The effect and implementation of the COVID Box, a remote patient monitoring system for patients with a COVID-19 infection in primary care: a matched cohort study.

At the onset of the COVID-19 pandemic, the pressure on hospitals increased tremendously. To alleviate this pressure, a remote patient monitoring system called the COVID Box was developed and implemented in primary care. The aim was to assess whether the COVID Box in primary care could reduce emergency department (ED) referrals due to a COVID-19 infection. A matched cohort study was performed between December 2020 and June 2021. Patients with a COVID-19 infection in need of intensive monitoring based on the clinical judgement of their own general practitioner received the COVID Box in primary care combining home monitoring of vital parameters with daily video consultations. The control group was retrospectively matched by propensity score matching. We conducted a subgroup analysis in higher-risk patients with oxygen saturation measurements, considering oxygen saturation as a critical parameter for assessing the risk of a complicated infection. We included 205 patients, of whom 41 patients were monitored with the COVID Box (mean age 70 and 53.7% male) and 164 in the control group (mean age 71.5 and 53% male). No difference was found in ED referrals between the intervention and control groups in our primary analysis. In the subgroup analysis, we found a nonsignificant trend that remote monitoring could reduce the ED referrals. While the overall study found comparable ED referrals between groups, the subgroup analysis suggested a promising prospect in reducing ED referrals due to remote monitoring of higher-risk patients with acute respiratory disease in primary care.

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

Patients' Use of the Internet to Find Reliable Medical Information About Minor Ailments: Vignette-Based Experimental Study.

BACKGROUND: Little is known about the exact process of how patients search for medical information on the internet and what they retrieve. There is especially a paucity of literature on browsing for information on minor ailments, a term used for harmless diseases that are very common in the general population and thus have a significant impact on health care. OBJECTIVE: This vignette-based experimental study aimed to explore what kind of Web-based search strategies are applied and how search strategies, demographic characteristics, and the quality of the visited websites relate to finding the right diagnosis. Additional goals were to describe how searching on the Web influences one's perception of the severity of the potential diagnosis and whether or not the participants would discuss the information they found on the internet with their doctors. METHODS: Out of 1372 survey participants, 355 were randomly sampled, and 155 of them were recruited and assigned to one of four clinical scenarios. Each search term they used was classified as one of three search strategies: (1) hypothesis testing, (2) narrowing within the general hypothesis area, and (3) symptom exploration. The quality of the websites used was determined by using the DISCERN instrument. To compare the diagnostic accuracy of the participants before and after the internet search, a McNemar test was used. Chi-square tests were used to describe which factors are related to the chosen search strategy. A multivariate binary logistic regression model was constructed to predict which factors are related to finding a sound diagnosis after searching the internet for health information. RESULTS: Most participants (65.8%, 102/155) used the symptom exploration strategy. However, this depends on the assigned scenario (P<.001) and the self-estimated severity score of the symptoms before the internet search (P=.001). A significant relation was found between choosing an accurate diagnosis and age (odds ratio [OR] 0.94, 95% CI 0.90 to 0.98) and the clinical scenario, as well as the use of high-quality websites (OR 7.49, 95% CI 1.85 to 30.26). Browsing the internet did not lead to a statistically significant change in participants' beliefs about the severity of the condition (McNemar test, P=.85). Most participants (65%) shared their retrieved information with their physician and most of them (75%) received a positive response. CONCLUSIONS: Our findings suggest that most patients use a symptom-based approach; however, if patients expect the potential diagnosis to be severe, they tend to use a hypothesis verification strategy more often and are therefore prone to certain forms of bias. In addition, self-diagnosing accuracy is related to younger age, the symptom scenario, and the use of high-quality websites. We should find ways to guide patients toward search strategies and websites that may more likely lead to accurate decision making.

Estimation of relative economic weights and the marginal willingness to pay for breeding traits of Brown Swiss cattle using discrete choice experiments.

