First-choice Therapy Research Articles

Orális candidiasis, klinikai jellegzetességei, diagnosztikája és kezelése

Candidiasis oris a leggyakoribb opportunista infekció, amelyet egy gomba, a Candia albicans okoz. Mivel a Candida albicans tagja a normális orális flórának, és gyakorisága különböző népcsoportokban 40% körül mozog, a patogenezise még mindig nem teljesen tisztázott.Jelen közlemény célja, hogy összefoglalja e gyakori opportunista infekció potenciális lokális és szisztémás rizikófaktorait, valamint áttekintse a különböző orális klinikai manifesztációit. Számos lokális és szisztémás hajlamosító tényező ismert. Az orális candidiasis előfordulhat akár mint primer, akár secunder infekció. A gomba képes megtapadni a hámon és penetrálni a nyálkahártyát. A lokális prediszponáló faktorok elősegítik a gomba megtapadását és növekedését, míg a szisztémás tényezők negatívan hatnak a természetes vagy szerzett immunitásra, amely felelős a gomba terjedésének kontrolljában. Több klinikai manifesztációja ismert. Előfordulhat akut és krónikus formában. A legsúlyosabb formája a pseudomembranous candidiasis. Ez valódi primer infekció, amely többnyire csak súlyos immunhiányos egyénekben alakulhat ki. A krónikus forma is leggyakrabban AIDS-es betegekben fordul elő. Ilyenkor gyakran találkozhatunk terápia-rezisztens, nagyon hosszú ideje fennálló állhártyás Candida fertőzéssel. A betegség egyéb klinikai formái közé tartozik az erythemas candidiasis, a krónikus nodularis vagy plakkos candidiasis. A leggyakoribb klinikai forma a stomatitis protetika (denture stomatitis). További Candida asszociált szájnyálkahártya betegség a cheilitis angularis és a glossitis mediana rhombica. A klinikai diagnózis a jellegzetes objektív és szubjektív klinikai tünetek alapján legtöbbször egyszerű. A Candida-infekció laboratóriumi identifikálása azonban nem egyszerű, elsősorban azért, mert a Candida tagja a normál szájflórának és így sok egészséges egyénben is kimutatható. A leggyakoribb laboratóriumi diagnosztika technikák közé tartozik a kaparékból nyert citológiai vizsgálat és a gomba tenyésztése. A betegség kezelése komplex és sokszor komoly kihívást jelent az orvos számára. Fontos, hogy feltárjuk és amennyiben lehetséges, elimináljuk a hajlamosító tényezőket. A leggyakrabban használt gombaellenes szerek a polyen és azol csoportba tartoznak. Mivel a legtöbb orális Candida-infekció csak a felszínes nyálkahártya rétegeket érinti, elsőnek lehetőleg helyi gombaellenes kezelést alkalmazzunk. Ez annál is inkább indokolt, mert nagyon sok gombaellenes készítménynek komoly mellékhatásai lehetnek.

5-aminosalicylate-intolerant patients are at increased risk of colectomy for ulcerative colitis.

Although 5-aminosalicylate (5-ASA) is the therapy of first choice in ulcerative colitis (UC), some patients cannot tolerate it because of side effects. Previous reports have not investigated whether 5-ASA intolerance is associated with the risk of colectomy. To investigate the associations between 5-ASA tolerance and colectomy among UC patients METHODS: The data of UC patients who visited any of three hospitals during 2014-2018 in and around Tokyo, Japan, were retrospectively obtained from the medical records. Patients were categorized as (a) tolerant to any 5-ASA compounds ("tolerant to 5-ASA") and (b) patients who were intolerant to one or more 5-ASA compounds leading to refrainment from their further use ("intolerant to 5-ASA"). The association between 5-ASA tolerance and colectomy was examined by Cox proportional hazards model adjusted for sex, age, smoking and extent of colitis. Of 1788 patients, 1684 were "tolerant to 5-ASA" while 104 were "intolerant to 5-ASA". Colectomy was performed in 43 (2.6%) of the patients tolerant to 5-ASA and 12 (11.5%) of the patients intolerant to 5-ASA. After adjusting for all covariates, the risk of undergoing colectomy was higher in the "intolerant to 5-ASA" group than in the "tolerant to 5-ASA" group (hazard ratio: 4.92; 95% confidence interval: 2.58-9.38). Patients in whom 5-ASA was discontinued due to intolerance had a higher risk of undergoing colectomy than patients tolerant to their first, second or third 5-ASA compounds.

