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No abstract available Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Presently, problems exist with the rationale of oral therapy and the nature and indication of topical and accompanying treatment of perioral dermatitis. Objective: Providing the basis to overcome these problems by a quality evaluation of treatment reports and assessment of the consistency of treatment experience. Methods: Sources were Medline (1964–2004), Embase (1966–2004), the Cochrane Central (1971–2004) and 526 ref erences of 3 textbooks, 2 recent reviews and 30 papers on perioral dermatitis. Thirty English and German articles were selected. These studies were evaluated according to principles of evidence-based medicine and related criteria. Evaluation of 28 papers was carried out by the authors and of our own 2 papers by 2 other reviewers. Consistency of results was qualitatively assessed by the authors. Results: There wereonly 2 therapeutic trials of medium-range quality. The other studies were of low quality. Consistency was noted concerning treatment with oral tetracycline (with 1 exception), discontinuation of topical corticosteroids and cosmetics and, to a lesser extent, regarding no therapy. There was inconsistency in respect to topical therapy. Conclusion: The presented data help to interpret and conduct studies on the treatment of perioral dermatitis. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Metastatic breast cancer (MBC) presents an enduring and significant challenge for affected women, requiring sustained commitment over the years. Case Presentation: This paper presents a case of a woman affected by bone and visceral MBC with a very long 20-year survival, excellent quality of life, and high resilience. She is now 51 years old and underwent quadrantectomy for breast cancer in 2005, and in 2013, she developed a recurrence with bone and liver metastases. Despite the widespread stage of the disease with visceral compromise, the patient was treated with a multidisciplinary approach that included surgery, chemotherapy, radiotherapy, hormone therapy, bone target agents, metabolic radiotherapy, and ozone therapy for medication-related osteonecrosis of the jaw. Multidisciplinary management results in a complete clinical and metabolic response to treatment in a visceral metastatic setting. Conclusion: This report supports the possibility of achieving unusual survival outcomes in patients with MBC. This study also highlights the importance of resilience in breast cancer patients who continue to manage their disease and pursue treatment for over 2 decades. Understanding these resilience factors can improve clinical practice and support patients’ long-term care. [ABSTRACT FROM AUTHOR]

Introduction: The correlation between diabetes and stroke has been studied extensively in epidemiological research. Here, we used bibliometric software to visualize and analyze the literature related to diabetic stroke to provide an overview of the current state of research, hotspots, and future trends in the field. Methods: Based on the Web of Science Core Collection (WoSCC) database, we collected studies related to diabetic stroke from 2007 to December 2022. We used CiteSpace (version 6.1.R5), VOSviewer, and Scimago Graphica to create knowledge maps and conduct visual analyses on authors, countries, institutions, cited references, and keywords, and Origin for statistical analysis. Results: We included a total of 5,171 papers on diabetic stroke from the WoSCC database. Overall, there was a steady increase in the number of publications, with a high number of emerging scientists. The USA was the most productive and influential country, which dominated national collaborations. The most common subject category was "neurology." In total, 12 major clusters were generated from the cited references. Keyword analysis showed that keywords related to poststroke injury and treatment are those with the highest burst intensity and latest burst time. Conclusions: Individual disease treatment remains a hot topic, and how to balance acute stroke treatment and glycemic control is currently a difficult clinical problem. At the same time, the mechanism of their interaction and the prevention and treatment of related causative factors remain a hot topic of current and future research. [ABSTRACT FROM AUTHOR]

Aim: The aim of this conference paper was to systematically review the quality of evidence and summarize the findings of clinical trials published after 2002 using fluoride mouth rinses, fluoride gels or foams for the prevention of dental caries.Methods: Relevant papers were selected after an electronic search for literature published in English between 2003 and 2014. The included papers were assessed for their risk of bias and the results were narratively synthesized due to study heterogeneity. The quality of evidence was expressed according to GRADE.Results: A total of 19 papers were included (6 on fluoride mouth rinse, 10 on fluoride gel and 3 on fluoride foam); 6 had a low risk of bias while 2 had a moderate risk. All fluoride measures appeared to be beneficial in preventing crown caries and reversing root caries, but the quality of evidence was graded as low for fluoride mouth rinse, moderate for fluoride gel and very low for acidulated fluoride foam. No conclusions could be drawn on the cost-effectiveness.Conclusions: This review, covering the recent decade, has further substantiated the evidence for a caries-preventive effect of fluoride mouth rinse, fluoride gel and foam, previously established in systematic reviews. The lack of clinical trials free from bias is, however, still a concern, especially for fluoride mouth rinses and fluoride foam. There is also a scientific knowledge gap on the benefit and optimal use of these fluoride supplements in combination with daily tooth brushing with fluoride toothpaste. [ABSTRACT FROM AUTHOR]