Breeding traits are usually combined in a total merit index according to their economic weights to maximize genetic gain based on economic merit. However, this maximization may not always be the aim of the selection decisions by farm managers. A discrete choice experiment was used to evaluate the importance of traits in terms of the selection decisions of farm managers operating in different environments. Six trait complexes, the semen price, the interactions between these traits, and significant characteristics of the farms were included in a conditional logit model to estimate relative economic weights and the marginal willingness to pay for all traits. Milk value, conformation/udder, and fitness were the most important traits for the farmers, and significant interactions indicated that fitness is of greater importance on organically managed farms than on conventional farms. Farm managers with an advanced education placed more weight on the milk value trait than farm managers without advanced education. On conventional farms, managers weighted the traits milk value and conformation/udder highly. The conformation/udder and fitness trait complexes were important on organic farms. A new trait called perinatal sucking behavior of newborn calves should be included in the total merit index.

The Reliability of Sensor-Assisted Soft Tissue Measurements in Primary Total Knee Arthroplasty.

BACKGROUND: In pursuit to improve soft tissue balancing in total knee arthroplasties (TKAs), a wireless device was introduced to assess femorotibial pressures. The aim of this study was to evaluate the reliability of this device. METHODS: After 33 TKAs were balanced by conventional techniques, contact pressures were measured using a wireless sensor 3 times in a row; twice while the examiner was blinded for the result (n = 29); and once while the examiner was able to see the result as visual feedback (n = 32). Femorotibial pressures were measured in the medial and lateral compartments with the knee in 10°, 45°, and 90° of flexion (6 measurements per TKA). Furthermore, both the combined pressure and the difference in pressure between the compartments was calculated throughout the 3 positions (together another 6 measurements per TKA). RESULTS: The intraclass correlation coefficient between the blind measurements was poor in 2 of the 12 (17%), moderate in 4 of 12 (33%), and good in 6 of 12 (50%) measurements. The intraclass correlation coefficient between the blind and observing measurement was poor in 2 of the 12 (17%), moderate in 6 of 12 (50%), and good in 4 of 12 (33%) measurements. Especially measurements in 10° of flexion are associated with poorer reliability. CONCLUSION: The wireless sensor has a moderate to good reliability in 83% of the measurements.

Surgical Versus Nonoperative Treatment in Patients Up to 18 Years Old With Traumatic Shoulder Instability: A Systematic Review and Quantitative Synthesis of the Literature.

PURPOSE: To compare the outcome of surgical and nonoperative treatment in patients aged 18 years or younger with traumatic shoulder instability. METHODS: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. A complete search of PubMed, Medline, Cochrane, CINAHL, Embase, and Google Scholar databases was performed using various combinations of the keywords "shoulder," "instability," "glenohumeral instability," "pediatric," "adolescent," "skeletally immature," "young," "open physis," "children," "management," "treatment," "surgical," "stabilization," and "recurrence." There was no time restriction. RESULTS: Fifteen articles met our inclusion criteria, including a total of 693 patients with 705 shoulders aged 18 years or younger. Of 411 shoulders, 293 (71.3%) treated with a nonoperative approach experienced a redislocation compared with 55 of 314 shoulders (17.5%) that received surgical treatment. The results of the quantitative synthesis showed that the recurrence rate was significantly lower in the surgical group compared with the nonoperative group. CONCLUSIONS: The recurrence rate is lower in patients undergoing surgical treatment. Further studies are necessary to clarify several points in the treatment of skeletally immature patients with traumatic shoulder instability. LEVEL OF EVIDENCE: Level III, systematic review of Level II and III studies and 1 case series.

Redislocation risk after an arthroscopic Bankart procedure in collision athletes: a systematic review.