A Practical Overview on the Molecular Biology of Meningioma

Meningioma is a common intracranial neoplasm currently classified in 15 histologic subtypes across 3 grades of malignancy. First-choice therapy for meningioma is maximum safe resection for grade I tumors, and surgery plus optional and mandatory adjuvant radiotherapy for grade II and III, respectively, given the increased rate of recurrence even in the event of complete resection. The WHO 2016 histopathologic grading of meningioma has been questioned due to subjectivity and its controversial predictive power for recurrence. Novel DNA methylation profiling has simplified classification into six classes that seem to improve prognostic accuracy. We review five main topics of molecular biology research regarding tumorigenesis and natural history of meningioma from the clinician's perspective: the histopathologic diagnostic features and pitfalls of the current tumor classification; the molecular integrated diagnosis supported by identification of genetic alterations and DNA methylation profiling; the general landscape of the various signaling pathways involved in meningioma formation; the pathogenic theories of the peri-tumoral edema present in meningioma and its therapy implications; and a summarized review on the current treatments and plausible targeted therapies directed to meningioma. It seems likely that molecular assessment will be introduced within the next update of the WHO classification of meningiomas, acknowledging the promising value of DNA methylation profiling. This integrated diagnostic protocol will simplify tumor subtype categorization and provide improved accuracy in predicting recurrence and outcome. Although much effort is being done in identifying key gene mutations, and elucidating specific intracellular signaling pathways involved in meningioma tumorigenesis, effective targeted therapies for recurrent meningiomas are still lacking.

Sonidegib for the Treatment of Advanced Basal Cell Carcinoma.

Basal cell carcinoma (BCC) accounts for almost 80% of skin cancers, and its healthcare workload burden is substantial within dermatology departments. Although most BCCs are small, well-defined tumors amenable of surgery or conservative procedures, in a small proportion of patients, BCCs can progress to an advanced stage including locally advanced BCC. The goal of the clinician in the treatment of BCC should be the right therapeutic approach at diagnosis, and different guidelines propose treatment strategies in order to prevent relapses or disease progression. In case of unresectable and untreatable BCC with radiotherapy, the first-choice medical therapy is Hedgehog-GLI (HH) pathway inhibitors. Sonidegib was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a first-line treatment for adult patients with locally advanced BCC, becoming the second HH pathway inhibitor receiving approval after vismodegib. In this review, data on pharmacology, safety, tolerability, and efficacy of sonidegib are summarized and compared to those of vismodegib. Lastly, indications on the management of advanced basal cell carcinoma based on author’s clinical experience are provided.

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study

BackgroundTreatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects.ObjectiveThe primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism.Methods/designIn this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks.DiscussionThis study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer side-effects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets.Trial registrationThe study was registered on the 19th of March 2020 in the International Clinical Trial Registry, www.clinicaltrials.gov; ID NCT04314193.

Is there still a role for cyclophosphamide in the treatment of systemic sclerosis?

Cyclophosphamide has been the cornerstone of treatment of systemic sclerosis for a long time and is the first-choice therapy for treating systemic sclerosis–associated interstitial lung disease according to the European League Against Rheumatism recommendations on treatment of systemic sclerosis. However, new therapeutic options are emerging, and treatment with cyclophosphamide is hampered by its toxicity and restricted possible treatment duration. This review has a focus on the evidence of efficacy of cyclophosphamide in different aspects of systemic sclerosis and its organ involvements, reviews its toxicity, and will answer the question whether there is still a role for cyclophosphamide in the treatment of systemic sclerosis, taking the evidence and current therapeutic options into account.

Anal Fissure in Children.

Anal fissure is a common clinical problem in children and is defined as a longitudinal tear in the anal canal. The typical presentation is painful defecation and rectal bleeding. The etiology of anal fissure is unknown, but passage of hard stools and increased internal anal sphincter pressure are considered important factors. The treatment is oriented to relieve the spasm of the internal anal sphincter, which prevents healing of the fissure. Conservative management with stool softeners, topical analgesics, and sitz baths is recommended as first-choice therapy. Surgical treatment has been replaced by nonoperative management as definitive therapy, which is associated with a marginally higher success rate than placebo. Most recent studies have focused on nonoperative treatment with glyceryl trinitrate, calcium channel blockers, or botulinum toxin injection treatment. There are a few controlled studies to compare the different nonoperative treatment options in children. Success rates vary between the studies, and there is no clear evidence about which is the optimal nonoperative treatment. A significant recurrence rate has been reported after nonoperative management of anal fissure. It is important to treat constipation to avoid recurrent tears in the anal canal.

