Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using $\sim$2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant $(p<5 \times 10^{-8})$ or suggestive associations $(p<4 \times 10^{-7})$ were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding $(p<4 \times 10^{-7})$. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

Nurses ' adherence to hand: promoting and hygiene guidelines hindering factors

Bakgrund: Uppkomsten av vårdrelaterade infektioner (VRI) är ett globalt problem. Den vanligaste smittvägen är via personalens händer. Bra handhygien är väsentligt för att minska VRI. Med bättre följsamhet till handhygien kan uppkomsten av VRI minskas, därför har forskning om följsamhet till handhygien och faktorer som inverkar, stort betydelse. Syfte: Syftet var att sammanställa och beskriva aktuell forskning om sjuksköterskors följsamhet till handhygien och vilka faktorer främjar respektive hindrar följsamheten till handhygien. Metod: En litteraturöversikt som baserades på artiklar publicerade de senaste fem åren, från länder som följer Världshälsoorganisationens (WHO) handhygieniska riktlinjer. Sexton artiklar valdes efter kvalitetsgranskning för analys och beskrivning. Artiklarna bearbetades med innehållsanalys. Resultat: Sjuksköterskors följsamhet till handhygien var låg. Följande främjande faktorer identifierades: handhygien efter patientkontakt, materialtillgång, förebilder, utbildning, verbala och visuella påminnelser, positiva individuella attityder, kvinnlig könstillhörighet, yrkesgrupp, specialitet, patientens skydd, arbetskultur och samhällets inställning till handhygien. Följande hindrande faktorer identifierades: hög arbetsbelastning, bristande utbildning, kunskapsbrist, individuella attityder, hudpåverkan, materialtillgång, arbetskultur och samhällets inställning till handhygien, manlig könstillhörighet, yrkesgrupp, specialitet. Slutsats: Enligt resultat rekommenderas: samspelet med kollegor och patienter, stöd av teamarbete ledare, förebilder, materialtillgång, utbildning, påminnelser, intervention med tillgång till information, stöd, resurser och möjligheter för regelbunden kunskapsuppföljning, motivera till handhygien före patientkontakt, involvera patienter.Background: The emergence of healthcare-associated infections (VRI) is a global problem. The most common route of transmission is via the staff's hands. Good hand hygiene is essential for reducing VRI. With better adherence to hand hygiene, the emergence of VRI is reduced, therefore, research on adherence to hand hygiene and factors affecting, big importance. Aim: The aim was to compile and describe current research on nurses ' adherence to hand hygiene and what factors promote or hinder the adherence to hand hygiene. Method: A literature review based on articles published in the last five years, from countries that follow the World Health Organisation (WHO) hand hygiene guidelines. Sixteen articles were selected for quality review of analysis and description. The items were processed with content analysis. Results: nurses ' adherence to handhygiene was low. Promoting factors was handhygiene after patient contact, materials access, role models, training, verbal and visual reminders, positive individual attitudes, gender, profession, specialty, patient protection, work culture and society's attitudes to handhygiene. Limiting factors: high workload, lack of education, lack of knowledge, individual attitudes, skin effects, materials access, work culture and society's attitudes to handhygiene, sex, profession, specialty. Conclusion: According to the results is folowing recommended : the interaction with colleagues and patients, support of team work leaders, role models, materials access, education, reminders, intervention with access to information, support, resources and opportunities for regular knowledge track, justify to handhygiene prior to patient contact, involve patients

