Masoumeh

    2012-09-01

    Density functional theory (DFT) calculations were performed to investigate the electronic structure properties of pristine and Si-doped aluminum nitride nanotubes as n or P-semiconductors at the B3LYP/6-31G* level of theory in order to evaluate the influence of Si-doped in the (6,0) zigzag AlNNTs. We extended the DFT calculation to predict the electronic structure properties of Si-doped aluminum nitride nanotubes, which are very important for production of solid-state devices and other applications. To this aim, pristine and Si-doped AlNNT structures in two models (Si(N) and Si(Al)) were optimized, and then the electronic properties, the isotropic (CS(I)) and anisotropic (CS(A)) chemical shielding parameters for the sites of various (27)Al and (14)N atoms, NQR parameters for the sites of various of (27)Al and (14)N atoms, and quantum molecular descriptors were calculated in the optimized structures. The optimized structures, the electronic properties, NMR and NQR parameters, and quantum molecular descriptors for the Si(N) and Si(Al) models show that the Si(N) model is a more reactive material than the pristine or Si(Al) model.

  12. WITHDRAWN. Anticonvulsant drugs for acute and chronic pain.

    PubMed

    Wiffen, Philip J; Collins, Sally; McQuay, Henry J; Carroll, Dawn; Jadad, Alejandro; Moore, R Andrew

    2010-01-20

    Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. Readers are referred to reviews of carbamazepine and gabapentin in T he Cochrane Library which replace the information on those drugs in this review. Other drugs remain unchanged at present in this review To evaluate the analgesic effectiveness and adverse effects of anticonvulsant drugs for pain management in clinical practice . Migraine and headache studies are excluded in this revision. Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by MEDLINE (1966-1999), EMBASE (1994-1999), SIGLE (1980 to 1999) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (The Cochrane Library Issue 3, 1999). In addition, 41 medical journals were hand searched. Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: September 1999. Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with subjective pain assessment as either the primary or a secondary outcome. Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. Twenty-three trials of six anticonvulsants were considered eligible (1074 patients).The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate.Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT (95% confidence interval (CI)) for effectiveness of 2.5 (CI 2.0 to 3.4). A single placebo-controlled trial of gabapentin in post-herpetic neuralgia had an NNT of 3.2 (CI 2.4 to 5.0). For diabetic neuropathy NNTs for effectiveness

  13. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. Objectives To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6). Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan

  14. Nonsteroidal Anti-Inflammatory Drugs, Gastroprotection, and Benefit–Risk

    PubMed Central

    Moore, Robert Andrew; Derry, Sheena; Simon, Lee S; Emery, Paul

    2014-01-01

    Background Gastroprotective agents (GPA) substantially reduce morbidity and mortality with long-term nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin. Objective To evaluate efficacy of NSAIDs, protection against NSAID-induced gastrointestinal harm, and balance of benefit and risk. Methods Free text searches of PubMed (December 2012) supplemented with “related citation” and “cited by” facilities on PubMed and Google Scholar for patient requirements, NSAID effectiveness, pain relief benefits, gastroprotective strategies, adherence to gastroprotection prescribing, and serious harm with NSAIDs and GPA. Results Patients want 50% reduction in pain intensity and improved fatigue, distress, and quality of life. Meta-analyses of NSAID trials in musculoskeletal conditions had bimodal responses with good pain relief or little. Number needed to treat (NNTs) for good pain relief were 3 to 9. Proton pump inhibitors (PPI) and high-dose histamine-2 receptor antagonists (H2RA) provided similar gastroprotection, with no conclusive evidence of greater PPI efficacy compared with high-dose H2RA. Prescriber adherence to guidance on use of GPA with NSAIDS was 49% in studies published since 2005; patient adherence was less than 100%. PPI use at higher doses over longer periods is associated with increased risk of serious adverse events, including fracture; no such evidence was found for H2RA. Patients with chronic conditions are more willing to accept risk of harm for successful treatment than their physicians. Conclusion Guidance on NSAIDs use should ensure that patients have a good level of pain relief and that gastroprotection is guaranteed for the NSAID delivering good pain relief. Fixed-dose combinations of NSAID plus GPA offer one solution. PMID:23941628

  15. Cost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision.

    PubMed

    Alzahouri, Kazem; Bahrami, Stéphane; Durand-Zaleski, Isabelle; Guillemin, Francis; Roux, Christian