Treatment of venous thromboembolism in patients with cancer: from clinical trials to real life

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In the last years, direct oral anticoagulants (DOACs) have been evaluated in a head-to-head comparison with low molecular weight heparin (LMWH) in two randomized trials for the long-term treatment of VTE in patients with advanced cancer. The results of these trials show that DOACs have a similar efficacy profile, but probably higher risk of bleeding, compared to LMWH dalteparin. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation monitoring, they could be attractive alternatives to LMWHs in these setting. The American Society of Clinical Oncology guidelines, published in August 2019, recommend LMWH, edoxaban and rivaroxaban as first-choice therapies for long-term anticoagulation in cancer patients with VTE. However, several practical issues should be considered concerning the long-term use of DOAC treatment in patients with cancer. Major concerns have been highlighted about the gastrointestinal bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions in combination for some specific anticancer therapies. Several studies comparing DOACs with LMWH are currently ongoing to refine our knowledge concerning treatment with DOACs in patients with cancer-associated VTE.

Cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers of the Caucasian population and accounts for 20% of all skin tumours. An S3 guideline of the German Guideline Program in Oncology has been available since 2019. The diagnosis is based on the clinical examination. Excision and histological confirmation is required for all clinically suspicious lesions to allow prognostic assessment and correct treatment. The therapy of first choice is complete excision with histological control of the surgical margin. In cSCC with risk factors such as tumor thickness >6 mm, sentinel lymph node biopsy may be discussed, but there is currently no clear evidence of its prognostic and therapeutic relevance. Adjuvant radiation therapy may be considered in cases of high risk of recurrence and should be tested in cases of inoperable tumors. The indication for electrochemotherapy should also be considered in the treatment of local or locoregional recurrence. The immune checkpoint inhibitor cemiplimab is approved for the treatment of inoperable or metastasized cSCC. In case of contraindications, chemotherapeutic agents, epidermal growth factor receptor (EGFR) inhibitors or palliative radiotherapy can be used. Since the evidence is low in these cases, asystemic therapy should be used preferentially within clinical studies. Follow-up care should be risk-adapted and includes adermatological control, supplemented by ultrasound examinations in high-risk patients.

Device closure of patent ductus arteriosus: analysis of cases in a Bangladeshi centre

Background: Transcatheter closure of Patent ductus arteriosus (PDA) has become the first-choice therapy for closure in patients of any age group. Authors reviewed the outcome of device closure in all age groups starting from neonate to adult.Methods: From December 2014 to December 2019, 440 cases underwent transcatheter closure in a catheterization laboratory of a tertiary level cardiac hospital. Selection criteria were isolated PDA or PDA with associated conditions which can be managed in the same setting by an intervention. Exclusion criteria were proven Eisenmenger syndrome. A retrospective review of outcome and complications were recorded from computerized data records.Results: Age of the patient varied from 10 days to 65 years. The median age was 3 years. Most of the patients were female (63%), weight varied from 1.8 kg to 75 kg. the median weight was 7.5 kg. Isolated PDA cases were 74.77 %. Among syndromes, congenital rubella syndrome was common (7.5%), followed by Down Syndrome (6.36%). The narrowest PDA diameter varied for 1.8 mm - 14 mm with a median of 5 mm. Among duct occluders, 8x6 mm CeraTM was the commonest one used in the study population. Complete occlusion was observed in 99.55% of cases.Conclusions: Transcatheter closure of PDA is considered safe and efficacious in all age groups. It is the gold standard now and replaced surgical option in most of the places.

Diagnosis and Management of Graves' Disease in Thailand: A Survey of Current Practice.