BACKGROUND: The purpose of this review was to determine the redislocation risk for collision athletes after an arthroscopic Bankart repair and to compare the redislocation rate between collision athletes and noncollision athletes after an arthroscopic Bankart repair. METHODS: A PubMed and Embase query was performed, screening all relevant literature of arthroscopic Bankart procedures mentioning redislocation rates in collision athletes. Studies with a follow-up <2 years or lacking information on redislocation rates in collision athletes were excluded. We used the modified Coleman Methodology Score to assess the quality of included studies. Finally, the data in all the studies were combined and analyzed. RESULTS: There were 1012 studies screened on title and abstract, of which 111 studies were full-text screened, and finally 20 studies were included. Four studies reported on collision athletes only, whereas 16 compared collision with noncollision athletes. Fourteen studies reported increased redislocation rates for collision athletes in comparison to noncollision athletes (absolute risk difference varying from 0.4% to 28.6%), whereas 2 studies reported decreased rates (absolute risk differences of -6% and -2.4%). A combined analysis revealed that collision athletes have an increased absolute risk of 8.09 with 95% CI from 3.61 to 12.57% for development of postoperative instability in comparison to noncollision athletes (P = .001). CONCLUSION: Collision athletes have an increased risk for redislocation in comparison to noncollision athletes after an arthroscopic Bankart repair, although there were no differences in return to sport.

[Influence of Macular Hole Width on Visual Acuity, Endotamponade and Closure Rate]. / Einfluss der Lochbreite auf Visus, Endotamponade und Verschlussrate beim Makulaforamen.

Background: The influence of the width of a full-thickness macular hole on preoperative visual acuity and its role for the intraoperative approach and closure rate were analysed in a prospective study. Methods: For 47 patients with a full thickness macular hole, a precise analysis of the central retina was performed with SD-OCT. An SF6-gas-air mixture was used, with a lower concentration (15 %) for smaller holes ≤ 400 µm (group 1, n = 17) and a higher concentration (30 %) for larger holes > 400 µm (group 2, n = 30). Besides preoperative visual acuity, postoperative IOP fluctuations and closure rate were reviewed. Results: The mean hole width with SD-OCT was 419 ± 155 µm, with a significant negative correlation with preoperative visual acuity (r = - 0.56, p = 0.002). In the first group, mean early postoperative IOP was 23 mmHg and in the second group 33 mmHg (p < 0.001). Thus, for small macular holes, early postoperative IOP decompensation from gas expansion in the eye could be minimised. The closure rate was 90 %, with no significant difference between the two groups (p > 0.05). Conclusion: Determining the width of a macular hole with SD-OCT is an important indicator for the necessary endotamponade. Using a lower gas concentration (15 %) for smaller holes (≤ 400 µm) to prevent postoperative IOP fluctuations does not negatively influence closure rates.

[Relevant Parameters of Optic Nerve Analysis from Spectral Domain OCT for Glaucoma Diagnostics]. / Relevante Parameter der Papillenanalyse mittels Spectral-Domain-OCT zur Glaukomdiagnostik.

BACKGROUND: In early diagnosis and follow-up of patients with glaucoma anatomic-diagnostic examinations have become more important in addition to static perimetry. Patients with open angle glaucoma suffer a slow visual field loss due to the loss of ganglion cells, which these examinations could detect earlier than perimetry can. METHODS: Parameters of the optical coherence tomography (OCT) were analysed in 89 patients (175 eyes) with advanced open angle glaucoma. In a prospective study, the functional findings from static perimetry (HFA-II, 24-2-programme) and the anatomic parameters of optic nerve analysis with SD-OCT (Cirrus-OCT) were evaluated. RESULTS: The results showed a mean deviation (MD) in perimetry of - 8.31 ± 9.76 dB and in the analysis of the optic nerve head of 71.93 ± 15.86 µm retinal nerve fibre layer (RNFL) as well as 85.54 ± 28.2 µm RNFL for the inferior quadrant, 0.95 ± 0.46 mm(2) for the rim area and 0.69 ± 0.18 for the vertical CD ratio. There was a significant correlation (p < 0.05) between MD und RNFL (r = 0.603), as well as RNFL of the inferior quadrant (r = 0.620), rim area (r = 0.552) and average CD ratio (r = - 0.551). The best correlation for the optical nerve head analysis was found between MD and vertical CD ratio (r = - 0.568). CONCLUSIONS: There was a good correlation between functional and anatomic parameters in perimetry and OCT. In particular, the mean and inferior retinal nerve fibre layer thickness, the rim area, and the vertical CD ratio revealed to be significant parameters in glaucomatous eyes.