    2013-01-01

    FRAX™ is a fracture prediction algorithm to determine a patient's absolute fracture risk. There is a growing consensus that osteoporosis treatment should be based on individual 10-year fracture probability, as calculated in the FRAX™ algorithm, rather than on T-scores alone. Our objective was to evaluate the cost-effectiveness of five years of branded alendronate therapy in postmenopausal French women with a known FRAX™ score. A Markov cohort state transition model using FRAX™ values and whenever possible population-specific data and probabilities. We estimated the incremental cost-effectiveness ratio (ICER) of alendronate versus no treatment in postmenopausal women with FRAX™ ranging from 10 to 3%. Number of women to treat (NNT) for preventing hip fracture, costs, quality-adjusted life-years, incremental cost-effectiveness ratios. The incremental cost-effectiveness ratios (ICER) compared to no treatment at age 70 ranged from €104,183 to €413,473 per QALY when FRAX™ decreased from 10 to 3%. The NNTs for preventing one hip fracture ranged from 97 to 388 according to age (50-80 years) and FRAX™. Sensitivity analyses showed that the main determinants of cost-effectiveness were adherence to therapy and cost of treatment. Using French costs of branded drug and current estimates of treatment efficacy, alendronate therapy for 70-year-old women with 10-year probability of hip fracture of 10% just meets the accepted cost-effectiveness threshold. Improving treatment adherence and/or decreasing treatment cost lowers the ICER. The model however underestimates the potential benefit by excluding other fractures. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  16. Low-dose vaporized cannabis significantly improves neuropathic pain.

    PubMed

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  17. Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary Assessment Based on Number Needed to Treat.

    PubMed

    Fairman, Kathleen A; Davis, Lindsay E; Kruse, Courtney R; Sclar, David A

    2017-04-01

    Faced with rising healthcare costs, state Medicaid programs need short-term, easily calculated budgetary estimates for new drugs, accounting for medical cost offsets due to clinical advantages. To estimate the budgetary impact of direct-acting oral anticoagulants (DOACs) compared with warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to treat (NNT). Medicaid utilization files, 2009 through second quarter 2015, were used to estimate OAC cost accounting for generic/brand statutory minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were calculated from clinical trial reports to estimate avoided medical events for a hypothetical population of 500,000 enrollees (approximate NVAF prevalence × Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50% increase. Medical service costs were based on published sources. Costs were inflation-adjusted (2015 US$). From 2009-2015, OAC reimbursement per claim increased by 173 and 279% under maximum and minimum rebate scenarios, respectively, while DOAC market share increased from 0 to 21%. Compared with a warfarin-only counterfactual, counts of ischemic strokes, intracranial hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively; counts of gastrointestinal hemorrhages increased by 794. Avoided events and reduced monitoring, respectively, offset 3-5% and 15-24% of increased drug cost. Net of offsets, DOAC-related cost increases were US$258-US$464 per patient per year (PPPY) in 2015 and US$309-US$579 PPPY after market share increase. Avoided medical events offset a small portion of DOAC-related drug cost increase. NNT-based calculations provide a transparent source of budgetary-impact information for new medications.

  18. Effect of ivabradine on numbers needed to treat for the prevention of recurrent hospitalizations in heart failure patients.

    PubMed

    Rogers, Jennifer K; Kielhorn, Adrian; Borer, Jeffrey S; Ford, Ian; Pocock, Stuart J

    2015-01-01

    Ivabradine, a specific heart rate lowering agent, was shown in the SHIFT study to reduce time to first hospitalization for worsening heart failure (HF) in chronic systolic HF patients and also to reduce recurrent/total hospitalizations over the study interval. We assessed the effects of adding ivabradine in patients with systolic HF on the number needed to treat (NNT) to reduce recurrent hospitalizations. The SHIFT trial included 6505 patients with symptomatic HF (NYHA II-IV), left ventricular ejection fraction ≤35% and heart rate ≥70 bpm in sinus rhythm. Patients were randomized to either ivabradine or placebo in addition to guidelines-based drug therapy. The times to first hospitalization were analyzed using a univariate Cox proportional-hazards model; the associated NNT was calculated using Kaplan-Meier estimates of the time-to-event curves at 1 year in each treatment arm. Recurrent hospitalizations were analyzed using a negative binomial and the estimated annual event rates used to calculate the associated patient-time NNTs respectively. The estimated NNT (number needed to initiate treatment with ivabradine to prevent one first HF hospitalization within 1 year) was 27 (estimated hazard ratio: 0.75, P < 0.0001). For recurrent HF hospitalizations, one event would be prevented on average per 14 patient-years for any year of follow-up over the course of SHIFT (estimated rate ratio: 0.71, P < 0.0001). A key limitation of this analysis is that it did not account for a relationship between recurrent HF hospitalizations and subsequent mortality. In chronic systolic HF the effect of ivabradine on reducing recurrent HF hospitalizations results in a lower NNT compared to the effect on the time for first hospitalization. The effect of ivabradine on recurrent hospitalizations, in addition to first events, may be a more appropriate measure when considering the impact of a treatment with ivabradine on healthcare resource utilization.

