Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe.

Lightening skin tone is an ancient and well-documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side-effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side-effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health problems due to the presence of illegal products on the market is summarized.

Does cancer risk increase with HbA1c, independent of diabetes?

BACKGROUND: The risks for several cancer types are increased in people with diabetes. Hyperglycaemia, hyperinsulinaemia, inflammation and altered hormonal concentrations are common characteristics between the two diseases and can all be linked to hyperglycaemia. METHODS: Here, we use glycated haemoglobin (HbA1c) as a biomarker for chronic hyperglycaemia. We explore whether cancer risk increases with HbA1c, independent of diabetes, and, therefore, if risk is already increased below the diabetic HbA1c range, by analysing data from current studies linking HbA1c to risk of several cancer types. RESULTS: The data reveal that chronic hyperglycaemia correlates with increased cancer risk for a number of cancers, except prostate cancer. Evidence is also provided that risk is already increased in the pre-diabetic and normal ranges for several cancers. CONCLUSIONS: These results merit urgent investigation into the risks and advantages of updating recommendations for stricter glycaemic control in diabetic and non-diabetic subjects, as this could help reduce the risk of cancer incidence and mortality.

Molecular surveillance of multi- and extensively drug-resistant tuberculosis transmission in the European Union from 2003 to 2011.

The European Centre for Disease Prevention and Control (ECDC) initiated a project on the molecular surveillance of multi- and extensively drug-resistant tuberculosis (MDR-/XDR-TB) transmission in the European Union (EU) in the period from 2009 to 2011. In total, 2,092 variable number of tandem repeat (VNTR) patterns of MDR-/XDR-TB Mycobacterium tuberculosis isolates were collected, originating from 24 different countries in the period 2003 to 2011. Of the collected VNTR patterns, 45% (n=941) could be assigned to one of the 79 European multiple-country molecular fingerprint clusters and 50% of those (n=470) belonged to one extremely large cluster caused by Beijing strains of one genotype. We conclude that international transmission of MDR-/XDR-TB plays an important role in the EU, especially in the eastern part, and is significantly related to the spread of one strain or clone of the Beijing genotype. Implementation of international cluster investigation in EU countries should reveal underlying factors of transmission, and show how TB control can be improved regarding case finding, contact tracing, infection control and treatment in order to prevent further spread of MDR-/XDR-TB in the EU.

A strategy for the identification of plants in illegal pharmaceutical preparations and food supplements using chromatographic fingerprints.

The detection of regulated and forbidden herbs in pharmaceutical preparations and nutritional supplements is a growing problem for laboratories charged with the analysis of illegal pharmaceutical preparations and counterfeit medicines. This article presents a feasibility study of the use of chromatographic fingerprints for the detection of plants in pharmaceutical preparations. Fingerprints were developed for three non-regulated common herbal products--Rhamnus purshiana, Passiflora incarnata L. and Crataegus monogyna--and this was done by combining three different types of detection: diode-array detection, evaporative light scattering detection and mass spectrometry. It is shown that these plants could be detected in respective triturations of the dry extracts with lactose and three different herbal matrices as well as in commercial preparations purchased on the open market.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width.

OBJECTIVES: To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN: Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS: Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION: High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Developing a theory of family care during critical illness.

Background: The critical illness of a loved one can negatively affect all family members (FMs), leading to the interruption of family functioning and integrity. Hospitalisation is a stressful, unplanned event for both the patient and FMs and is associated with psychological disturbances, emotional distress and altered family roles and functioning. Objectives: To develop a theory of family care in critical care units (CCUs) for the South African setting. Methods: Grounded theory, based on Strauss and Corbin's school of thought, was used. Audio-recorded in-depth interviews were conducted with 32 participants (9 FMs, 17 critical care nurses and 6 doctors) at a private hospital (3 CCUs) and a state hospital (10 CCUs). Data analysis involved open, axial and selective coding. Results: The theory of family care during critical illness was identified. The core concept of the theory is empowerment, informed by the underlying constructs of information sharing, proximity, garnering resources, and cultural and religious cooperation. Conclusion: The concepts of this theory can equip healthcare professionals in CCUs to provide appropriate family care for meeting the needs of patients' FMs and, in so doing, contribute to families having a more manageable critical care experience during the illness of their loved one. Contributions of the study: This study adds to the limited body of knowledge regarding family care within the South African context. The study provides a theory to promote therapeutic partnerships between health care professionals, patients and FMs that will provide support for both the patient and FMs.It is further anticipated that the findings of the study will contribute not only to nurses' critical care curriculum, which currently includes very limited family support content, but also be helpful to doctors working in intensive care units.

