Swedish Patient Research Articles

Patients With Celiac Disease Have an Increased Risk for Pancreatitis

Patients with celiac disease have been reported to be at increased risk for pancreatitis and pancreatic insufficiency, but the risk might have been overestimated because of patient selection and limited numbers of patients for analysis. Furthermore, no distinction has been made between patients with gallstone-related and non-gallstone-related pancreatitis. We performed a nationwide study to determine the risk for any pancreatitis or subtype of pancreatitis among patients with biopsy-verified celiac disease. We analyzed data from patients in Sweden with celiac disease (n = 28,908) who were identified on the basis of small intestinal biopsy records from 28 pathology departments (those with villous atrophy, Marsh 3). Biopsies were performed from 1969 to 2008, and biopsy report data were collected from 2006 to 2008. Patients with pancreatitis were identified on the basis of diagnostic codes in the Swedish Patient Register and records of pancreatic enzyme use in the Swedish Prescribed Drug Register. Data were matched with those from 143,746 individuals in the general population; Cox regression was used to estimate hazard ratios (HRs) for pancreatitis. We identified 406 patients with celiac disease who were later diagnosed with pancreatitis (and 143 with expected pancreatitis) (HR, 2.85; 95% confidence interval [CI], 2.53-3.21). The absolute risk of any pancreatitis among patients with celiac disease was 126/100,000 person-years, with an excess risk of 81/100,000 person-years. The HR for gallstone-related acute pancreatitis was 1.59 (95% CI, 1.06-2.40), for non-gallstone-related acute pancreatitis HR was 1.86 (95% CI, 1.52-2.26), for chronic pancreatitis HR was 3.33 (95% CI, 2.33-4.76), and for supplementation with pancreatic enzymes HR was 5.34 (95% CI, 2.99-9.53). The risk of any pancreatitis within 5 years of diagnosis was 2.76 (95% CI, 2.36-3.22). Based on an analysis of medical records from Sweden, patients with celiac disease have an almost 3-fold increase in risk of developing pancreatitis, compared with the general population.

Men's Perceived Experiences of Abuse in Health Care: Their Relationship to Childhood Abuse

It has previously been shown in a Swedish female patient sample, that there is a statistical correlation between experiences of childhood emotional, physical and/or sexual abuse (EPSA), and perceived abuse in health care (AHC). Our aim was to investigate whether similar correlations exist in a Swedish male sample. The study was based on the male version of NorVold Abuse Questionnaire (m-NorAQ), and performed in a random sample from the Swedish population (n = 2,924), and a patient sample (n = 1,767). Any lifetime EPSA was associated to any lifetime AHC, and victims of adult AHC reported childhood EPSA more often than non-victims. There seems to be a dose-response relationship between childhood EPSA and adult AHC in both female and male samples, i.e. childhood experiences of EPSA is a risk factor for experiencing AHC in adulthood.

Resource Utilization and Cost of Heart Failure associated with Reduced Ejection Fraction in Swedish Patients

Aim:The purpose of this study was to assess healthcare utilization and costs for heart failure patients with reduced ejection fraction (HF-REF) in Sweden.Methods and Results:This was a retrospective, population-based cohort study of patients diagnosed with HF-REF during a period of 18 months at 31 primary care centers in Uppsala County, Sweden. Data was obtained from computerized records from these centers, the Swedish Patient Registry, the Swedish Prescription Registry, the Cause of Death Registry, and a local echocardiography registry maintained by the Department of Physiology, Uppsala University Hospital. Main outcome measures were cardiovascular and heart-failure-related hospitalizations, outpatient visits, medication utilization, mortality (all-cause, cardiovascular, and heart-failure), and healthcare costs for HF-REF patients. During the index period, 252 heart failure patients had a left ventricular ejection fraction measurement ≤40% and were categorized as having HF-REF. More than half of the patients had ≥1 cardiovascular or heart failure-related hospitalization. On average, patients had >2 such hospitalizations annually. They also averaged ∼1 cardiovascular or heart-failure-related outpatient visit per year. All-cause mortality was high: 15.9% patients died within 1 year after the index date. The mean annual cost per patient for heart-failure-related hospitalizations was SEK 72,613 (EUR 7610). In contrast, annual prescription costs were low, on average 3% of total cost (SEK 3503, EUR 367 per patient)Limitations:The main limitations of this study include a short follow-up time and small sample size. Also, certain data were missing, such as echocardiograms (available for only 28% of patients), and information on patients’ New York Heart Association (NYHA) functional class, validity period for prescriptions or the units of medication prescribed, and medication dosing. Furthermore, the overall mortality could have been under-estimated, as only the primary cause of death was included in the analysis.Conclusions:The main burden associated with HF-REF is related to hospitalizations for heart-failure events. Effective treatment options that decrease hospitalization rates could reduce patients’ suffering and potentially offer considerable cost savings.