  19. Ecological momentary assessment versus standard assessment instruments for measuring mindfulness, depressed mood, and anxiety among older adults.

    PubMed

    Moore, Raeanne C; Depp, Colin A; Wetherell, Julie Loebach; Lenze, Eric J

    2016-04-01

    As mobile data capture tools for patient-reported outcomes proliferate in clinical research, a key dimension of measure performance is sensitivity to change. This study compared performance of patient-reported measures of mindfulness, depression, and anxiety symptoms using traditional paper-and-pencil forms versus real-time, ambulatory measurement of symptoms via ecological momentary assessment (EMA). Sixty-seven emotionally distressed older adults completed paper-and-pencil measures of mindfulness, depression, and anxiety along with two weeks of identical items reported during ambulatory monitoring via EMA before and after participation in a randomized trial of Mindfulness-Based Stress Reduction (MBSR) or a health education intervention. We calculated effect sizes for these measures across both measurement approaches and estimated the Number-Needed-to-Treat (NNT) in both measurement conditions. Study outcomes greatly differed depending on which measurement method was used. When EMA was used to measure clinical symptoms, older adults who participated in the MBSR intervention had significantly higher mindfulness and significantly lower depression and anxiety than participants in the health education intervention at post-treatment. However, these significant changes in symptoms were not found when outcomes were measured with paper-and-pencil measures. The NNT for mindfulness and depression measures administered through EMA were approximately 25-50% lower than NNTs derived from paper-and-pencil administration. Sensitivity to change in anxiety was similar across administration modes. In conclusion, EMA measures of depression and mindfulness substantially outperformed paper-and-pencil measures with the same items. The additional resources associated with EMA in clinical trials would seem to be offset by its greater sensitivity to detect change in key outcome variables. Published by Elsevier Ltd.

  20. Linaclotide: promising IBS-C efficacy in an era of provisional study endpoints.

    PubMed

    Sayuk, Gregory S

    2012-11-01

    Recent disappointing developments in the pharmacotherapy of irritable bowel syndrome (IBS) have not dampened the enthusiasm surrounding linaclotide, a novel guanylate cyclase-C agonist for the management of constipation-predominant IBS (IBS-C). Two recent phase 3 studies reporting on a single, daily dose of linaclotide are presented in this issue of the American Journal of Gastroenterology. Importantly, these studies are the first to examine a provisional Food and Drug Administration (FDA) combined response endpoint for IBS-C, which mandates improvements of both abdominal pain and defecatory symptoms. Potential limitations of this FDA endpoint relate to a lack of inclusion of other potentially important IBS symptoms and an inability to directly compare findings with other recent IBS-C trials. Both studies successfully reached this endpoint in approximately one-third of study subjects, resulting in numbers needed to treat (NNT) of five to eight, to achieve an FDA responder. Individual symptom responses to linaclotide were seen in nearly 50% of participants, and potential explanations for these discrepancies when compared with the FDA endpoint are offered. Adequate relief measures also were assessed and, with NNTs of 3.4-6.8, compared favorably with other contemporary IBS-C studies. Overall, both linaclotide trials found the medication to be safe in terms of serious adverse events, though the secretagogue mechanism of action led to diarrhea in approximately one in five subjects. Together, these studies inspire several other important questions regarding linaclotide, including its role in the management of IBS-C relative to existing treatment options, such as lubiprostone. Greater clinical use of linaclotide will reveal whether the observed responses measured with the FDA provisional endpoint will translate into real-world experiences of improvement in IBS patients.