Background The data on clinical practice patterns in the evaluation and management of Graves' disease (GD) are limited in Asia. The aims of this survey were to report the current practices in the management of GD in Thailand and to examine any international differences in the management of GD. Methods Members of the Endocrine Society of Thailand who were board certified in endocrinology (N = 392) were invited to participate in an electronic survey on the management of GD using the same index case and questionnaire as in previous North American and European surveys. Results One hundred and twenty responses (30.6%) from members were included. TSH receptor antibody measurement (29.2%), thyroid ultrasound (6.7%), and isotopic studies (5.9%) were used less frequently to confirm the etiology compared with those in North American and European surveys. Treatment with an antithyroid drug (ATD) was the preferred first choice of therapy (90.8%). Methimazole at 10–15 mg/day with a beta-blocker was the initial treatment of choice. The preferred ATD in pregnancy was propylthiouracil in the first trimester and methimazole in the second and third trimesters, which was similar to the North American and European surveys. Conclusion Ultrasound and isotopic studies will be requested only by a small proportion of Thai endocrinologists. Higher physician preference for ATD is similar to Europe, Latin America, and other Asian countries. Geographical differences in the use of ATD, radioactive iodine, and thyroidectomy exist.

Methanol Poisoning and Its Treatment

Background: Methanol is a toxic alcohol found in illegal liquor, and its poisoning may cause death if not treated timely and properly. In 2018, methanol toxicity in Iran increased dramatically. Regarding the high prevalence of methanol toxicity, its high mortality rate, and the cost of treatment as well as the importance of timely diagnosis in the treatment of this condition, we decided to review methanol toxicity, its signs, symptoms, diagnosis, and treatment.Evidence Acquisition: We searched for articles on reliable databases such as Embase and Medline from January 2018 to May 2018 using the following keywords: “methanol,” “toxic alcohol,” and “ethanol toxicity treatment.”Results: This review discusses how to diagnose methanol toxicity by using clinical signs and symptoms and laboratory examinations; it also suggests new treatments. Meanwhile, we provide alternatives for diagnosis in case of shortages of tests in the emergency department.Conclusion: Diagnosis of ethanol toxicity due to non-specific signs and symptoms, late patient’s referral, and lack of proper history-taking can be very difficult and delay the onset of treatment. There is also no clear scientific evidence as to whether ethanol or fomepizole should be used as the first choice of therapy for methanol toxicity because there is no direct comparison between these two antidotes regarding their effectiveness and safety. The appropriate antidote is chosen depending on the availability, cost, accessibility of hemodialysis, and the physician’s experience. If the therapist does not have enough experience, it is easier to use fomepizole.

ACE-inhibitor/calcium antagonist combination: is this the first-choice therapy in arterial hypertension?

The 2018 ESH/ESC guidelines indicate that the first-choice therapy in the majority of hypertensive patients should be a fixed combination of a drug that blocks the renin-angiotensin-aldosterone system and a calcium antagonist or a diuretic. Evidence from the meta-analysis of controlled clinical trials, however, indicates that the classes of drugs that block the renin-angiotensin-aldosterone system should not be considered equivalent as ACE inhibitors have been clearly shown to outperform AT-1 antagonists in preventing myocardial infarction and total mortality. Moreover, studies such as ASCOT and ACCOMPLISH demonstrate a superiority of the ACE-inhibitor/calcium antagonist association over beta-blocker/diuretic associations and especially towards the ACE-inhibitor/diuretic combination, whereas there is no scientific evidence of efficacy with respect to cardiovascular events on the part of AT-1 antagonist/calcium antagonist combinations. Drugs such as ramipril and amlodipine are undoubtedly the reference molecules within their respective classes as numerous controlled clinical studies have demonstrated their effectiveness on cardiovascular events. It is therefore obvious that the availability of a fixed combination with both molecules is a great opportunity for the therapy of the hypertensive patient, considering also the availability of studies that demonstrate its effectiveness on intermediate endpoints associated with high tolerability. So, in accordance with the 2018 ESH/ESC guidelines, the fixed combination ramipril/amlodipine represents a first choice therapy for hypertension.