Economic and public health impact of decentralized HIV viral load testing: A modelling study in Kenya.

Kenya has the world's 4th largest HIV burden. Various strategies to control the epidemic have been implemented, including the implementation of viral load (VL) testing to monitor HIV patients on ARVs. Like many resource limited settings, Kenya's healthcare system faces serious challenges in effectively providing quality health services to its population. Increased investments to strengthen the country's capacity to diagnose, monitor and treat diseases, particularly HIV and TB, continue to be made but are still inadequate in the face of global health goals like the UNAIDS 90:90:90 which require scaling up of VL tests amid existing constraints. In Kenya, there is an increase in the demand for VL tests amidst these existing constraints. The GeneXpert system is a diagnostic point-of-care technology that can quantify, amongst others, HIV VL. Currently, GeneXpert technology is widely distributed in Kenya for testing of tuberculosis. This study aimed to determine the economic and public health impact of incorporating VL test modules on the existing GeneXpert infrastructure. Markov models were constructed for different populations (non-pregnant adults, pregnant women and children). The scenarios analysed were 100% centralized VL testing compared to 50% GeneXpert plus 50% centralized VL testing, with time horizons of 5 years for the adult and child populations, and 31 months for the pregnant population. Incremental effectiveness was measured in terms of the number of HIV transmissions or opportunistic infections avoided when implementing the GeneXpert scenario compared to a 100% centralized scenario. The model indicated that, for all three populations combined, the GeneXpert scenario resulted in 117 less HIV transmissions and 393 less opportunistic infections. The cost decreased by $21,978,755 for the non-pregnant and pregnant adults and $22,808,533 for non-pregnant adults, pregnant adults and children. The model showed that GeneXpert would cost less and be more effective in terms of total cost per HIV transmission avoided and the total cost per opportunistic infection avoided, except for the pregnant population, when considered separately.

Culdocele repair in female pelvic organ prolapse.

OBJECTIVES: To review patients with a culdocele, a wide and deep cul-de-sac, and to report the results of treatment by sacrocolpopexy. METHODS: A retrospective review of 117 patients with a culdocele identified by clinical examination and intraoperatively. RESULTS: The mean age and parity of the patients were 61.4 years and 3.1, respectively. Bladder complaints occurred in 46% of patients and bowel problems in 74% (mainly obstructed defecation). Something protruded through the vaginal introitus in 84% of patients. All patients were treated with a sacrocolpopexy: 96% with mobilization and elevation of the rectum (rectopexy), and 79% with Burch colposuspension. Follow-up results were obtained for 98% of the patients (mean, 14.7 months). Recurrent prolapse occurred in 10% of patients. CONCLUSIONS: A culdocele differs from an enterocele because it a distended and deep cul-de-sac without a true hernia between the distal vagina and rectum. Sacrocolpopexy resulted in a 10% recurrence rate of prolapse.

Isolation of Mycobacterium mageritense from the lung of a harbor porpoise (Phocoena phocoena) with severe granulomatous lesions.

Post-mortem investigation of a harbor porpoise (Phocoena phocoena) found dead on the beach of the island of Vlieland, The Netherlands, revealed severe granulomatous changes in the right lung lobe. Ziehl Neelsen staining demonstrated relatively large acid-fast rods. Mycobacterial culture yielded a fast-growing mycobacterium, which was identified by molecular biological methods as Mycobacterium mageritense. Autolysis prevented histopathology. It was tentatively concluded that the granulomatous changes were the cause of porpoise's death and that M. mageritense was the causative agent. This is the first report of the isolation and molecular identification of this mycobacterium in a nonhuman animal species and the first association with the marine environment.

[Sensible family planning: do not have children too late, but not too early either]. / Verstandige gezinsplanning: niet te laat, maar ook niet te vroeg kinderen krijgen.

Due to family planning, Dutch women are increasingly having their first child between 25 and 35 years of age. Compared to 13 other EU countries, Dutch women are having fewer children both earlier and later on in life. From 1970 onwards in the Netherlands, the mean age at first childbirth has increased by 5 years to 29.4 years. The main cause for the rising age at first childbirth is the decrease in the number of young mothers. In 2006, 7% of all childbearing women had their first child after the age of 36; this is just 4.7% higher than in 1970. The percentage of women remaining childless by delaying childbearing too long increased by 0.9%. Considering the social and medical problems in later life, it would not be wise to encourage women to have their babies at a young age, certainly not before the age of 23. Women planning a family should take into account the decline in natural fertility after the age of 35; the future mothers of the Netherlands seem to be planning and deciding wisely.