Measurement properties of the Western Ontario Shoulder Instability index in Dutch patients with shoulder instability.

BACKGROUND: The Western Ontario Shoulder Instability index (WOSI) is a patient-reported outcome measure for patients with shoulder instability. The purpose of this study was to validate the WOSI in a Dutch population by evaluating its structural validity, internal consistency, measurement error, reliability, and construct validity. Floor and ceiling effects were also addressed. METHODS: Two cohorts were recruited, including a total of 138 patients with shoulder instability. Confirmatory factor analysis was used to assess the structural validity and Cronbach's α to assess internal consistency. The measurement error was calculated as the smallest detectable change (SDC). Reliability (test-retest) was estimated in a subgroup of 99 patients who completed the re-test after a mean of 13 days (5-30 days). Reliability was calculated with the intraclass correlation coefficient (ICC). Construct validity was evaluated by comparing the WOSI with the Oxford Shoulder Instability Score (OSIS), the Simple Shoulder Test, the Oxford Shoulder Score, the Disability of the Arm, Shoulder, and Hand assessment (DASH), and the Short Form-36 Health Survey. Measurement properties were evaluated for both the total WOSI score and its four domains. RESULTS: Factor analysis did not confirm the validity of the four domains. Best results were found for a one-factor model. Internal consistency was good, with Cronbach's α ranging from 0.93 to 0.96. Reliability was excellent (ICC 0.88-0.92 for all subscales). The measurement error (SDC) was 23.0% for the total WOSI and 23% to 28% for the subscales (on a scale of 0-100). Regarding the construct validity, 76% of the results were in accordance with the hypotheses, including a high correlation with the OSIS (0.82) and DASH (0.81) assessments. No floor or ceiling effects were found. CONCLUSION: The Dutch version of WOSI showed good reliability and validity in a cohort of patients with shoulder instability, although the factor structure remains unclear.

[Surgical treatment of chronic macular oedema with a combination therapy]. / Operative Behandlung des chronischen Makulaödems durch eine Kombinationstherapie.

BACKGROUND: The treatment of therapy-resistent chronic macular oedema remains a challenge. Therefore a combination therapy, consisting of medical, biological and mechanical components was assessed. METHODS: A surgical treatment was performed in 35 eyes (34 patients) with chronic and therapy-resistant macular oedema, resulting from diabetic maculopathy (n = 25), vitreoretinal traction (n = 7) or following a retinal venous occlusion (n = 3). An intravitreal injection of bevacizumab was given on the day before surgery, consisting of pars plana vitrectomy with ILM peeling with Brilliant Blue G (BBG), as well as an air tamponade combined with postoperative prone positioning. The visual function and the central retinal thickness were measured in follow-up. RESULTS: Functionally, the visual acuity could be stabilised to an average of 0.18 and macular oedema was reduced in most patients. Anatomically, a significant reduction in central macular thickness by 193 µm (29 %), from 598 µm to 405 µm (p < 0.001), and a regression in the intraretinal cystoid changes were observed. No significant complications occurred, whereas in 6 patients additional consecutive treatment was necessary. CONCLUSION: A stabilisation of the visual acuity and an improvement in the structural retinal situation could be achieved by an elaborate combination therapy, based on a pharmacological, a biological and a mechanical approach. Long-term follow-up and consecutive supplementary treatments are necessary to ensure the functional stability.

How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. DESIGN: Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio. SETTING: Primary care, recruitment from February 2020 to August 2022. PARTICIPANTS: 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)). INTERVENTIONS: Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution). MAIN OUTCOME MEASURES: Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability. RESULTS: Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability. CONCLUSIONS: Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis. TRIAL REGISTRATION NUMBER: WHO ICTRP NL8193.