Evidence-based strategies for screening, diagnosing and treating alcohol use disorders (AUD) are instrumental in the early and better management of individuals at risk for or suffering from AUD. However, existing guidelines vary and may be biased by conflicts of interests. Unbiased recommendations can be achieved only if sufficient detail is provided on the composition and representativeness of author groups, methodological rigor, handling of potential conflicts of interest and financing. This paper presents the first evidence-based guidelines for AUD from German-speaking countries. These guidelines are based on the work of delegates from a representative sample of 46 scientific societies (mostly medical) from Austria, Germany and Switzerland dealing with AUD. It also included patients and relatives. Recommendations were derived from a standardised hierarchical process involving quality controls drawn from existing guidelines, de novo literature searches and/or expert experience. Potential conflicts of interest were assessed yearly and led to exclusion from voting in specific areas. An overall cost of more than 400,000€ (for alcohol and tobacco guidelines) were exclusively covered by the participating societies and academic institutions. More than 100 recommendations on screening, diagnostics and treatment of AUD are outlined in this paper, and their scientific background is given in the online supplementary material. Tables of aggregated study synopses (in English) and the full version of guidelines (in German) are available (see "Links"). [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Pyoderma gangrenosum (PG) is a rare ulcerating skin disease associated with multiple comorbidities and increased mortality. In recent decades, newer biologics such as interleukin inhibitors have been used to treat PG; however, the literature is scarce, consisting predominantly of case reports and caseseries. The aim of our review was to evaluate the effectiveness and safety of interleukin inhibitors for the treatment of PG in adults. Summary: A literature search was conducted using search terms related to PG and interleukin inhibitors in databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane Library. The study eligibility criteria included patients diagnosed with PG, over the age of 18, and treated with an interleukin inhibitor. Our study included 60 papers describing 81 patients fulfilling the eligibility criteria. The treatment with interleukin inhibitors resulted in 70% (95% CI 59–80%) response and 57% (95% CI 45–68%) complete response rates, and few (4%) mild adverse events, hence supporting the off-label use for the treatment of recalcitrant PG in adults. The response and complete response rates were 59% (17/29) and 38% (11/29) for anakinra, 64% (7/11) and 55% (6/11) for canakinumab, and 79% (27/34) and 71% (24/34) for ustekinumab, respectively. Limitations include publication bias that might have overestimated the efficacy as successful cases responding to treatment are more likely to be reported than nonresponding cases. Additionally, the heterogeneity of the treatment groups does not allow conclusions of superiority or inferiority of the different interleukin inhibitors to be drawn. Further studies are needed to investigate the efficacy of the different interleukin inhibitors and to investigate the importance of underlying disease for treatment response. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy – a combination of intense pulsed light and radiofrequency – as an adjunct treatment to first-line therapies in Hurley stage I and II HS. Methods: The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either an intervention group (IG) or a control group (CG). The IG received topical clindamycin 1% solution combined with 8 additional bi-weekly treatments with LAight® therapy. The CG was treated with topical clindamycin 1% solution only. After 16 weeks, patients entered open-label period B and both groups were treated exclusively with LAight® therapy for an additional 16 weeks (8 sessions). The primary efficacy endpoint was the change in International Hidradenitis Suppurativa Score System (∆IHS4) at week 16 to baseline. Secondary endpoints were DLQI, HiSCR, Pain-NRS, and HADS. Results: In total, from the 88 patients enrolled in RELIEVE, 81 patients were included in the endpoint analysis after period A. After 16 weeks of treatment, the ∆IHS4 of the group treated with the combination of LAight® therapy and topical clindamycin 1% solution was −7.2 ± 6.7 (−60.0%), which was significantly higher in magnitude than the ∆IHS4 in the group treated with clindamycin 1% solution alone (−1.8 ± 5.6, −17.8%, p < 0.001). Secondary endpoints, including other clinical scores as well as patient-reported outcomes, confirmed that the efficacy of the combined treatment was superior to monotherapy. Conclusion: The results of the primary endpoint analysis of period A of the RELIEVE study show that the combined therapy with LAight® and topical clindamycin 1% solution, resulted in a significantly higher decrease in disease severity and an improvement of quality of life in comparison to topical clindamycin 1% solution monotherapy. Treatment was well tolerated, and side effects were all mild and transitory. These data speak for the implementation of the combined treatment as a first-line therapy in Hurley stage I and II HS. LAight® therapy as long-term monotherapy (results from period B), will be analyzed in a consecutive paper. [ABSTRACT FROM AUTHOR]