[Guideline 'Diagnosis and treatment of obesity in adults and children']. / Richtlijn 'diagnostiek en behandeling van obesitas bij volwassenen en kinderen'.

The multidisciplinary guideline 'Diagnosis and treatment of obesity in adults and children' developed by the Dutch Institute for Healthcare Improvement (CBO) is based on published scientific evidence whenever possible. Diagnosis ofobesity requires a body-mass index (BMI) of 30 kg/m2 or more with additional assessment of waist circumference and comorbidity. For children and adolescents, use ofage-specific BMI thresholds is recommended. Treatment of obesity consists of multiple lifestyle interventions for at least 1 year, followed by long-term management aimed at weight maintenance or any further weight loss. In adults, the goal is to achieve weight loss of at least 5% and a reduction in waist circumference of at least 10% after 1 year. If weight loss after 1 year is less than 5%, the addition of pharmacological interventions to lifestyle interventions can be considered. Bariatric surgery can be considered for patients with a BMI of 40 kg/m2 or more and for those with BMI 35-40 kg/m2 with one or more comorbidities. Pharmacological and surgical interventions are not recommended for children and adolescents.

Metal ion levels after metal-on-metal Ring total hip replacement: a 30-year follow-up study.

Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings. We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs.

Computational fluid dynamics modeling of insertion and advancement of a reamer into the intramedullary canal of a long bone.

The effect of reaming velocity on the pressure distribution within the bone was investigated numerically by solving the full three-dimensional momentum equations together with the continuity equation using the finite element technique. Viscosity was also varied to obtain a pressure envelope. It was found that all the experimental data follow the same trends as the envelopes predicted by the finite element model. It was clear that an increase in either the implant insertion rate or the viscosity resulted in an increase in pressure in the intramedullary canal.

Prospects of labour migration pressure in Algeria, Morocco, Tunisia and Turkey.

Gaining control over refugee flows and undocumented migrants currently dominate the media and political arenas in Europe. Underlying driving and enduring forces, such as employment-related migration pressure, tend to be relegated to the background. In this article, we explore migration pressure prospects up to 2035 in four countries with a tradition of emigration to Europe: Algeria, Morocco, Tunisia and Turkey. More specifically, we first derive a simple decomposition model based on the relationship between working-age population (WAP) growth and growth of gross domestic production (GDP) and worker productivity (GDP/W). From this model, we derive an indicator of migration pressure: size of the non-employed population in a country. This model is then used as framework for deriving storylines for three different scenarios of economic and demographic change up to 2035. Subsequently, storylines are operationalized, leading to scenario estimates of migration pressure up to 2035. The implications of the results are then discussed. Time series of macro-level economic and demographic data are used to underpin scenario assumptions. Scenario results suggest that in all countries employment ratios are expected to increase, but only in Tunisia is the size of the non-employed population-our indicator of migration pressure-expected to decline, irrespective of the scenario. Depending on the scenario, migration pressure remains high in Turkey and Morocco and may even become somewhat higher. The general conclusion is that in the long term, after 2035, labour migration pressure can be expected to decrease because the growth and size of the working-age population is decreasing while employment ratios are rising.

Chromatographic impurity fingerprinting of genuine and counterfeit Cialis® as a means to compare the discriminating ability of PDA and MS detection.