Natural course of cutaneous warts among primary schoolchildren: a prospective cohort study.

PURPOSE: Because cutaneous warts resolve spontaneously and available treatments often fail, family physicians and patients may consider a wait-and-see policy. We examined the natural course of cutaneous warts and treatment decisions in a prospective observational cohort of primary schoolchildren. METHODS: We inspected the hands and feet of children aged 4 to 12 years from 3 Dutch primary schools for the presence of warts at baseline and after a mean follow-up of 15 months. Parental questionnaires at follow-up provided information on inconvenience caused by warts and any treatments used. RESULTS: Of the 1,134 eligible children, 1,099 (97%) participated, of whom 366 (33%) had cutaneous warts at baseline. Among these children with warts, loss to follow-up was 9% and the response rate to the parental questionnaires was 83%. The complete resolution rate was 52 per 100 person-years at risk (95% CI, 44-60). Younger age (hazard ratio = 1.1 per year decrease; 95% CI, 1.0-1.2) and non-Caucasian skin type (hazard ratio = 2.0; 95% CI, 1.3-2.9) increased the likelihood of resolution. During follow-up, 38% of children with warts at baseline treated their warts: 18% used over-the-counter treatment only, 15% used a family physician-provided treatment only, and 5% used both. Children were more likely to initiate treatment if the warts measured at least 1 cm in diameter (odds ratio = 3.2; 95% CI, 1.9-5.3) and especially if parents reported that the warts caused inconvenience (odds ratio = 38; 95% CI, 16-90). CONCLUSIONS: One-half of primary schoolchildren with warts will be free of warts within 1 year. Young age and non-Caucasian skin type enhance resolution. Children with large or inconvenient warts are more likely to start treatment. These findings will be useful in the process of shared decision making with parents and children.

Molluscum contagiosum survey - common approach and attitude towards treatment and research in Dutch general practice.

BACKGROUND: Molluscum contagiosum (MC) can cause significant burden in children. So far, pharmacological treatment has not been proven beneficial. More rigorous interventions have not been well studied. Current guidelines advise a "wait and see" policy. However, children and their parents frequently visit their GP requesting intervention. Therefore, the aim of this study was to gain insight into the approach to MC by GPs and parents' expectations and to investigate willingness to participate in an interventional study. METHODS: A survey study was carried out among GPs and parents using a questionnaire for each group inquiring about MC and potential study participation. Descriptive statistics were used to analyze results and logistical regression to investigate factors influencing participation. RESULTS: The majority of GPs (88%) preferred an expectative approach; only 21% were willing to participate in a trial as proposed. GPs estimating ≥ 50% of parents would request treatment, were more likely to participate. Most responding parents did or would visit their GP requesting treatment. In contrast to GPs, 58% were willing to participate. Parents preferring cryotherapy or curettage were more likely to participate. CONCLUSION: Our study demonstrated that the majority of GPs preferred a conservative approach, adhering to current guidelines. However, most parents preferred treatment to resolve MC and symptoms. Parents' willingness to participate was much higher than GP's, reflecting parents' desire for treatment. These findings underscore the need for continued therapeutic research. Careful preparation and selection of GPs and patients will be essential to ensure the feasibility of such an endeavor. TRIAL REGISTRATION: This survey study was not part of a clinical trial.

High variability in what is considered important to report following instability surgery: a Delphi study among Dutch shoulder specialists.