Europe's growing awareness of gaps in its healthcare provision is not being matched by an increase in remedial action – despite the rich transformative potential of new approaches to data. The new availability of data offers policymakers tools that would allow Europe's huge investments in health to be far better spent, by being properly targeted. The result would be far better health for far more Europeans. But that requires a step that most European policymakers have not been ready to take. They need to cooperate so that the data can be shared and its full value realised. This paper explores the potential and the challenges that stand in the way of mobilising health data for wider health benefits. This paper goes on to summarise the results of a survey on how different components of the healthcare sector perceive the opportunities from mobilising data effectively, and the barriers to doing so. The responses demonstrated a widespread genuine will to promote research and innovation, and its take-up, for the betterment of healthcare. There was strong appreciation of the merits of data sharing and readiness – under the right circumstances – to share personal health data for research purposes and to undergo genetic sequencing. This paper also suggests the strategic direction that should influence policy formation. The solution can be found without changing the EU treaties, which already provide an adequate base for cooperation. Properly handled, the problems facing European healthcare can be turned into major assets for Europe and make it easier for citizens to have equal access to high-quality care through the meaningful use of digital innovations. [ABSTRACT FROM AUTHOR]

Background: The first International Consensus Conference for Advanced Breast Cancer (ABC1) took place 10 years ago in November 2011. The rationale was – and still is – to standardize treatment of advanced breast cancer (ABC) based on the available evidence and to ensure that worldwide all breast cancer patients receive adequate treatment and access to new therapies. Rationale for the Manuscript: The 6th International Consensus Conference for ABC (ABC6) took place from November 4 to 6, 2021 and was the first in a purely online format, due to the COVID-19 pandemic. In the present manuscript, a working group of German breast cancer experts comments on the voting results of the ABC6 panelists regarding their applicability for routine clinical practice in Germany. Method: The ABC6 votes mainly include modified or new statements. With regard to all statements not modified for the ABC6 consensus, the German experts refer to the published paper of the ABC5 consensus. The German experts base their comments on the current recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Mamma). Topics: ABC6 focused on new treatment options and their implications for clinical practice. Optimal therapy sequencing for example was one of the issues. To solve the challenge of a more individualized treatment, precision medicine is fundamental. Oligometastatic disease, brain metastases and adequate supportive and palliative care were also addressed. Of special interest was the treatment of inoperable locally advanced breast cancer, which was discussed as a separate topic. As in previous years, patient advocates from around the world were an integral part of the ABC6 conference and had a major input into the consensus. [ABSTRACT FROM AUTHOR]