Photobiomodulation as an adjuvant in the pharmacological treatment of trigeminal neuralgia. Case report

ABSTRACT BACKGROUND AND OBJECTIVES: Trigeminal Neuralgia causes intense suffering and impaired quality of life. The diagnosis is clinical. Thermography has been proven to be a useful tool, both for confirming and monitoring this neuralgia. Photobiomodulation is being increasingly well documented, specially when associated with the first-choice therapy, which is pharmacotherapy. In this case report, the objective was to investigate the performance of the laser, associated with anticonvulsants, in a patient with trigeminal neuralgia, considering its results from a clinical and thermographic point of view. CASE REPORT: Male patient, 62 years old, presenting idiopathic trigeminal neuralgia, diagnosed 4 years before, being controlled with oxcarbazepine (600mg), divided in 2 daily doses, being the dose doubled in the last year. In the last 4 months, the symptoms worsened with the increase in the drug dosage, generating side effects not supported by the patient. Photobiomodulation was proposed as a complementary treatment, with infrared thermography being performed before and after treatment. After the low-intensity laser therapy protocol, there was a significant improvement, demonstrated both by the patients report and the thermography, maintaining this result in the 6-month control. The dosage was reduced to 300 mg/day, restoring quality of life. CONCLUSION: Low-intensity infrared laser photobiomodulation can be extremely useful when associated with an appropriate drug in the control of idiopathic trigeminal neuralgia, both in the immediate and medium-term outcome.

The PI3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia.

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

Imaging and treatment of idiopathic abdominal cocoon in 9 patients.

The aim of the current study was to investigate the imaging features of abdominal cocoon (AC), the methods of diagnosis and treatment of AC and improve understanding of AC. To do this, the current study retrospectively analyzed the clinical data and imaging findings of nine patients with AC. The clinical manifestations included intestinal obstruction in six out of the nine cases of AC, which included two cases of bowel strangulation and five cases of soft masses in the abdomen. Imaging features of AC included the following: i) Bowel loops were usually present in a fixed cluster; ii) bowel loops were encapsulated partially or totally by a thickening fibrous membrane-like ‘cocoon’; iii) bowel wall thickened in the ‘cocoon’, and the bowel loops and sac adhered; iv) loculated ascites in the ‘cocoon’; v) abnormal clustering of the mesenteric vasculature, hypoplasia of the omentum majus was present or absent; and vi) Ileus occurred in some cases. The features of a plain abdominal X-ray, a gastrointestinal barium meal series and ultrasonography lacked specificity. The results of CT in eight out of nine cases of AC were consistent with the surgical findings. Surgery was the first choice of therapy. All cases were treated surgically, showing that the bowel loops were encapsulated partially or totally by a thickened fibrous membrane. All cases received operations including partial or total excision of the membrane and enterolysis. In conclusion, CT may be highly valuable in the preoperative diagnosis of AC.

Management and outcomes of real-world use of non-vitamin-K oral anticoagulants (NOACs) in patients with atrial fibrillation: experience of adedicated NOAC clinic.

BackgroundCurrent guidelines recommend non-vitamin‑K oral anticoagulants (NOACs) as the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF). The use of drugs in a clinical trial setting differs from that in real-world populations. Real-world data are important to accrue more heterogeneous patient populations with respect to co-morbidities and co-medication use. The aim of this study was to evaluate the use of NOACs in daily practice in a large tertiary hospital in the Netherlands.MethodsA single-centre prospective study was conducted among all patients with AF using a NOAC in the St. Antonius Hospital between 2013 and June 2017. The outcomes were the rates of any bleeding, stroke/transient ischaemic attack, mortality, discontinuation rate and adverse drug reactions.ResultsIn total, 799 patients were enrolled with a mean follow-up of 1.7 years. Mean age was 69.8 (SD ± 11) and 61.2% were male. Mean CHA2DS2-VASc score was 2.8 (SD ± 1.6) and mean HAS-BLED score was 1.4 (SD ± 0.9). Bleeding occurred in 6.0, major bleeding in 1.8, stroke in 1.2 patients per 100 patient-years, and 87 patients (10.9%) died during the follow-up period. Adverse drug reactions were reported by 59 patients (7.4%). Finally, 249 patients (31.2%) reported a temporary interruption and 132 (16.5%) permanent discontinuation of NOAC treatment, of whom 33 (25%) patients switched to a vitamin‑K antagonist.ConclusionsWe observed low rates of bleeding and adverse drug reactions. However, rates of mortality and discontinuation were relatively high. These results could possibly be explained by the real-world nature of the data including higher-risk patients.Electronic supplementary materialThe online version of this article (10.1007/s12471-019-01330-y) contains supplementary material, which is available to authorized users.