  1. The Number Needed to Treat: 25 Years of Trials and Tribulations in Clinical Research

    PubMed Central

    Suissa, Samy

    2015-01-01

    The number needed to treat (NNT) is a simple measure of a treatment’s impact, increasingly reported in randomized trials and observational studies, but often incorrectly calculated in studies involving varying follow-up times. We discuss the NNT in these contexts and illustrate the concept using several published studies. While the computation of the NNT is founded on the cumulative incidence of the outcome, several published studies use simple proportions that do not account for varying follow-up times, or use incidence rates per person-time. We show how these approaches can lead to erroneous values of the NNT and misleading interpretations. For example, a trial of 3,845 very elderly hypertensives randomized to a diuretic or placebo reported a NNT of 94 treated for 2 years to prevent one stroke, though the correct approach results in a NNT of 63. Also, meta-analyses involving trials of differing lengths often report a single NNT, such as the meta-analysis of 22 trials of the anticholinergic tiotropium in chronic obstructive pulmonary disease that reported a NNT of 16 patients “over one year,” even if the trials varied in duration from 3 to 48 months, with the actual NNTs varying widely from 15 to 250. Finally, we describe the value of the NNT in assessing benefit–risk, such as low-dose aspirin use in secondary prevention of mortality assessed against the risk of gastrointestinal bleeding. As the “number needed to treat” becomes increasingly used in the comparative effectiveness and safety of therapies, its accurate estimation and interpretation become crucial to avoid distorting clinical, economic, and public health decisions. PMID:26241223

  2. Experimental reconstruction of historical WBC measuring procedure in 1986.

    PubMed

    Vasynenko, V V; Ivanova, O M; Lytvynets, L O; Pikta, V O; Zadorozhna, G M; Chepurnyi, M I; Likhtariov, I A

    2016-12-01

    Metoiu doslidzhennia ie eksperymental'ne vidnovlennia protsedury provedennia LVL vymiriuvan' 1986 roku ta otsinka ïkh minimal'no detektovanoï aktyvnosti.Materialy i metody. Doslidzhennia buly provedeni na gamma radiometri SRP 68 01 zi stsyntyliatsiy̆nym detekto rom na osnovi krystalu NaI(Tl) ∅ 30 x 25 mm2 ta odnokanal'nomu spektrometri NC 482 VM (firmy Bicron) zi stsyntyliatsiy̆nym detektorom na osnovi krystalu NaI(Tl) ∅ 52 x 52 mm2. U roboti vykorystano zakhysnu kameru eks pertnogo lichyl'nyka vyprominiuvannia liudyny (LVL), gomogenni fantomy tila liudyny z radioaktyvnym napov niuvachem, rezul'taty LVL vymiriuvan' patsiientiv radiatsiy̆nogo reiestru (RR) NNTsRM, otrymani za dopomogoiu LVL «Skrynner ZM». V roboti vykorystano dozymetrychni ta matematychni metody.Rezul'taty ta vysnovky. Vidnovleno protseduru provedennia LVL vymiriuvan' na pryladakh, iaki vykorystovuva lys' u 1986 rotsi dlia vyznachennia vmistu inkorporovanogo radiotseziiu u naselennia RZT. Za provedenoiu otsinkoiu minimal'no detektovana aktyvnist' LVL vymiriuvan', provedenykh u 1986 rotsi, lezhyt' u mezhakh vid 1,3 kBk · or ganizm 1 (u vypadku zastosuvannia odnokanal'nogo spektrometra NC 482 VM zi stsyntyliatsiy̆nym detektorom na os novi krystalu ∅ 52 x 52 mm2) do 7,4 kBk · organizm 1 (u vypadku zastosuvannia gamma radiometra SRP 68 01 zi stsyntyliatsiy̆nym detektorom na osnovi krystalu NaI(Tl) ∅ 30 x 25 mm2) dlia dorosloï liudyny pry chasi vymiriu vannia 60 s; vid 0,8 kBk · organizm 1 do 5,6 kBk · organizm 1, vidpovidno – dlia pidlitka; ta vid 0,5 kBk · organizm 1 do 3,8 kBk · organizm 1, vidpovidno – dlia dytyny.

  3. Linaclotide: Promising IBS-C Efficacy in an Era of Provisional Study Endpoints

    PubMed Central

    Sayuk, Gregory S.