Nurses ' adherence to hand: promoting and hygiene guidelines hindering factors

Bakgrund: Uppkomsten av vårdrelaterade infektioner (VRI) är ett globalt problem. Den vanligaste smittvägen är via personalens händer. Bra handhygien är väsentligt för att minska VRI. Med bättre följsamhet till handhygien kan uppkomsten av VRI minskas, därför har forskning om följsamhet till handhygien och faktorer som inverkar, stort betydelse. Syfte: Syftet var att sammanställa och beskriva aktuell forskning om sjuksköterskors följsamhet till handhygien och vilka faktorer främjar respektive hindrar följsamheten till handhygien. Metod: En litteraturöversikt som baserades på artiklar publicerade de senaste fem åren, från länder som följer Världshälsoorganisationens (WHO) handhygieniska riktlinjer. Sexton artiklar valdes efter kvalitetsgranskning för analys och beskrivning. Artiklarna bearbetades med innehållsanalys. Resultat: Sjuksköterskors följsamhet till handhygien var låg. Följande främjande faktorer identifierades: handhygien efter patientkontakt, materialtillgång, förebilder, utbildning, verbala och visuella påminnelser, positiva individuella attityder, kvinnlig könstillhörighet, yrkesgrupp, specialitet, patientens skydd, arbetskultur och samhällets inställning till handhygien. Följande hindrande faktorer identifierades: hög arbetsbelastning, bristande utbildning, kunskapsbrist, individuella attityder, hudpåverkan, materialtillgång, arbetskultur och samhällets inställning till handhygien, manlig könstillhörighet, yrkesgrupp, specialitet. Slutsats: Enligt resultat rekommenderas: samspelet med kollegor och patienter, stöd av teamarbete ledare, förebilder, materialtillgång, utbildning, påminnelser, intervention med tillgång till information, stöd, resurser och möjligheter för regelbunden kunskapsuppföljning, motivera till handhygien före patientkontakt, involvera patienter.Background: The emergence of healthcare-associated infections (VRI) is a global problem. The most common route of transmission is via the staff's hands. Good hand hygiene is essential for reducing VRI. With better adherence to hand hygiene, the emergence of VRI is reduced, therefore, research on adherence to hand hygiene and factors affecting, big importance. Aim: The aim was to compile and describe current research on nurses ' adherence to hand hygiene and what factors promote or hinder the adherence to hand hygiene. Method: A literature review based on articles published in the last five years, from countries that follow the World Health Organisation (WHO) hand hygiene guidelines. Sixteen articles were selected for quality review of analysis and description. The items were processed with content analysis. Results: nurses ' adherence to handhygiene was low. Promoting factors was handhygiene after patient contact, materials access, role models, training, verbal and visual reminders, positive individual attitudes, gender, profession, specialty, patient protection, work culture and society's attitudes to handhygiene. Limiting factors: high workload, lack of education, lack of knowledge, individual attitudes, skin effects, materials access, work culture and society's attitudes to handhygiene, sex, profession, specialty. Conclusion: According to the results is folowing recommended : the interaction with colleagues and patients, support of team work leaders, role models, materials access, education, reminders, intervention with access to information, support, resources and opportunities for regular knowledge track, justify to handhygiene prior to patient contact, involve patients

Obstructive sleep apnea a hidden national disease: Identifying and guiding patients with suspected sleep apnea in primary care

Bakgrund: Obstruktiv sömnapné (OSA) är en vanlig och mycket utbredd sjukdom förknippad med betydande hälsoproblem, samsjuklighet och mortalitet. De flesta vuxna med OSA är utan diagnos och behandling. Primärvårdens distriktssköterskor spelar en viktig roll vid identifiering och vägledning av patienter med misstänkt OSA. Syfte: Syftet var att beskriva distriktsköterskans erfarenheter av att identifiera och vägleda patienter med misstänkt OSA inom primärvården. Metod: En kvalitativ ansats i form av en kvalitativ manifest innehållsanalys genomfördes där sju distriktssköterskor intervjuades. Analysprocessen genomfördes enligt Graneheim och Lundmans innehållsanalys. Resultat: I studien framkom fem kategorier: att möta patienten, att ställa rätt frågor, anhörig som motivator, att vidta åtgärder och att samverka med övrig vård. Distriktssköterskorna beskrev att de mötte patienterna med misstänkt OSA oftast antingen via telefonrådgivning eller på diabetesmottagningen. Deltagarna i studien belyste att det var viktigt att ställa rätt frågor till patienter och känna till de vanliga tecknen på OSA. Det framkom även att anhöriga hade en viktig roll vid identifiering av patienter med misstänkt OSA och fungerade som motivator. I studien upptäcktes även strävan efter att vägleda patienter med misstänkt OSA. Slutsats: För att underlätta arbete med OSA patienter i primärvården behövs forskning med fokus på distriktssköterskor samt gemensamma riktlinjer för utredning av patienter med misstänkt OSA anpassade för primärvårdspersonal.Background: Obstructive sleep apnea (OSA) is a common and very spread disease associated with significant health problems, comorbidity and mortality. Most adults with OSA are without diagnosis and treatment. Primary care district nurses play an important role in identifying and guiding of patients with suspected OSA. Purpose: The purpose was to describe the district nurse's experience of identifying and guiding patients with suspected OSA in primary care. Method: A qualitative approach in the form of qualitative manifest content analysis was conducted where seven district nurses were interviewed. The analysis process was conducted according to Graneheim and Lundman's content analysis. Result: The study revealed five categories: to meet the patient, to ask the right questions, relative as motivator, to take workarounds and to interact with other care. District nurses described that they met the suspect OSA patients most often by telephone counseling or at the diabetes reception. The participants in the study illuminated the importance of how to ask the right questions to patients and to know the common signs of OSA. It was also found that relatives had an important role in identifying of patients with suspected OSA and they worked as motivators. The study also identified the strain for guiding patients with suspected OSA. Conclusion: In order to facilitate work with OSA- patients in the primary care, research is needed which is focusing on district nurses and common guidelines for investigating of patients with suspected OSA adapted for primary care staff