Late complications after tracheotomy in the nursing home

Advances in modern intensive care have led to a sharp increase in the number of tracheotomies performed in intensive care units. In contrast to surgical epithelial tracheostomy (ST), a less sturdy stoma is created by means of percutaneous dilation of tracheotomy (PDT). The advantages of a PDT compared to ST are the simpler logistical efforts, associated cost reduction and minimally invasive nature of the process. However, due to variability in airway management, late complications can cause problems, especially in nursing homes. Nursing facilities were given a standardized questionnaire which included information about patient type, tracheotomy type, cannula management protocol, TK management protocol, type of complications occuring at the tracheostoma as well as frequency. Nearly 66 % of the patients were treated with PDT. The complication rates of PDT patients were statistically and significantly higher for all observed complication types compared to the group of patients receiving ST care. 80 % of patients treated with PDT required readmission to clinic for tracheostoma revision, versus 23 % in the ST-patients. A PDT places special demands on the nursing staff in postoperative aftercare. The decision as to which form of tracheotomy is best suited to a particular patient should be made with a multidisciplinary team and depending on the indication. Given the probable long-term nature of the tracheotomy, a surgical tracheostomy should be the therapy of first choice.

First report of acomparative patient-oriented perspective on the use of non-vitamin-K oral anticoagulants or vitamin-K antagonists in atrial fibrillation: patients' experiences, side-effects and practical problems leading to non-adherence.

BackgroundNon-vitamin‑K oral anticoagulants (NOACs) are recommended as the first-choice therapy for stroke prevention in patients with non-valvular atrial fibrillation (AF). However, the lack of monitoring may impact patients’ adherence, and non-adherence to medication is a potential hazard to safe and efficacious use. This is the first report with a ‘comparative patient-oriented perspective’ regarding the use of anticoagulant medication in the NOACs era. Our aim was to compare patients’ self-reported practical problems, adverse events and non-adherence to anticoagulation therapy.MethodsA survey was conducted among patients with AF on either NOACs or vitamin‑K antagonists (VKAs). The outcomes were self-reported non-adherence to anticoagulant medication, and patients’ experiences, adverse events and practical problems correlated with the intake of the drug itself.ResultsA total of 765 patients filled out the questionnaire, of which 389 (50.9%) were on VKAs and 376 (49.1%) on NOACs. Age (70.6 ± 8.8 vs 70.3 ± 9.1 years) and male gender (70.4% vs 64.6%) were similar in the two groups. A significantly higher proportion of VKA users than NOAC users reported having frequent (16.2% vs 3.7%, p > 0.001) or occasional (4.1% vs 1.3%, p > 0.001) practical issues with medication intake. Self-reported non-adherence was significantly higher (24.4% vs 18.1%, p = 0.03) among VKA users. The incidence of self-reported adverse events was similar.ConclusionPatient experiences support the current guideline recommendations for NOACs as the first-choice therapy: NOAC therapy resulted in a higher practical feasibility and better adherence when compared with VKA therapy, with a similar incidence of adverse events in both groups.Electronic supplementary materialThe online version of this article (10.1007/s12471-019-01331-x) contains supplementary material, which is available to authorized users.

Mechanisms of action and clinical applications of anti-obesity drugs currently available in Korea

Over the last 5 years, the Korean Ministry of Food and Drug Safety has approved four anti-obesity drugs for long-term weight management. In this review, the mechanisms of action and clinical applications of lorcaserin, naltrexone/bupropion, liraglutide, and phentermine/topiramate have been clarified. Lorcaserin stimulates proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons in the arcuate nucleus. Naltrexone/bupropion reduces body weight by controlling the hedonic reward system of food intake. The hypophagic effect of liraglutide depends on the direct activation of the proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons and indirect suppression of neuropeptide Y/agouti-related peptide neurons through gammaaminobutyric acid-dependent signaling, with an additional thermogenic effect. Phentermine/topiramate induces weight loss by elevating the norepinephrine levels in the hypothalamus, reducing energy deposition in the adipose tissue and skeletal muscle, and elevating the corticotropin-releasing hormone in the hypothalamus. In patients with high cardiovascular risks or type 2 diabetes mellitus, lorcaserin and liraglutide are appropriate. In patients with mood disorders, naltrexone/bupropion could be considered as the first choice of therapy. Notably, lorcaserin and liraglutide are neutral in the aspect of sleep disorder. In case of obese individuals with obstructive sleep apnea, liraglutide or phentermine/topiramate would be selected as the treatment option. These four drugs should be used after considering the patients' co-morbidities of obesity.