    2013-01-01

    Recent disappointing developments in the pharmacotherapy of irritable bowel syndrome (IBS) have not dampened the enthusiasm surrounding linaclotide, a novel guanylate cyclase-C agonist for the management of constipation-predominant IBS (IBS-C). Two recent phase 3 studies reporting on a single, daily dose of linaclotide are presented in this issue of the American Journal of Gastroenterology. Importantly, these studies are the first to examine a provisional Food and Drug Administration (FDA) combined response endpoint for IBS-C, which mandates improvements of both abdominal pain and defecatory symptoms. Potential limitations of this FDA endpoint relate to a lack of inclusion of other potentially important IBS symptoms and an inability to directly compare findings with other recent IBS-C trials. Both studies successfully reached this endpoint in approximately one-third of study subjects, resulting in numbers needed to treat (NNT) of five to eight, to achieve an FDA responder. Individual symptom responses to linaclotide were seen in nearly 50% of participants, and potential explanations for these discrepancies when compared with the FDA endpoint are offered. Adequate relief measures also were assessed and, with NNTs of 3.4–6.8, compared favorably with other contemporary IBS-C studies. Overall, both linaclotide trials found the medication to be safe in terms of serious adverse events, though the secretagogue mechanism of action led to diarrhea in approximately one in five subjects. Together, these studies inspire several other important questions regarding linaclotide, including its role in the management of IBS-C relative to existing treatment options, such as lubiprostone. Greater clinical use of linaclotide will reveal whether the observed responses measured with the FDA provisional endpoint will translate into real-world experiences of improvement in IBS patients. “ In seeking absolute truth we aim at the unattainable and must be content with broken portions

  4. Aspirin with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Kirthi, Varo; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine headaches. Objectives To determine the efficacy and tolerability of aspirin, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 10 March 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using aspirin to treat a discrete migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Thirteen studies (4222 participants) compared aspirin 900 mg or 1000 mg, alone or in combination with metoclopramide 10 mg, with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg. For all efficacy outcomes, all active treatments were superior to placebo, with NNTs of 8.1, 4.9 and 6.6 for 2-hour pain-free, 2-hour headache relief, and 24-hour headache relief with aspirin alone versus placebo, and 8.8, 3.3 and 6.2 with aspirin plus metoclopramide versus placebo. Sumatriptan 50 mg did not differ from aspirin alone for 2-hour pain-free and headache relief, while sumatriptan 100 mg was better than the combination of aspirin plus metoclopramide for 2-hour pain-free, but not headache relief; there were no data for 24-hour headache relief. Associated symptoms of nausea, vomiting

  5. Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression.

    PubMed

    Garneata, Liliana; Stancu, Alexandra; Dragomir, Diana; Stefan, Gabriel; Mircescu, Gabriel

    2016-07-01

    Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue-supplemented vegetarian very low-protein diet (KD) compared with conventional low-protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m(2), proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m(2) Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m(2) but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m(2) in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD. Copyright © 2016 by the American Society of Nephrology.

  6. Single dose oral ibuprofen for acute postoperative pain in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    frequent with higher doses, with 48% remedicating with 200 mg and 42% with 400 mg. The median time to remedication was 4.7 hours with 200 mg and 5.4 hours with 400 mg. Sensitivity analysis indicated that pain model and ibuprofen formulation may both affect the result, with dental impaction models and soluble ibuprofen salts producing better efficacy estimates. Adverse events were uncommon, and not different from placebo. Authors’ conclusions The very substantial amount of high quality evidence demonstrates that ibuprofen is an effective analgesic in treating postoperative pain. NNTs for 200 mg and 400 mg ibuprofen did not change significantly from the previous review even when a substantial amount of new information was added. New information is provided on remedication. PMID:19588326

  7. Recovery From Chronic Low Back Pain After Osteopathic Manipulative Treatment: A Randomized Controlled Trial.

    PubMed

    Licciardone, John C; Gatchel, Robert J; Aryal, Subhash

    2016-03-01

    Little is known about recovery after spinal manipulation in patients with low back pain (LBP). To assess recovery from chronic LBP after a short regimen of osteopathic manipulative treatment (OMT) in a responder analysis of the OSTEOPAThic Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial. A randomized double-blind, sham-controlled trial was conducted to determine the efficacy of 6 OMT sessions over 8 weeks. Recovery was assessed at week 12 using a composite measure of pain recovery (10 mm or less on a 100-mm visual analog scale) and functional recovery (2 or less on the Roland-Morris Disability Questionnaire for back-specific functioning). The RRs and numbers-needed-to-treat (NNTs) for recovery with OMT were measured, and corresponding cumulative distribution functions were plotted according to baseline LBP intensity and back-specific functioning. Multiple logistic regression was used to compute the OR for recovery with OMT while simultaneously controlling for potential confounders. Sensitivity analyses were performed to corroborate the primary results. There were 345 patients who met neither of the recovery criteria at baseline in the primary analyses and 433 patients who met neither or only 1 of these criteria in the sensitivity analyses. There was a large treatment effect for recovery with OMT (RR, 2.36; 95% CI, 1.31-4.24; P=.003), which was associated with a clinically relevant NNT (8.9; 95% CI, 5.4-25.5). This significant finding persisted after adjustment for potential confounders (OR, 2.92; 95% CI, 1.43-5.97; P=.003). There was also a significant interaction effect between OMT and comorbid depression (P=.02), indicating that patients without depression were more likely to recover from chronic LBP with OMT (RR, 3.21; 95% CI, 1.59-6.50; P<.001) (NNT, 6.5; 95% CI, 4.2-14.5). The cumulative distribution functions demonstrated optimal RR and NNT responses in patients with moderate to severe levels of LBP intensity and back-specific dysfunction at