Abstract 3656: Cathepsin E, Maspin, PLK1, and Survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer

Abstract The majority of patients with bladder cancer are initially diagnosed with noninvasive or superficially invasive urothelial tumors. These tumors form a heterogeneous group, spanning from benign low grade Ta tumors that rarely progress to high grade T1 tumors with concomitant CIS that progress in up to 60% of cases. The histopathological parameters used in the clinic cannot precisely predict the individual disease course, and no molecular markers are currently in clinical use for predicting tumor recurrence or later progression. Previously, we have identified gene expression signatures for prediction of disease outcome for patients with non-muscle invasive bladder cancer. The aim of the present study was to validate key candidate markers from these signatures at the protein level. Four proteins were selected for investigation: Cathepsin E, Maspin, PLK1, and Survivin. We used three different tissue-microarrays with a total of 693 non-muscle invasive urothelial carcinomas from Danish, Swedish, and Spanish patient cohorts. The Danish patient cohort was used for optimizing IHC cutoff values and the Swedish-Spanish cohort was used as independent validation. Protein expression was measured by IHC and antibody specificity was validated by Western blotting. In the Danish patient cohort, we found the expression of Cathepsin E, Maspin, PLK1, and Survivin to be significantly associated with progression to stage T2-4 bladder cancer (for each marker: log-rank test; p<0.001). Multivariate Cox regression analysis identified Cathepsin E (p<0.001), Maspin (p=0.001), PLK1 (p=0.021), and Survivin (p=0.001) as independent prognostic markers. Furthermore, Cathepsin E, Maspin and Survivin expression significantly sub-grouped patients already stratified by EORTC risk scores. Survivin expression (log-rank test; p=0.004) and Maspin expression (log-rank test; p<0.001) significantly subgrouped the EORTC low risk patients. Cathepsin E expression subgrouped the EORTC high risk patients (log-rank test; p=0.001). Finally, we successfully validated the results in tumors from 410 patients from Sweden and Spain. Using univariate Cox regression analysis we identified Cathepsin E (p=0.002), Maspin (p<0.001), PLK1 (p=0.003), and Survivin (p=0.002) to show significant association with disease progression to muscle invasive bladder cancer in the Spanish-Swedish validation cohort. Furthermore, in multivariate analysis Cathepsin E (p=0.019) and Survivin (p=0.014) were significantly associated with disease progression when adjusting for other known clinical and histopathological risk factors. We conclude that all four protein markers may have prognostic value in non-muscle invasive bladder cancer for guiding optimal treatment of patients. Additional prospective studies are needed for further validation of the clinical relevance of the marker panel. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3656. doi:1538-7445.AM2012-3656

Cathepsin E, Maspin, Plk1, and Survivin Are Promising Prognostic Protein Markers for Progression in Non-Muscle Invasive Bladder Cancer

Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. In this study, we investigated the prognostic value of the protein expression of cathepsin E, maspin, polo-like kinase 1 (Plk1), and survivin in patients with stage Ta and T1 urothelial carcinomas. Transcripts from the four genes encoding these proteins were previously included in gene expression signatures for outcome prediction for Ta/T1 bladder cancer. We used three different tissue microarrays with 693 non-muscle invasive urothelial carcinomas from Danish, Swedish, and Spanish patient cohorts with long-term follow-up. Protein expression was measured by immunohistochemistry, and antibody specificity was validated by Western blotting. In the Danish patient cohort, we found the expression of cathepsin E, maspin, Plk1, and survivin to be significantly associated with progression to stage T2 to T4 bladder cancer (for each marker: log-rank test; P < 0.001). Multivariate Cox regression analysis identified cathepsin E (P < 0.001), Plk1 (P = 0.021), maspin (P = 0.001), and survivin (P = 0.001) as independent prognostic markers. Furthermore, maspin, survivin, and cathepsin E expression significantly subgrouped patients already stratified by European Organization for Research and Treatment of Cancer risk scores. Finally, we successfully validated the results in tumors from 410 patients from both Sweden and Spain. We conclude that all four protein markers may have prognostic value in non-muscle invasive bladder cancer for guiding optimal treatment of patients. Additional prospective studies are needed for further validation of the clinical relevance of this marker panel.