Background: In neonatal respiratory distress syndrome (RDS) and acute RDS (ARDS) mechanical ventilation is often necessary to manage hypoxia, whilst protecting the lungs through lower volume ventilation and permissive hypercapnia. Mechanical ventilation can, however, induce or aggravate the lung injury caused by the respiratory distress. Helium, in a gas mixture with oxygen (heliox), has a low density and can reduce the flow in narrow airways and allow for lower driving pressures. Objectives: The aim of this study was to review preclinical and clinical studies of the use of heliox ventilation in acute lung injury associated with respiratory failure. Methods: A systematic search was executed in the PubMed and EMBASE databases, with search terms referring to ARDS or an acute lung injury condition associated with respiratory failure and the corresponding intervention. Results: A total of 576 papers were retrieved. After the majority had been excluded 20 papers remained, of which 6 articles described animal models (3 paediatric; 3 adult animal models) and 14 were clinical studies, of which 12 described paediatric patient populations and 2 adult patient populations. In both paediatric and adult animal models, heliox improved gas exchange while allowing for less invasive ventilation in a wide variety of models using different ventilation modes. Clinical studies show a reduction in the work of breathing during heliox ventilation, with a concomitant increase in pH and decrease in PaCO2 levels compared to oxygen ventilation. Conclusions: Although evidence so far is limited, there may be a rationale for heliox ventilation in ARDS as an intervention to improve ventilation and reduce the work of breathing. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Non-contrast computed tomography of the kidneys, ureters, and bladder (CT KUB) is the investigation of choice for renal colic; however, radiation exposure can be a concern. Aims: The study aimed to investigate the diagnostic accuracy of low dose (LD) and ultra-low dose (ULD) CT of the urinary tract for detection of urinary tract stones in patients with renal colic. Methods: A Cochrane style systematic review of the literature from 1995 to 2017 was carried out. Literature search and data extraction were conducted by 2 reviewers. Specificity and sensitivity values were calculated for LD (<3.5 mean radiation dose [mSv]) and ULD (<1.9 mSv) CT separately. Results: A total of 12 studies were included following screening. A total of 1,529 patients were included in the review (475 in the LD group and 1,054 in the ULD group). Using standard dose CT KUB as the reference standard, the sensitivity of LD CT KUB ranged from 90 to 98% and specificity from 88 to 100%. The sensitivity of ULD CT KUB ranged from 72 to 99% and the specificity ranged from 86 to 100%. The diagnostic accuracy for LD CT was 94.3% and for ULD CT was 95.5%. Conclusions: LD and ULD CT KUB provide effective methods of identifying urinary tract stones. High diagnostic accuracy, sensitivity, and specificity are maintained despite significant radiation dose reduction in comparison to standard dose CT. [ABSTRACT FROM AUTHOR]

Background and Summary: The management of endometrial cancer, in an ever-older population with considerable comorbidity, remains a challenge for gynecological and radiation oncologists. Key Message: The present paper reviews literature data on treatment options for endometrial cancer patients unfit for surgery. [ABSTRACT FROM AUTHOR]

Extraintestinal manifestations (EIM) have become an important source of morbidity and disability as well as an identified risk factor for an unfavorably course of disease in inflammatory bowel diseases (IBD). Therefore, efforts have been put into a more global and interdisciplinary management of IBD patients in collaboration with rheumatologists, dermatologists, and ophthalmologists. A real therapeutic success has also been obtained with a more "systemic" IBD treatment associated with the development of monoclonal antibodies against TNF alpha and biological agents derived from the treatment of rheumatological disease (also called biological Disease-Modifying Antirheumatic Drugs). The prevalence of these EIM remains too low to undergo randomized controlled trials with this specific focus and therefore the evidence relies on case series and experts' opinions, which lowers the level of evidence. After a careful review of the most recent literature, this paper aims to update the reader on the latest therapeutic management of IBD patients with EIM. [ABSTRACT FROM AUTHOR]

Fertility-sparing surgery (FSS) is an established concept within operative gynaecology. Intraoperative ultrasound (IOUS) has the potential of assessing lesion margins, allowing complete resection with minimal damage to the surrounding healthy tissue and could potentially play a major role in FSS for benign or malignant gynaecological pathologies. In this paper, we review the current literature on the use of IOUS in gynaecological FSS. We also propose technical guidance on the IOUS during FSS. The findings of this review demonstrate that IOUS can assist in the safe resection of disease with high rates of completion, low rates of recurrence and without damage to the nearby healthy reproductive organs. Improved training in transvaginal ultrasonography and minimal access surgery are likely to facilitate the application of IOUS in FSS. [ABSTRACT FROM AUTHOR]

