Background: Despite the abundant literature on this topic, accurate prevalence estimates of pain in cancer patients are not available. We investigated the prevalence of pain in cancer patients ...according to the different disease stages and types of cancer. Patients and methods: A systematic review of the literature was conducted. An instrument especially designed for judging prevalence studies on their methodological quality was used. Methodologically acceptable articles were used in the meta-analyses. Results: Fifty-two studies were used in the meta-analysis. Pooled prevalence rates of pain were calculated for four subgroups: (i) studies including patients after curative treatment, 33% 95% confidence interval (CI) 21% to 46%; (ii) studies including patients under anticancer treatment: 59% (CI 44% to 73%); (iii) studies including patients characterised as advanced/metastatic/terminal disease, 64% (CI 58% to 69%) and (iii) studies including patients at all disease stages, 53% (CI 43% to 63%). Of the patients with pain more than one-third graded their pain as moderate or severe. Pooled prevalence of pain was >50% in all cancer types with the highest prevalence in head/neck cancer patients (70%; 95% CI 51% to 88%). Conclusion: Despite the clear World Health Organisation recommendations, cancer pain still is a major problem.
Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock ...hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia.
In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged mean±standard deviation 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism n=1269, prediabetes n=335, or T2DM n=609). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease.
Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 -0.97 to -0.25) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 -163 to 72) with further deterioration in T2DM (B=-184 -297 to -71) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 -0.15 to -0.05, P<0.001 and standardized B=-0.13 -0.19 to -0.07, P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 -0.15 to -0.04, P<0.001 and standardized B=-0.10 -0.15 to -0.04, P=0.002, respectively).
Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.
By using a population-based cohort of the general Dutch population, the authors studied whether an excessively negative orientation toward pain (pain catastrophizing) and fear of movement/(re)injury ...(kinesiophobia) are important in the etiology of chronic low back pain and associated disability, as clinical studies have suggested. A total of 1,845 of the 2,338 inhabitants (without severe disease) aged 25–64 years who participated in a 1998 population-based questionnaire survey on musculoskeletal pain were sent a second questionnaire after 6 months; 1,571 (85 percent) participated. For subjects with low back pain at baseline, a high level of pain catastrophizing predicted low back pain at follow-up (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.0, 2.8) and chronic low back pain (OR = 1.7, 95% CI: 1.0, 2.3), in particular severe low back pain (OR = 3.0, 95% CI: 1.7, 5.2) and low back pain with disability (OR = 3.0, 95% CI: 1.7, 5.4). A high level of kinesiophobia showed similar associations. The significant associations remained after adjustment for pain duration, pain severity, or disability at baseline. For those without low back pain at baseline, a high level of pain catastrophizing or kinesiophobia predicted low back pain with disability during follow-up. These cognitive and emotional factors should be considered when prevention programs are developed for chronic low back pain and related disability.
Summary Background In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin ...is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduction are scarce. We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units (ICUs) in a health-care system with a comparatively low use of antibiotics. Methods We did a prospective, multicentre, randomised, controlled, open-label intervention trial in 15 hospitals in the Netherlands. Critically ill patients aged at least 18 years, admitted to the ICU, and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate. Patients who received antibiotics for presumed infection were randomly assigned (1:1), using a computer-generated list, and stratified (according to treatment centre, whether infection was acquired before or during ICU stay, and dependent on severity of infection ie, sepsis, severe sepsis, or septic shock) to receive either procalcitonin-guided or standard-of-care antibiotic discontinuation. Both patients and investigators were aware of group assignment. In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0·5 μg/L or lower. In the standard-of-care group, patients were treated according to local antibiotic protocols. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment. All analyses were done by intention to treat. Mortality analyses were completed for all patients (intention to treat) and for patients in whom antibiotics were stopped while being on the ICU (per-protocol analysis). Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules (per-protocol analysis). The study is registered with ClinicalTrials.gov , number NCT01139489 , and was completed in August, 2014. Findings Between Sept 18, 2009, and July 1, 2013, 1575 of the 4507 patients assessed for eligibility were randomly assigned to the procalcitonin-guided group (761) or to standard-of-care (785). In 538 patients (71%) in the procalcitonin-guided group antibiotics were discontinued in the ICU. Median consumption of antibiotics was 7·5 daily defined doses (IQR 4·0–12·7) in the procalcitonin-guided group versus 9·3 daily defined doses (5·0–16·6) in the standard-of-care group (between-group absolute difference 2·69, 95% CI 1·26–4·12, p<0·0001). Median duration of treatment was 5 days (3–9) in the procalcitonin-guided group and 7 days (4–11) in the standard-of-care group (between-group absolute difference 1·22, 0·65–1·78, p<0·0001). Mortality at 28 days was 149 (20%) of 761 patients in the procalcitonin-guided group and 196 (25%) of 785 patients in the standard-of-care group (between-group absolute difference 5·4%, 95% CI 1·2–9·5, p=0·0122) according to the intention-to-treat analysis, and 107 (20%) of 538 patients in the procalcitonin-guided group versus 121 (27%) of 457 patients in the standard-of-care group (between-group absolute difference 6·6%, 1·3–11·9, p=0·0154) in the per-protocol analysis. 1-year mortality in the per-protocol analysis was 191 (36%) of 538 patients in the procalcitonin-guided and 196 (43%) of 457 patients in the standard-of-care groups (between-group absolute difference 7·4, 1·3–13·8, p=0·0188). Interpretation Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection. This reduction was associated with a significant decrease in mortality. Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship. Funding Thermo Fisher Scientific.