Abstract P036: Socioeconomic Status and Risk of Diabetes over 35 Years

Background and aim: The link between low socioeconomic status (SES) and CHD is well established but whether low SES is also an independent predictor for development of diabetes type 2 is not clear. The aim of this study was to investigate whether SES, measured as occupational class, predicted subsequent development of diabetes type 2 over an extended follow-up. Methods: A total of 6941 men 47-55 years old, without prior diabetes, from a population sample of 9998 men, were investigated during 1970-73. Of the men, 23.7% were unskilled workers, 27.2% were skilled workers, 19.7% occupied either a supervisory manual position or were lower officials, 17.9% were officials at an intermediate position, and 11.6% were professionals, executives or senior officials. Follow-up was achieved through the national Swedish patient registry. Results: A total of 900 men (13%) were registered at any time with a diagnosis of diabetes over a 35-year follow-up. Compared with men in the highest occupational class, men with intermediate non-manual occupations had a multiple-adjusted hazard ratio (HR) of 1.10, 95% confidence interval (CI) 0.84-1.44, lower officials and foremen had an HR of 1.37 (1.06-1.78), semiskilled and skilled workers 1.39 (1.08-1.78), and unskilled workers 1.66 (1.30-2.13) after adjustment for smoking at baseline, BMI, blood pressure, serum cholesterol, treatment for hypertension and leisure time physical activity. Conclusions: Low SES is an independent risk factor for long-term risk of diabetes in men, with a 66% independent higher risk in unskilled workers, compared to professionals/senior officials.

A Case of New Delhi Metallo-β-Lactamase 1 (NDM-1)-Producing Klebsiella pneumoniae with Putative Secondary Transmission from the Balkan Region in the Netherlands

New Delhi metallo-beta-lactamase 1 (NDM-1) was first identified in 2008 in a Klebsiella pneumoniae strain from a Swedish patient of Indian origin with a history of medical treatment in a New Delhi hospital for a urinary tract infection ([12][1]). Since then, more such cases in different parts of the

Search for the molecular basis of ultra-rapid CYP2C9-catalysed metabolism: relationship between SNP IVS8-109A&gt;T and the losartan metabolism phenotype in Swedes

To search for a relationship between ultra-rapid metabolism catalysed by cytochrome P450 2C9 (CYP2C9) and its genotypes. DNA from a Swedish ultra-rapid metaboliser patient [losartan metabolic ratio (MR) <0.13] and three healthy Swedes with normal CYP2C9 activity and a MR of about 1 were assessed for variation in the CYP2C9 gene. Direct DNA sequencing was performed for all exons and exon-intron junctions and also for -2100 bp of the 5′-flanking regions of the CYP2C9 gene. This analysis revealed four intronic mutations [single nucleotide polymorphisms (SNPs) 1-4] in the three samples with normal MR while no variation was observed in the ultra-rapid metaboliser. PCR/restriction fragment length polymorphism and allele-specific PCR methods were subsequently developed to screen 85 Swedes and 128 Koreans without CYP2C9*2 or *3. We found a significant relationship between SNP 4 (IVS8-109A>T) and CYP2C9 activity (χ²-test, p=0.011) in the Swedes. Twenty Swedes with the lowest MR were compared with 20 Swedes with the highest MR, revealing a strong association (p00.001) between SNP4 and higher MR. For homozygous SNP 1 (IVS1+83T>C), SNP 2 (IVS2+73T>C), and SNP 3 (IVS6+95A>G), no phenotype and genotype relationships were found, but theMRwas generally higher among the Swedes compared to the Koreans (Mann-Whitney test, p<0.05). We found that the SNP 4 IVS8-109T allele is associated with a higher CYP2C9 MR in healthy Swedish subjects, but further investigations need to be carried out to establish a molecular explanation for ultra-rapid CYP2C9- catalysed metabolism. Haplotype based on SNPs 1-4 did not seem to contribute to variation in the MR of the Korean subjects nor play a role in determining the MR of the Swedish ones.