  8. Lamotrigine for acute and chronic pain

    PubMed Central

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an update of the original Cochrane review published in Issue 2, 2007. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds five new additional studies looking at evidence for Lamotrigine as an effective treatment for acute and chronic pain. Objectives To assess analgesic efficacy and adverse effects of the antiepileptic drug lamotrigine in acute and chronic pain. Search methods Randomised controlled trials (RCTs) of lamotrigine in acute, and chronic pain (including cancer pain) were identified from MEDLINE, EMBASE and CENTRAL up to January 2011. Additional studies were sought from the reference list of the retrieved papers. Selection criteria RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of acute or chronic pain. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. Only full journal publication articles were included. Data collection and analysis Dichotomous data (ideally for the outcome of at least 50% pain relief) were used to calculate relative risk with 95% confidence intervals. Meta-analysis was undertaken using a fixed-effect model. Numbers needed to treat to benefit (NNTs) were calculated as the reciprocal of the absolute risk reduction. For unwanted effects, the NNT becomes the number needed to harm (NNH) and was calculated. Main results Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post stroke pain (1), chemotherapy induced neuropathic pain (1), diabetic neuropathy (4), HIV related neuropathy (2), mixed neuropathic pain (2), spinal cord injury related pain (1), and trigeminal neuralgia (1); none investigated lamotrigine in acute pain. The update had five additional studies (1111 additional participants). Participants were aged between 26 and 77 years. Study duration

  9. Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2014-01-01

    respectively. The numbers of participants was too small to calculate NNTs with any meaning. Authors’ conclusions The information from the single trial in acute postoperative pain suggests it to be a useful analgesic, but at doses not very different from racemic ibuprofen. PMID:19588434

  10. Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults.

    PubMed

    O'Hare, Ann M; Hotchkiss, John R; Kurella Tamura, Manjula; Larson, Eric B; Hemmelgarn, Brenda R; Batten, Adam; Do, Thy P; Covinsky, Kenneth E

    2014-03-01

    Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention. To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease. Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease. Level of estimated glomerular filtration rate (eGFR) and proteinuria. Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25. The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses. Differences in baseline risk and life expectancy between

  11. The effect of statins on cardiovascular outcomes by smoking status: A systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Ursoniu, Sorin; Mikhailidis, Dimitri P; Serban, Maria-Corina; Penson, Peter; Toth, Peter P; Ridker, Paul M; Ray, Kausik K; Kees Hovingh, G; Kastelein, John J; Hernandez, Adrian V; Manson, JoAnn E; Rysz, Jacek; Banach, Maciej

    2017-08-01

    Smoking is an important risk factor for cardiovascular disease (CVD) morbidity and mortality. The impact of statin therapy on CVD risk by smoking status has not been fully investigated. Therefore we assessed the impact of statin therapy on CVD outcomes by smoking status through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included EMBASE, ProQuest, CINAHL and PUBMED databases to 30 January 2016 to identify RCTs that investigated the effect of statin therapy on cumulative incidence of major CVD endpoints (e.g. non-fatal myocardial infarction, revascularization, unstable angina, and stroke). Relative risks (RR) ratios were calculated from the number of events in different treatment groups for both smokers and non-smokers. Finally 11 trials with 89,604 individuals were included. The number of smokers and non-smokers in the statin groups of the analyzed studies was 8826 and 36,090, respectively. The RR for major CV events was 0.73 (95% confidence interval [CI]: 0.67-0.81; p<0.001) in nonsmokers and 0.72 (95%CI: 0.64-0.81; p<0.001) in smokers. Moderate to high heterogeneity was observed both in non-smokers (I(2)=77.1%, p<0.001) and in smokers (I(2)=51.6%, p=0.024) groups. Smokers seemed to benefit slightly more from statins than non-smokers according to the number needed to treat (NNT) analysis (23.5 vs 26.8) based on RRs applied to the control event rates. The number of avoided events per 1000 individuals was 42.5 (95%CI: 28.9-54.6) in smokers and 37.3 (95%CI: 27.2-46.4) in non-smokers. In conclusion, this meta-analysis suggests that the effect of statins on CVD is similar for smokers and non-smokers, but in terms of NNTs and number of avoided events, smokers seem to benefit more although non-significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Vortioxetine for major depressive disorder: An indirect comparison with duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, using number needed to treat, number needed to harm, and likelihood to be helped or harmed.