Background: Standardized reporting leads to high-quality data and can reduce administration time. The aim of this study was to (1) get an insight into the variability of what is considered important to report in the surgical report following shoulder instability surgery and (2) determine which elements should be included in the surgical report following shoulder instability surgery according to Dutch surgeons using a Delphi method. Methods: Dutch orthopedic shoulder surgeons were included in a panel for a Delphi study consisting of 3 rounds. Importance of the elements was rated on a 9-point Likert scale. High variability was defined as an element that received at least 1 score between 1 and 3 and 1 score between 7 and 9 in round 3. Consensus was defined as ≥80% of the panel giving a score of 7 or more. Results: Seventeen shoulder specialists completed all 3 rounds and identified a total of 82 elements for the arthroscopic Bankart repair and 60 for the open Latarjet. High variability was observed in 57 (70%) and 52 (87%) of the elements, respectively. After round 3, the panel reached consensus on 27 and 11 elements that should be mentioned in the surgical report following arthroscopic Bankart repair and open Latarjet. Conclusion: There is high variability in what shoulder specialists regard essential to report. Consensus was reached on 27 and 11 elements to be reported following arthroscopic Bankart repair and open Latarjet, respectively. Future studies on an international scale can further improve data collection and communication between specialists.

Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening condition associated with increased vascular permeability. The vascular endothelial growth factor (VEGF) system and its receptors have been identified as the main angiogenic factors responsible for increased capillary permeability and are therefore discussed as crucial for the occurrence of OHSS. Recently, a number of soluble receptors for the VEGFs have been detected (sVEGF-Rs) and it has been shown that these sVEGF-Rs compete with the membrane-standing VEGF-R to bind VEGFs. METHODS: We analyzed the serum levels of soluble VEGF-R1, -R2 and -R3 in 34 patients suffering from OHSS and in 34 controls without this disease. In a subgroup analysis, we correlated the severity of the OHSS with the detected amounts of VEGF-R1, -R2 and -R3. In addition, we determined the amount of total VEGF-A in the samples. RESULTS: All the three soluble VEGF receptors tended to be higher in the control group compared with that in the OHSS group but this difference only reached significance for sVEGF-R2 (mean ± SEM: 15.5 ± 0.6 versus 13.8 ± 0.5 ng/ml, respectively, P< 0.05). In the subgroup analysis, sVEGF-R2 levels decreased as the severity of OHSS increased (OHSS-I: 16.8 ± 1.9 ng/ml and OHSS-III: 12.7 ± 1.0 ng/ml, P< 0.05) Moreover, the serum levels of total VEGF-A were higher in the OHSS group than those in the controls (537.7 ± 38.9 versus 351 ± 53.4 pg/ml, respectively P< 0.05). CONCLUSIONS: We propose that VEGF-A plays a role in the occurrence of OHSS, that the amount of biologically available VEGF-A is modulated by sVEGF-Rs and that different combinations of VEGF-A and sVEGF-R levels might contribute to the severity of OHSS.

Proximity to death is associated with frequency of GP contacts in the oldest old: the Leiden 85-plus study.

BACKGROUND: the relationship between proximity to death and the amount of care provided by general practitioners (GPs) is largely unknown. OBJECTIVE: to examine the influence of the proximity to death on the frequency and length of GP contacts in the oldest old. STUDY DESIGN: this population-based follow-up study included 599 inhabitants of Leiden, the Netherlands. At ages 85-90 years, the frequency and length of GP contacts during the previous year were collected. METHODS: the influence of age and proximity to death on contact frequency and time was analysed with linear mixed modelling. RESULTS: in a model including 'age' alone, mean contact frequency during surviving years increased with 0.25 contacts/year [95% confidence interval (CI) 0.04-0.45, P = 0.019] and mean contact time with 11.04 min/year (95% CI: 5.42-16.67, P < 0.001). In a model including 'age' and 'proximity to death', those who died compared with those who survived had 11.94 contacts (95% CI: 10.86-13.01) more that year and 323 min (95% CI: 294-353, P < 0.001) more time, with no effect of 'age'. CONCLUSIONS: the observed increase in utilisation of GP care of the oldest old depends more on the proximity to death and less on age alone. Being old only results in a small increase in the GP's workload.

Interventions for ingrowing toenails.