Emergence and Spread of Antimicrobial-Resistant Pathogens in an Era of Globalization

In recent years, we have witnessed an increased emergence of antimicrobial-resistant (AMR) pathogens. In this era of globalization, international travel has been implicated as a significant risk factor for the acquisition of infections with multidrug-resistant bacteria, including Acinetobacter spp., methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, hypervirulent Clostridium difficile, and Extended-Spectrum-Beta-Lactamase- (ESBL-) producing Enterobacteriaceae [1–4]. The plasmid encoded cefotaximase enzymes CTX-M and the New Delhi metallo-beta-lactamase-1 (NDM-1) represent two excellent examples of the ESBL and carbapenemase that have been rapidly and globally disseminated. In this special issue, M. Elouennass et al. report on high rates of ESBL-producing Enterobacteriaceae and the emergence of carbapenemase-producing isolates in Morocco. The boom in medical tourism has seen patients from developed nations taking up low-cost private medical care in developing countries. This inevitably provides ample opportunity for clinically important AMR pathogens to be acquired and disseminated across geographical borders. A recent example is NDM-1 which was first described in an isolate from a Swedish patient who had previously been hospitalized in New Delhi, India [5]. NDM-1-producing isolates have subsequently been reported across several continents often detected in patients with history of recent medical care in the Indian subcontinent [6]. Preventive measures against nosocomial transmission of AMR pathogens include hand hygiene, environmental decontamination as well as screening and cohorting of patients. Data from the study by J. C. Catano et al., presented in this issue, identifies the diversity of areas of bacterial contamination in a tertiary healthcare setting in a developing country. As stated by the authors “these bacterial reservoirs are a plausible source of infections for patients” and it indicates the need for further research to evaluate strategies for minimizing risk of transmission to patients.

Nanodrugs: optimism for emerging trend of multidrug resistance

Nanodrugs: optimism for emerging trend of multidrug resistance Asad U KhanMedical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India This is with reference to an article published recently in your journal regarding the antibiotic activity of chitosan-coated silver nanoparticles.1 This is an inspiring move towards control of infection caused by multidrug-resistant bacteria which has become a serious problem for clinicians and physicians worldwide.2 At the moment, carbapenems are being used as the drugs of choice to combat infections. However, the emergence of carbapenem resistance has changed current remedial approaches in the management of serious infections. One of the latest enzymes, NDM-1 (New Delhi metallo-β-lactamase-1), first identified in a Swedish patient of Indian origin in 2008,3 has been key in the development of resistance to almost all antibiotics. Infection caused by NDM-1 producers is widespread on the Indian subcontinent,4 and is now emerging in the US and other countries throughout the world.5View original paper by Jena and colleagues.

Cancer Risk Among Patients With Myotonic Muscular Dystrophy

Myotonic muscular dystrophy (MMD) is an autosomal-dominant multisystem neuromuscular disorder characterized by unstable nucleotide repeat expansions. Case reports have suggested that MMD patients may be at increased risk of malignancy, putative risks that have never been quantified. To quantitatively evaluate cancer risk in patients with MMD, overall and by sex and age. We identified 1658 patients with an MMD discharge diagnosis in the Swedish Hospital Discharge Register or Danish National Patient Registry between 1977 and 2008. We linked these patients to their corresponding cancer registry. Patients were followed up from date of first MMD-related inpatient or outpatient contact to first cancer diagnosis, death, emigration, or completion of cancer registration. Risks of all cancers combined and by anatomic site, stratified by sex and age. One hundred four patients with an inpatient or outpatient discharge diagnosis of MMD developed cancer during postdischarge follow-up. This corresponds to an observed cancer rate of 73.4 per 10,000 person-years in MMD vs an expected rate of 36.9 per 10,000 person-years in the general Swedish and Danish populations combined (standardized incidence ratio [SIR], 2.0; 95% CI, 1.6-2.4). Specifically, we observed significant excess risks of cancers of the endometrium (n = 11; observed rate, 16.1/10,000 person-years; SIR, 7.6; 95% CI, 4.0-13.2), brain (n = 7; observed rate, 4.9/10,000 person-years; SIR, 5.3; 95% CI, 2.3-10.4), ovary (n = 7; observed rate, 10.3/10,000 person-years; SIR, 5.2; 95% CI, 2.3-10.2), and colon (n = 10; observed rate, 7.1/10,000 person-years; SIR, 2.9; 95% CI, 1.5-5.1). Cancer risks were similar in women and men after excluding genital organ tumors (SIR, 1.9; 95% CI, 1.4-2.5, vs SIR, 1.8; 95% CI, 1.3-2.5, respectively; P = .81 for heterogeneity; observed rates, 64.5 and 47.7 per 10,000 person-years in women and men, respectively). The same pattern of cancer excess was observed first in the Swedish and then in the Danish cohorts, which were studied sequentially and initially analyzed independently. Patients with MMD identified from the Swedish and Danish patient registries were at increased risk of cancer both overall and for selected anatomic sites.