Obstructive sleep apnea a hidden national disease: Identifying and guiding patients with suspected sleep apnea in primary care

Bakgrund: Obstruktiv sömnapné (OSA) är en vanlig och mycket utbredd sjukdom förknippad med betydande hälsoproblem, samsjuklighet och mortalitet. De flesta vuxna med OSA är utan diagnos och behandling. Primärvårdens distriktssköterskor spelar en viktig roll vid identifiering och vägledning av patienter med misstänkt OSA. Syfte: Syftet var att beskriva distriktsköterskans erfarenheter av att identifiera och vägleda patienter med misstänkt OSA inom primärvården. Metod: En kvalitativ ansats i form av en kvalitativ manifest innehållsanalys genomfördes där sju distriktssköterskor intervjuades. Analysprocessen genomfördes enligt Graneheim och Lundmans innehållsanalys. Resultat: I studien framkom fem kategorier: att möta patienten, att ställa rätt frågor, anhörig som motivator, att vidta åtgärder och att samverka med övrig vård. Distriktssköterskorna beskrev att de mötte patienterna med misstänkt OSA oftast antingen via telefonrådgivning eller på diabetesmottagningen. Deltagarna i studien belyste att det var viktigt att ställa rätt frågor till patienter och känna till de vanliga tecknen på OSA. Det framkom även att anhöriga hade en viktig roll vid identifiering av patienter med misstänkt OSA och fungerade som motivator. I studien upptäcktes även strävan efter att vägleda patienter med misstänkt OSA. Slutsats: För att underlätta arbete med OSA patienter i primärvården behövs forskning med fokus på distriktssköterskor samt gemensamma riktlinjer för utredning av patienter med misstänkt OSA anpassade för primärvårdspersonal.Background: Obstructive sleep apnea (OSA) is a common and very spread disease associated with significant health problems, comorbidity and mortality. Most adults with OSA are without diagnosis and treatment. Primary care district nurses play an important role in identifying and guiding of patients with suspected OSA. Purpose: The purpose was to describe the district nurse's experience of identifying and guiding patients with suspected OSA in primary care. Method: A qualitative approach in the form of qualitative manifest content analysis was conducted where seven district nurses were interviewed. The analysis process was conducted according to Graneheim and Lundman's content analysis. Result: The study revealed five categories: to meet the patient, to ask the right questions, relative as motivator, to take workarounds and to interact with other care. District nurses described that they met the suspect OSA patients most often by telephone counseling or at the diabetes reception. The participants in the study illuminated the importance of how to ask the right questions to patients and to know the common signs of OSA. It was also found that relatives had an important role in identifying of patients with suspected OSA and they worked as motivators. The study also identified the strain for guiding patients with suspected OSA. Conclusion: In order to facilitate work with OSA- patients in the primary care, research is needed which is focusing on district nurses and common guidelines for investigating of patients with suspected OSA adapted for primary care staff

Pimecrolimus, a topical calcineurin inhibitor used in the treatment of atopic eczema

INTRODUCTION: Pimecrolimus , a calcineurin inhibitor, is a non-steroidal treatment option in patients aged ≥ 2 years with mild-to-moderate atopic eczema (AE). It was approved as a viable therapeutic option by the FDA in 2001 and in the European Union a year later in 2002. Calcineurin inhibitors inhibit the synthesis of inflammatory cytokines released from T cells and mast cells. In contrast to corticosteroids, calcineurin inhibitors act specifically on proinflammatory cells. Pimecrolimus shows comparative efficacy to mild topical corticosteroids and a special antipruritic effect. Furthermore, examinations of the systemic absorption of pimecrolimus implicated no systemic immunosuppression. In 2006, the FDA set a black box warning in the packaging materials of pimecrolimus alluding to the risk of skin malignancy or lymphomas due to theoretical consideration. AREAS COVERED: The authors provide a review of pimecrolimus as a treatment for AE. Specifically, the authors present the pharmacokinetic and pharmacodynamic information on pimecrolimus and also review its efficacy. The authors also discuss pimecrolimus' safety and tolerability profile. EXPERT OPINION: Pimecrolimus represents a valuable part of active and proactive therapy in AE. That being said, the long-term safety of topical calcineurin inhibitors remains to be investigated. Given the results from experimental photocarcinogenicity studies, effective sun protection should be employed during the therapy, although an increased risk for skin malignancies and lymphomas was not found in recent studies. Pimecrolimus should be considered as an alternative therapeutic approach in AE treatment management going along with a corticoid-sparing effect