BACKGROUND: Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non-surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first-choice treatment. OBJECTIVES: To evaluate the effects of non-surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. SEARCH METHODS: We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of non-surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow-up period of at least one month. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non-surgical interventions, and 19 were on surgical interventions.The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies.None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications - infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes.Surgical interventions were better at preventing recurrence than non-surgical interventions with gutter treatment (or gutter removal), and they were probably better than non-surgical treatments with orthonyxia (brace treatment).In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation.In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69).None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone-iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. AUTHORS' CONCLUSIONS: Surgical interventions are more effective than non-surgical interventions in preventing the recurrence of an ingrowing toenail.In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes.Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time.

Evaluation of a novel multiplex human papillomavirus (HPV) genotyping assay for HPV types in skin warts.

Human papillomaviruses (HPV) of the genera alpha, mu, and nu induce benign tumors of the cutaneous epithelia that constitute a significant burden for immunocompromised adults. Currently, no gold standard for genotyping of these HPV types exists. In this study, we describe the prevalence of genus alpha, mu, and nu HPV types in cutaneous warts. We developed a novel multiplex HPV genotyping assay, BSwart-PCR/MPG (BSwart), to type sensitively and specifically 19 cutaneous HPV types frequently found in warts. BSwart-PCR/MPG is based on a multiplex PCR using broad-spectrum primers and subsequent multiplex hybridization to type-specific probes coupled to Luminex beads. In a first application comprising 100 cutaneous warts, the assay was compared to another, recently described genotyping assay, the HSL-PCR/MPG. When a 10-fold dilution series was used, the detection limit was between 10 and 100 HPV genomes per PCR. When comparing the two assays, there was an excellent agreement in detecting dominant HPV types; however, we also obtained evidence for a higher sensitivity of the BSwart assay for multiple infections in these cutaneous warts. Using BSwart, HPV was found in 95% of wart preparations, with HPV1 being most prevalent, followed by types 27, 57, and 2. Both novel BSwart and HSL-PCR/MPG HPV genotyping assays are powerful high-throughput tools that could be used to learn more about the natural history of cutaneous HPV. They would be advantageous to monitor the efficacy of future skin HPV vaccines and to identify novel HPV vaccine candidates.

Design of the Verbiest trial: cost-effectiveness of surgery versus prolonged conservative treatment in patients with lumbar stenosis.

BACKGROUND: Degenerative changes of lumbar spine anatomy resulting in the encroachment of neural structures are often regarded progressive, ultimately necessitating decompressive surgery. However the natural course is not necessarily progressive and the efficacy of a variety of nonsurgical interventions has also been described. At present there is insufficient data to compare surgical and nonsurgical interventions in terms of their relative benefit and safety. Previous attempts failed to provide clear clinical recommendations or to distinguish subgroups that substantially benefit from a certain treatment strategy. We present the design of a randomized controlled trial on (cost-) effectiveness of surgical decompression versus prolonged conservative treatment in patients with neurogenic intermittent claudication caused by lumbar stenosis. METHODS/DESIGN: The aim of the Verbiest trial is to evaluate the effectiveness of prolonged conservative treatment compared to decompressive surgery. The study is a multi-center randomized controlled trial with two parallel groups design. Patients (age over 50) presenting to the neurologist or neurosurgeon with at least 3 months complaints of neurogenic intermittent claudication and considering surgical treatment are eligible for inclusion. Participants are randomly allocated to either prolonged conservative treatment, receiving further treatment from their general practitioner and physical therapist, or allocated to surgery and operated within 4 weeks. Primary outcome measure is the functional assessment of the patient as measured by the Zurich Claudication Questionnaire at 24 months of follow-up. Data is analyzed according to the intention to treat principle. DISCUSSION: With a cost-effectiveness analysis the trade off between the costs of prolonged conservative treatment and delayed surgery in a smaller number of patients are compared with the current policy of surgical management. As surgery is expected to be inevitable in certain subgroups of patients, the distinction of and classification by predictive patient characteristics is most relevant to clinical practice. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2216.