Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of ...neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies ( r2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.
Summary Background Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but ...evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms. Methods We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035. Findings 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score POP-SS) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3·77 SD 5·62 vs 2·09 5·39; adjusted difference 1·52, 95% CI 0·46–2·59; p=0·0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study. Interpretation One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups. Funding Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia).
To assess the 3-month and 12-month postoperative visual performance and subjective patient satisfaction after refractive lens exchange (RLE) with implantation of a rotationally asymmetric multifocal ...intraocular lens (IOL).
Cathedral Eye Clinic, Belfast, United Kingdom.
Prospective case series.
The refraction, uncorrected (UDVA) and corrected distance visual acuities, uncorrected intermediate (UIVA) and near (UNVA) visual acuities, distance-corrected intermediate and near visual acuities, and a quality of vision (QoV) questionnaire were evaluated 3 months and 12 months after implantation of an SBL-3 IOL.
The study enrolled 100 eyes of 50 patients. The mean monocular UDVA was -0.02 logarithm of minimum angle of resolution (logMAR) ± 0.12 (SD) 3 months postoperatively and -0.01 ± 0.10 logMAR at 12 months (P = .393). The mean monocular UIVA was 0.39 ± 0.11 logMAR and 0.41 ± 0.12 logMAR, respectively (P = .06). The mean monocular UNVA was 0.12 ± 0.13 logMAR and 0.14 ± 0.12 logMAR, respectively (P = .077). The mean QoV score was 8.26 ± 1.16 at 3 months with a significant improvement at 12 months, at which time the mean QoV score was 8.84 ± 1.08 (P ≤ .001).
This asymmetric multifocal IOL provided excellent unaided vision with no significant difference in near, intermediate, and distance vision 3 months and 12 months postoperatively. However, there was a significant improvement in subjective outcomes at the second postoperative assessment, during which patients reported a significantly better QoV score and less blurred vision.
Summary Background Growth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of ...stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identification of effective interventions remains a challenge. Methods We analysed the effect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defined growth faltering as fall in Z score between 3 months and 21 months of age. Findings We noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5–44·0) for underweight and 57·1% (51·9–62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score −1·36, 95% CI −1·44 to −1·27, weight-for-age Z score −1·20, −1·28 to −1·11, and head circumference Z score −0·51, −0·59 to −0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0–33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight). Interpretation A combination of nutrition-sensitive and nutrition-specific interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions. Funding UK Medical Research Council, UK Department for International Development.
A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential ...accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease.
The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration.
Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration.
We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.
Introduction Despite known benefits of regular physical activity (PA), residents of low-income communities have disproportionately high rates of physical inactivity. Mounting evidence suggests that ...social network characteristics may be associated with health behaviors, including PA. The purpose of the current study was to examine associations between egocentric network characteristics and meeting PA guidelines among residents of low-income and predominantly African-American communities. Methods Data from the Greenville Healthy Neighborhoods Project (2014), a cross-sectional study, examined social network characteristics, including the PA behavior of social ties, and whether participants met PA guidelines (150 minutes per week of aerobic exercise). Respondent-driven sampling (non-random) was utilized to recruit participants ( n =430) within eight low-income communities. Logistic regression analyses, performed in 2016, included robust sandwich estimation to account for clustering (non-independence) of observations. Results Participants were predominantly older (M=54.4 years, SD=15.1 years), African American (88.0%), and female (70.7%). More than one third of participants had an annual household income <$15,000 (41.6%) or reported meeting the current aerobic PA guidelines (45.8%). Controlling for sociodemographic characteristics, greater network extensity (based on the occupation of ego’s network ties; OR=1.11, 95% CI=1.03, 1.20, p =0.02) and a higher percentage of physically active network members (OR=1.97, 95% CI=1.02, 3.82, p =0.04) were associated with higher odds of meeting PA guidelines. Conclusions Social network characteristics are associated with individual PA behavior among residents of low-income communities. Interventions to increase PA among low-income and predominantly African-American communities should leverage personal networks, including the implementation of walking groups or buddy systems.
WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory ...hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron.
We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18–45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation UNIMMAP containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14–18 weeks vs 19–22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at −5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180.
Between June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was −2·2 g/L (95% CI −4·6 to 0·1) with the 60 mg screen-and-treat approach and −2·7 g/L (–5·0 to −0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study.
The hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought.
Bill & Melinda Gates Foundation and the UK Medical Research Council.
To determine the degree of tolerance toward different magnitudes of residual refractive astigmatism and corneal astigmatism and the angles of corneal astigmatism after implantation of an asymmetric ...multifocal intraocular lens (IOL).
Cathedral Eye Clinic, Belfast, United Kingdom.
Retrospective comparative case series.
The study enrolled patients having refractive lens exchange and implantation of a Lentis Mplus LS-312 MF30 IOL. Uncorrected (UDVA) and corrected distance visual acuities, uncorrected near and intermediate visual acuities, and quality-of-vision questionnaires were evaluated. Groups were categorized based on the magnitude of refractive astigmatism and corneal residual astigmatism. Refractive astigmatism of less than 0.50 diopter (D) and more than 0.50 D and corneal astigmatism of 0.50 D or less, 0.51 to 0.75 D, 0.76 to 1.00 D, and more than 1.00 D were categorized.
The study comprised 117 patients (234 eyes). There was a significant difference in UDVA (P = .003), refractive sphere (P = .001), and defocus equivalent (P ≤ .001) between the residual refractive astigmatism groups; however, there was no difference in quality of vision (P = .28). The same was found for corneal astigmatism with UDVA (P ≤ .001) and quality of vision (P = .16). The angle of corneal astigmatism in relation to IOL placement did not statistically affect postoperative outcomes.
The IOL appeared to subjectively tolerate residual astigmatism well despite a statistically significant difference in UDVA with higher magnitudes of residual astigmatism. The angle of residual corneal astigmatism in relation to IOL placement did not have a significant effect on postoperative outcomes.
None of the authors has a financial or proprietary interest in any material or method mentioned.
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