Perception of quality of care: comparison of the views of patients’ with lung cancer and their family members

To explore potential differences within dyads of patients' with lung cancer and family members' judgment of different aspects of quality of care and relationships between quality of care and personal and health-related characteristics. High quality of care is important for acceptable quality of life in patients in palliative care. If patients are unable to participate in quality of care assessments or decision-making, family members might often act as proxies, despite the complicated nature of their own situation. Cross-sectional survey design. A patient and family member version of the abbreviated questionnaire Quality from Patients' Perspective, with additional items about perceived health and opinions about care, was mailed to members of the Swedish lung cancer Patient Organisation. Wilcoxon's signed rank test was used to identify potential differences within 51 patient-family member dyads' quality of care ratings. Relationships between Quality from Patients' Perspective dimensions and demographic and health-related variables were examined with Spearman's correlations. Patient-family member dyads had high levels of agreement in ratings of perceived reality of quality of care. Family members generally rated the subjective importance of individual items higher than did the patient in the dyad, with significant difference in the dimension 'socio-cultural approach'. Older patients were found to rate the physical-technical conditions higher than younger patients, in relation to perceived reality but not subjective importance. Women family members were found to rate the subjective importance of medical-technical competence, identity-oriented approach and socio-cultural approach significantly higher than men did. Patients with lung cancer and their family members agree in ratings of the perceived reality, but they differ more in ratings of the subjective importance of quality of care. When patients are unable to communicate their preferences, family members' opinions could be used as proxies concerning concrete aspects of quality of care. Concerning more subjective aspects, family members' ratings should be interpreted with precaution, as it could diverge from patients' own opinion. The perceptions of the importance of different aspects of quality of care were less related to health status than were judgments of quality of care received. This might suggest that the care patients received fulfilled neither the patients' nor family members' expectations, which is an important message to healthcare professionals and which would demand further exploration.

Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient

BackgroundMissense mutations in three different genes encoding amyloid-β precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus.MethodsWe combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease.ResultsIn 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb.ConclusionsThis is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy-number of the APP locus.

Gender and Treatment Comparisons in a Cohort Of Patients with Psychiatric Diagnoses

Our purpose in this study was to make group comparisons of the Swedish psychiatric patient cohort called Quality Star. The present study included 1,376 patients, 753 men and 623 women, recruited from 9 outpatient clinics over the space of 6 years. All participants had serious mental illnesses, of which patients with a schizophrenia spectrum disorder were the majority. The 4 aspects studied were consumer satisfaction, life quality, social function, and symptoms. The study had 2 main outcomes: (a) women were more satisfied with the health care and had better functioning than men, (b) patients treated according to the Integrated Care Program had better functioning and less severe symptoms than other patients. The differences between diagnosis groups were as expected.

Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant

The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat.In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model.At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.

Increased risk of end-stage renal disease in individuals with coeliac disease

ObjectiveThe prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for...