Purpose
To investigate central and peripheral corneal endothelial cell density (ECD) in relation to Baerveldt (BV) glaucoma drainage device (GDD) tube corneal (TC) distance.
Methods
Prospective study ...of all patients scheduled for glaucoma tube surgery with 36 months follow‐up. A BV GDD was inserted into the anterior chamber (AC). Anterior segment optical coherence tomography (AS‐OCT) scans were made to determine the TC distance. Central and peripheral ECD was measured, preoperatively and at 3, 6, 12, 24 and 36 months postoperatively.
Results
Fifty‐three eyes were included primary open‐angle glaucoma, (n = 13); secondary glaucoma, (n = 30); and primary angle‐closure glaucoma, (n = 10). Central ECD significantly decreased during follow‐up, with a mean decrease of 4.54% per year (p < 0.001), and 6.57% in the peripheral quadrant closest to the BV GDD tube (PQC, p < 0.001). In the PQC, a yearly decrease of 1.57% was shown after transiridial tube placement versus 7.43% after placement ‘free’ into the AC (p = 0.006). Endothelial cell (EC) loss was related to TC distance (mean 1.69 mm), with a central loss of 6.20% and 7.25% in the PQC per year with shorter TC distances, versus a central loss of 4.11% and 5.77% in the PQC per year with longer TC distances (outside mean ± 2SD, p < 0.001). A difference in EC loss by glaucoma subtype was not identified.
Conclusion
The TC distance is of significant influence on corneal ECD, a shorter TC distance causing more severe EC loss, especially in the PQC. Transiridial placement of the BV GDD tube seems safer than placement ‘free’ into the AC.
Purpose To evaluate the optimum medical strategy to prevent cystoid macular edema (CME) after cataract surgery. Design Systematic review and meta-analysis. Methods setting : Cochrane, MEDLINE, and ...EMBASE databases were searched to identify eligible randomized controlled trials (RCTs). study population : RCTs comparing medical strategies to prevent CME after uncomplicated cataract surgery in nondiabetic and diabetic patients. observation procedures : Data were extracted by 2 authors independently. Quality of individual RCTs was assessed using the Cochrane Collaboration's tool for assessing risk of bias and Delphi criteria. main outcome measures : Odds of developing CME within 3 months postoperatively and foveal thickness, macular volume and corrected distance visual acuity change within 3 months postoperatively, as compared to baseline. Results Seventeen trials reported incidence rates. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduced the odds of developing CME as compared to topical corticosteroids in nondiabetic (odds ratio OR 0.11; 95% confidence interval 95% CI 0.03–0.37) and mixed populations (OR 0.05; 95% CI 0.02–0.11). A combination of topical corticosteroids and NSAIDs significantly reduced the odds of developing CME as compared to topical corticosteroids in nondiabetic (OR 0.21; 95% CI 0.10–0.44) and diabetic patients (OR 0.17; 95% CI 0.05–0.50). Intravitreal corticosteroid or anti–vascular endothelial growth factor injections did not show any additional benefit in diabetic subjects. Conclusions Topical NSAIDs significantly reduced the odds of developing CME, as compared to topical corticosteroids, in nondiabetic and mixed populations. A combination of topical NSAIDs and corticosteroids reduced the odds of developing CME in nondiabetic and diabetic patients, as compared to topical corticosteroids.