    PubMed

    Citrome, Leslie

    2016-05-15

    Vortioxetine is approved for the treatment of major depressive disorder and differs from other antidepressants in terms of its pharmacodynamic profile. Given the limited number of head-to-head studies comparing vortioxetine with other antidepressants, indirect comparisons using effect sizes observed in other trials can be helpful to discern potential differences in clinical outcomes. Data sources were the clinical trial reports for the pivotal short-term double-blind trials for vortioxetine and from publicly available sources for the pivotal short-term double-blind trials for two commonly used generic serotonin specific reuptake inhibitor antidepressants (sertraline, escitalopram), two commonly used generic serotonin-norepinephrine reuptake inhibitor antidepressants (venlafaxine, duloxetine), and two recently introduced branded antidepressants (vilazodone, levomilnacipran). Response was the efficacy outcome of interest, defined as a≥50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale or Hamilton Depression Rating Scale. The tolerability outcome of interest was discontinuation because of an adverse event. Number needed to treat (NNT) and number needed to harm (NNH) for these outcomes vs. placebo were calculated, as well as likelihood to be helped or harmed (LHH) to contrast efficacy vs. tolerability. The analysis included 8 studies for duloxetine, 3 studies for escitalopram, 5 studies for levomilnacipran, 1 study for sertraline, 4 studies for venlafaxine, 2 studies for vilazodone, and 11 studies for vortioxetine. NNTs for response vs. placebo were 6 (95% CI 5-8), 7 (5-11), 10 (8-16), 6 (4-13), 6 (5-9), 8 (6-16), and 9 (7-11), respectively. NNHs for discontinuation because of an adverse event vs. placebo were 25 (17-51), 31 (19-92), 19 (14-27), 7 (5-12), 8 (7-11), 27 (15-104), and 43 (28-91), respectively. LHH values contrasting response vs. discontinuation because of an adverse event were 4.3, 4.6, 1.8, 1.2, 1.4, 3.3, and 5.1 respectively

  13. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting Objectives To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6

  14. Single dose oral analgesics for acute postoperative pain in adults.

    PubMed

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2011-09-07

    , fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions.NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids.Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg.Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

  15. Single dose oral analgesics for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2014-01-01

    mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids. Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg. Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. Authors’ conclusions There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias

  16. Single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

    PubMed

    Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

    2015-09-28

    , methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence). There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can

  17. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults

    PubMed Central

    Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on ‘Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain’. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. Objectives To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Main results Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at

  18. Gabapentin for chronic neuropathic pain and fibromyalgia in adults

    PubMed Central

    Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. Objectives To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. Search methods We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. Selection criteria Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. Data collection and analysis Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMM-PACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. Main results Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with

  19. Topical NSAIDs for chronic musculoskeletal pain in adults

    PubMed Central

    Derry, Sheena; Moore, R Andrew; Rabbie, Roy

    2014-01-01

    compared a topical NSAID with placebo. Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions. The best data were for topical diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8 to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel formulation. There were too few data of good quality to calculate NNTs for other individual topical NSAIDs compared with placebo. Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy. There was an increase in local adverse events (mostly mild skin reactions) with topical NSAIDs compared with placebo or oral NSAIDs, but no increase in serious adverse events. Gastrointestinal adverse events with topical NSAID did not differ from placebo, but were less frequent than with oral NSAIDs. A substantial amount of data from unpublished studies was unavailable. Much of this probably relates to formulations that have never been marketed. Authors’ conclusions Topical NSAIDs can provide good levels of pain relief; topical diclofenac solution is equivalent to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence for other chronic painful conditions. Formulation can influence efficacy. The incidence of local adverse events is increased with topical NSAIDs, but gastrointestinal adverse events are reduced compared with oral NSAIDs. PMID:22972108

  20. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder

    PubMed Central

    Kane, John M.; Correll, Christoph U.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

    2017-01-01

    Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO

  1. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder.

    PubMed

    Kane, John M; Correll, Christoph U; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

    2017-08-01

    Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO, 3.2), Week 48 (80 mg, 2.2; 40 mg, 2

  2. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder.