Measuring Outcome after Wrist Injury: Translation and Validation of the Swedish Version of the Patient-Rated Wrist Evaluation (PRWE-Swe)

BackgroundThere is a need for outcome measurement instruments for evaluation of disability after trauma. The Patient-Rated Wrist Evaluation (PRWE) is a self-administered region-specific outcome measuring instrument developed for use in evaluating disability and pain of the wrist. The aim of this study is to translate and to cross-culturally adapt the PRWE for use in a Swedish patient population. Moreover, we aim at investigating the PRWE in terms of validity, reliability and responsiveness.MethodsWe performed a translation and cross-cultural adaptation of the PRWE to Swedish (PRWE-Swe), utilising the process recommended by the American Association of Orthopedic Surgeons. A total of 124 patients with an injury to the wrist were included in the study. They filled in the PRWE and the DASH questionnaires at two separate occasions.ResultsReliability of the PRWE in terms of internal consistency (Cronbach's alpha 0.97) and test-retest stability (intraclass correlation coefficient 0.93) were excellent. Face validity and content validity were judged as good. Criterion validity assessed as the correlation between the PRWE and the DASH was also good (Spearman's rho = 0.9). Responsiveness measured by the standardized response mean (SRM) was good with an SRMPRWE of 1.29.ConclusionThis Swedish version of the PRWE is a short and easily understood self-administered questionnaire with good validity, reliability, and responsiveness. Our results confirm that the PRWE is a valuable tool in evaluating the results after treatment of a wrist injury.

Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection

The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.

Mobilizing political will to contain antimicrobial resistance

Vemu Lakshmi is one of several Indian physicians who had long been calling for more to be done about drug resistance. Then, last year, a whirlwind of controversy blew up in her country about the highly resistant superbugs, bacteria containing the so-called NDM-1 enzyme. [ILLUSTRATION OMITTED] Some Indian microbiologists had been flagging the urgent need for micro biological laboratory support for doctors and strict guidelines on antibiotic prescriptions and policies for quite some time;' says Lakshmi, who is professor and head of the Department of Microbiology at Nizam's Institute of Medical Sciences, in Hyderabad. Lakshmi and her colleagues knew that antimicrobial resistance would be the inevitable result of inappropriate use of antibiotics in hospitals and in the community (including sub-therapeutic doses due to ignorance about resistance mechanisms), widespread over-the-counter sales of antibiotics and patients failing to complete their courses of antibiotics. She discussed these problems in detail in an article in the Indian Journal of Medical Microbiology in 2008. The spread of the resistant bacteria in India, Pakistan and the United Kingdom of Great Britain and Northern Ireland was described in a paper published in the Lancet Infectious Diseases in August 2010. NDM-1, or New Delhi metallo-beta-lactamase, was first identified in a Swedish patient who had returned from New Delhi in 2008. Experts were particularly concerned about the fact that the enzyme was found in one of the most commonly encountered bacteria in the human population, Escherichia coli, and that at least one in 10 of the strains containing this enzyme appeared to be resistant to all known antibiotics. Antimicrobial resistance is a global problem that affects all countries. year's World Health on 7 April aims to make governments more aware of the problem and to encourage them to take measures to combat this global threat. [Antimicrobial resistance] is a real public health problem and it is emerging globally and in Europe. We have to do much more about it--both in the World Health Organization (WHO) and also in Member says Zsuzsanna Jakab, WHO Regional Director for Europe. Jakab is well aware that the struggle against antimicrobial resistance in Europe requires continuous vigilance if problems such as drug-resistant tuberculosis are not to get worse. This is the start of a process; we can and have to raise awareness among policy-makers and the public, and follow up with strategies after World Health Day Jakab says. is not the first time WHO has tackled the issue. In 2001, WHO released the Global Strategy for Containment of Antimicrobial Resistance, containing recommendations that countries could customize for their own use. But the launch in Washington DC coincided with the attacks of 11 September 2001 in the United States of (USA) and any momentum was lost in the subsequent turmoil. For Dr Gerald Dziekan, from WHO's Patient Safety Programme, the 2001 initiative nevertheless provided a start for some countries in tackling the problem. [ILLUSTRATION OMITTED] It certainly triggered the development of national plans in some countries, but all in all the response was quite weak in the sense of global awareness and coordinated action,' Dziekan says. One of the challenges governments face in Dziekan's view is enforcing laws banning over-the-counter sales of antibiotics. This is particularly difficult in [low- to middle-income] countries where there are often no doctors to prescribe medicines but people need to get the drugs somehow. But it is also in these countries where the problem is increasingly being felt. Antibiotic resistance is not confined to the emergency rooms of rich countries in Europe and North America according to Anthony So, professor at the Sanford School of Public Policy at Duke University in the USA. …

Emergence of New Delhi Metallo-β-Lactamase, Austria

Emergence of New Delhi Metallo-β-Lactamase, Austria