Optical coherence tomography (OCT) of the retina and around the optic nerve head and corneal confocal microscopy (CCM) are non-invasive and repeatable techniques that can quantify ocular ...neurodegenerative changes in individuals with diabetes. We systematically reviewed studies of ocular neurodegenerative changes in adults with type 1 or type 2 diabetes and noted changes in the retina, the optic nerve head, and the cornea. Of the 30 studies that met our inclusion criteria, 14 used OCT and 16 used CCM to assess ocular neurodegenerative changes. Even in the absence of diabetic retinopathy, several layers in the retina and the mean retinal nerve fibre layer around the optic nerve head were significantly thinner (-5·36 μm 95% CI -7·13 to -3·58) in individuals with type 2 diabetes compared with individuals without diabetes. In individuals with type 1 diabetes without retinopathy none of the intraretinal layer thicknesses were significantly reduced compared with individuals without diabetes. In the absence of diabetic polyneuropathy, individuals with type 2 diabetes had a lower nerve density (nerve branch density: -1·10/mm(2) 95% CI -4·22 to 2·02), nerve fibre density: -5·80/mm(2) -8·06 to -3·54, and nerve fibre length: -4·00 mm/mm(2) -5·93 to -2·07) in the subbasal nerve plexus of the cornea than individuals without diabetes. Individuals with type 1 diabetes without polyneuropathy also had a lower nerve density (nerve branch density: -7·74/mm(2) 95% CI -14·13 to -1·34, nerve fibre density: -2·68/mm(2) -5·56 to 0·20), and nerve fibre length: -2·58 mm/mm(2) -3·94 to -1·21). Ocular neurodegenerative changes are more evident when diabetic retinopathy or polyneuropathy is present. OCT and CCM are potentially useful, in addition to conventional clinical methods, to assess diabetic neurodegenerative changes. Additional research is needed to determine their incremental benefit and to standardise procedures before the application of OCT and CCM in daily practice.
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
Background
Studies of see‐and‐treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates.
Objectives
To determine ...overtreatment rates in see‐and‐treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see‐and‐treat management.
Search strategy
MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014.
Selection criteria
Studies of see‐and‐treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included.
Data collection and analysis
Methodological quality was assessed with the Newcastle–Ottawa scale. We used the inverse variance method for pooling incidences, and a random‐effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1.
Main results
Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high‐grade cervical smear and a high‐grade colposcopic impression was 11.6% (95% CI 7.8–15.3%). The overtreatment rate in women with a high‐grade cervical smear and low‐grade colposcopic impression was 29.3% (95% CI 16.7–41.9%), and in the case of a low‐grade smear and high‐grade colposcopic impression it was 46.4% (95% CI 15.7–77.1%). In women with a low‐grade smear and low‐grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1–77.7%).
Author's conclusions
The pooled overtreatment rate in women with a high‐grade smear and high‐grade colposcopic impression is at least comparable with the two‐step procedure, which supports the use of see‐and‐treat management in this subgroup of women.
Tweetable
See‐and‐treat management is justified in the case of a high‐grade smear and a high‐grade colposcopic impression.
Tweetable
See‐and‐treat management is justified in the case of a high‐grade smear and a high‐grade colposcopic impression.
Retinopathy and neuropathy in type 2 diabetes are preceded by retinal nerve fibre layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), ...measures of glycaemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance. We used cross-sectional data from The Maastricht Study (up to 5455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycaemia (fasting plasma glucose FPG, 2-h post-load glucose 2-h PG, HbA1c, advanced glycation endproducts AGEs assessed as skin autofluorescence SAF) and indices of daily GV (incremental glucose peak IGP and continuous glucose monitoring CGM-assessed standard deviation SD) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycaemia. After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta 95% CI, respectively - 0.16 - 0.25; - 0.08; - 0.05 - 0.13; 0.03; P
= 0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP, but not CGM-assessed SD, were also associated with lower RNFL thickness (per SD, respectively - 0.05 - 0.08; - 0.01; - 0.06 - 0.09; - 0.02; - 0.05 - 0.08; - 0.02; - 0.04 - 0.07; - 0.01; - 0.06 - 0.12; - 0.01; and - 0.07 - 0.21; 0.07). In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycaemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycaemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of retinopathy and neuropathy.
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