    PubMed

    Correll, Christoph U; Josiassen, Richard C; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

    2017-08-01

    Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40 mg, 2.9, d = 0.39; PBO, 3.2), Week 48

  3. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder

    PubMed Central

    Correll, Christoph U.; Josiassen, Richard C.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

    2017-01-01

    Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40

  4. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

    PubMed Central

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo. Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups. Authors’ conclusions This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information. PMID:19160199

  5. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults.

    PubMed

    Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew

    2008-10-08

    This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on 'Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain'. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. Area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 500 mg

  6. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults.

    PubMed

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2009-01-21

    This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Two authors assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus

  7. Diclofenac with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Derry, Sheena; Rabbie, Roy; Moore, R Andrew

    2014-01-01

    potassium 50 mg versus placebo (two studies), the NNTs were 6.2, 8.9, and 9.5 for pain-free at two hours, headache relief at two hours, and pain-free responses at 24 hours, respectively. Associated symptoms of nausea, photophobia and phonophobia, and functional disability were reduced within two hours, and similar numbers of participants experienced adverse events, which were mostly mild and transient. There were insufficient data to evaluate other doses of oral diclofenac, or to compare different formulations or different dosing regimens; only one study compared oral diclofenac with an active comparator (oral sumatriptan 100 mg). Authors’ conclusions Oral diclofenac potassium 50 mg is an effective treatment for acute migraine, providing relief from pain and associated symptoms, although only a minority of patients experience pain-free responses. Adverse events are mostly mild and transient and occur at the same rate as with placebo. PMID:22336852

  8. Topical NSAIDs for acute musculoskeletal pain in adults.

    PubMed

    Derry, Sheena; Moore, R Andrew; Gaskell, Helen; McIntyre, Mairead; Wiffen, Philip J

    2015-06-11

    , and 220 with an oral NSAID. This was a 63% increase in the number of included participants over the previous version of this review. We also identified a number of studies in clinical trial registries with unavailable results amounting to about 5900 participants for efficacy and 5300 for adverse events.Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin demonstrated significantly higher rates of clinical success (more participants with at least 50% pain relief) than matching topical placebo (moderate or high quality data). Benzydamine did not. Three drug and formulation combinations had NNTs for clinical success below 4. For diclofenac, the Emulgel® formulation had the lowest NNT of 1.8 (95% CI 1.5 to 2.1) in two studies using at least 50% pain intensity reduction as the outcome. Diclofenac plasters other than Flector® also had a low NNT of 3.2 (2.6 to 4.2) based on good or excellent responses in some studies. Ketoprofen gel had an NNT of 2.5 (2.0 to 3.4), from five studies in the 1980s, some with less well defined outcomes. Ibuprofen gel had an NNT of 3.9 (2.7 to 6.7) from two studies with outcomes of marked improvement or complete remission. All other drug and formulation combinations had NNT values above 4, indicating lesser efficacy.There were insufficient data to compare reliably individual topical NSAIDs with each other or the same oral NSAID.Local skin reactions were generally mild and transient, and did not differ from placebo (high quality data). There were very few systemic adverse events (high quality data) or withdrawals due to adverse events (low quality data). Topical NSAIDs provided good levels of pain relief in acute conditions such as sprains, strains and overuse injuries, probably similar to that provided by oral NSAIDs. Gel formulations of diclofenac (as Emugel®), ibuprofen, and ketoprofen, and some diclofenac patches, provided the best effects. Adverse events were usually minimal.Since the last version of this

  9. Topical capsaicin (high concentration) for chronic neuropathic pain in adults.

    PubMed

    Derry, Sheena; Rice, Andrew Sc; Cole, Peter; Tan, Toni; Moore, R Andrew

    2017-01-13

    single drug application were from the Patient Global Impression of Change (PGIC) at specific points, usually 8 and 12 weeks. We also assessed average pain scores over weeks 2 to 8 and 2 to 12 and the number of participants with pain intensity reduction of at least 30% or at least 50% over baseline, and information on adverse events and withdrawals.We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data.For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo, with point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) of 8.8 (95% confidence interval (CI) 5.3 to 26) with high-concentration capsaicin and 7.0 (95% CI 4.6 to 15) with 'active' placebo (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence).For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more

  10. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews.

    PubMed

    Derry, Sheena; Wiffen, Philip J; Kalso, Eija A; Bell, Rae F; Aldington, Dominic; Phillips, Tudor; Gaskell, Helen; Moore, R Andrew

    2017-05-12

    ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.