Public health is threatened worldwide by counterfeit medicines. Their quality, safety and efficacy cannot be guaranteed since no quality control is performed during and/or after the manufacturing process. Characterization of these products is a very important topic. During this study a High Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) and a High Performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) method were developed to analyse both genuine and counterfeit samples of Cialis®. The obtained PDA and MS fingerprints were explored and modelled using unsupervised Principal Component Analysis (PCA) and supervised Partial Least Squares and its discriminant variant (PLS, PLS-DA) as well the classification methods including Soft Independent Modelling of Class Analogy (SIMCA) and the k Nearest Neighbour classifier (kNN). Both MS1 and MS2 data and data measured at 254 nm and 270 nm were used with the aim to test the potential complementarity of PDA and MS detection. First, it was checked if both groups of fingerprints can support differentiation between genuine and counterfeit medicines. Then, it was verified if the obtained multivariate models could be improved by combining information present in MS and PDA fingerprints. Survey of the models obtained for the 254 nm data, 270 nm data and 254_270 nm data combination showed that a tendency of discrimination could be observed with PLS. For the 270 nm data and 254_270 nm data combination a perfect discrimination between genuine and counterfeit medicines is obtained with PLS-DA and SIMCA. This shows that 270 nm alone performs equally well compared to 254_270 nm. For the MS1 and MS1_MS2 data perfect models were obtained using PLS-DA and kNN, indicating that the MS2 data do not provide any extra useful information to acquire the aimed distinction. When combining MS1 and 270 nm perfect models were gained by PLS-DA and SIMCA, which is very similar to the results obtained for PDA alone. These results show that both detectors have a potential to reveal chemical differences between genuine and counterfeit medicines and thus enable the construction of diagnostic models with excellent recognition. However, if a larger sample set, including more possible sources of variation, is analysed more sophisticated techniques such as MS might be necessary.

Infection in hip arthroplasty after previous injection of steroid.

Immunosuppression following intra-articular injections of steroid into the hip may interfere with asepsis in a subsequent total hip arthroplasty (THA). We have undertaken a retrospective, matched, cohort study of infective complications after THA, in 40 patients who had received such an injection and 40 who had not. In the injection group there were five revisions, four of which were for deep infection. There were none in the matched group. The overall rate of revision in our database of 979 primary THAs was 1.02%. Six additional patients who had received injections underwent investigation for infection because of persistent problems in the hip as compared with one in the control group.

The effect of the summer 2003 heat wave on mortality in the Netherlands.

In the Netherlands, between 1400 and 2200 deaths in the summer of 2003 may have been heat-related. The fact that the maximum temperatures were lower than in some other European countries, and occurred in less heavily populated areas, may have led to mortality figures that were relatively less dramatic. The temporarily increased death rates are only partly due to a forward shift of mortality. Heat-related mortality was most pronounced among the elderly in nursing homes.

Development of a Stationary Phase Optimised Selectivity Liquid Chromatography based screening method for adulterations of food supplements for the treatment of pain.

Illegally adulterated dietary supplements are an increasing problem worldwide. One of the important groups of often adulterated products are the dietary supplements, sold for the treatment of pain. These often contain analgesics, a heterogeneous group of molecules, containing both hydrophilic and hydrophobic compounds. The development of a screening method for these components, especially when mass spectrometric detection is not available, necessitates chromatographic separation, difficult to achieve with traditional chromatographic columns. In this paper Stationary Phase Optimised Selectivity Liquid Chromatography was used for the development of a screening method for nine analgesics, codeine and caffeine, often present in this type of dietary supplements. The method shows a good separation of all the compounds, allowing the screening to be performed with diode array detection and is fully compatible with mass spectrometry. The method was validated for its selectivity following the guidelines as described for the screening of pesticide residues and residues of veterinary medicines in food.

Mycobacterium tuberculosis genotypic drug resistance patterns and clustering in Jayapura, Papua, Indonesia.

BACKGROUND: Little is known about drug-resistant tuberculosis (TB) and its transmission in Papua, which has one of the highest rates of TB in Indonesia. DESIGN: We examined genotypic drug resistance patterns using multiplex ligation-dependent probe amplification and the degree of molecular clustering using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) among 199 consecutive pulmonary TB patients in Jayapura, Papua. RESULTS: Drug resistance mutations were present in 30/198 (15.2%) patients: 16/144 (11.1%) primary cases and 14/51 (27.5%) retreatment cases. Genotypic resistance to rifampicin was found in 15 (7.6%) patients, to isoniazid in 19 (9.6%), to ethambutol in 7 (3.5%), and to streptomycin and second-line injectable drugs in 5 (2.5%) patients. Eight (4.0%) patients had multidrug-resistant TB, while no mutations were found for fluoroquinolones. The most common lineage found among all isolates was East-African Indian (n = 66, 33.7%), followed by Euro-American (n = 38, 19.4%). Drug resistance mutations were more common among Beijing strains than other lineages. Of the 30 drug-resistant isolates, 12 (40.0%) fell into four clusters that were separate from drug-susceptible clusters as determined using MIRU-VNTR. CONCLUSIONS: These are the first genotypic drug resistance data from Jayapura, Papua, showing moderate rates of resistance to first-line drugs and likely transmission of drug-resistant TB.