Despite improvements in dental caries levels since the widespread introduction of fluoride toothpastes, it is still a disease which is considered to be a priority in many countries around the world. Individuals at higher risk of caries can be targeted with products with a high fluoride concentration to help reduce the amount and severity of the disease. This paper compares guidance from around the world on the use of products with a high fluoride concentration and gives examples of how guidance has been translated into activity in primary care dental practice. A rapid review of electronic databases was conducted to identify the volume and variation of guidance from national or professional bodies on the use of products with a high fluoride concentration. Fifteen guidelines published within the past 10 years and in English were identified and compared. The majority of these guidelines included recommendations for fluoride varnish use as well as for fluoride gels, while a smaller number offered guidance on high fluoride strength toothpaste and other vehicles. Whilst there was good consistency in recommendations for fluoride varnish in particular, there was sometimes a lack of detail in other areas of recommendation for other vehicles with a high fluoride concentration. There are good examples within the UK, such as the Childsmile project and Delivering Better Oral Health, which highlight that the provision of evidence-based guidance can be influential in directing scarce resources towards oral health improvements. Policy can be influenced by evidence-based national recommendations and used to help encourage dental professionals and commissioners and third-party payers to adopt higher levels of practices aimed at oral health improvement. [ABSTRACT FROM AUTHOR]

The primary aim of this work is to present the available evidence that toothpastes containing >1,500 ppm fluoride (2,500-2,800 and 5,000 ppm F) provide an additional caries preventive effect on root caries lesions in elderly patients compared to traditional dentifrices (1,000-1,450 ppm F). The secondary aim of this paper is to discuss why high fluoride dentifrices in general should perform better than traditional F-containing toothpaste. When examining the few studies that have considered the preventive benefits of high fluoride products on root caries the relative risk appears to be around 0.5, and the risk can thus be halved by exchanging traditional F-containing toothpaste for toothpaste containing 5,000 ppm F. There is reasonable evidence that high fluoride dentifrices significantly increase the fluoride concentration in saliva during the day and the fluoride concentration in plaque compared to traditional F toothpaste. Furthermore, the use of toothpaste with 5,000 ppm F significantly reduces the amount of plaque accumulated, decreases the number of mutans streptococci and lactobacilli and possibly promotes calcium fluoride deposits to a higher degree than after the use of traditional F-containing toothpaste. [ABSTRACT FROM AUTHOR]

Background: Our laboratory previously reported that imatinib mesylate (IM) has an inhibitory effect on two retinoblastoma (Rb) cell lines in vitro.Aims: The purpose of this project was to determine the immunoexpression of platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and c-Abl in 61 human samples of Rb to determine if IM-sensitive receptors are present. Additionally, this paper seeks to establish a correlation between the expression of PDGFR, c-Abl and the histopathological prognosis. Methods: Sixty-one paraffin-embedded Rbs were collected from the Henry C. Witelson Ocular Pathology Registry. PDGFR-α, PDGFR-β and c-Abl immunostaining was performed according to the protocol provided by Ventana Medical System Inc. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve. Results: Overall, c-Abl expression was identified in 50 out of 61 specimens (81.97%), PDGFR-α was identified in 20 out of 60 specimens (33.33%) and PDGFR-β expression was identified in 57 out of 61 specimens (93.44%). Histopathological prognosis was not correlated with immunoreactivity except in the case of PDGFR-β. Conclusions: Rb is a cancer that expresses PDGFR-α, PDGFR-β and c-Abl, which are known targets of IM. These markers may be responsible for the documented therapeutic effect of IM on Rb cell lines. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lenvatinib (LEN) is a multikinase inhibitor with antiangiogenic properties recently approved in radioactive iodine-refractory differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma in combination with everolimus. LEN-treated patients frequently have adverse events (AEs) that generally require such dose modifications, including drug discontinuation. Hypertension, diarrhea, weight loss, proteinuria, fatigue, and palmar-plantar erythrodysesthesia are reported among the most frequent AEs, often leading to discontinuations or dose modifications. This paper reports a case series focusing on the role of the immediate multidisciplinary approach to manage AEs. [ABSTRACT FROM AUTHOR]

While in the past surgery for prolactinomas was a competitive option to medical treatment with dopamine agonists, to date the indications for operations are restricted to only a few specific situations. However, if a patient is intolerant to medical treatment or if the drugs are not sufficiently effective in terms of lowering prolactin levels or tumor shrinkage, surgery should always be considered. In microprolactinomas, operations can achieve excellent prolactin normalization rates. In tumors difficult to treat, the combination of surgical tumor resection and long-term medical treatment supports better control of the disease. The individual indications, results, techniques, and complications of operations for prolactinomas are briefly reviewed in this paper. [ABSTRACT FROM AUTHOR]

Objective: For people with aphasia (PWA) and their significant others, narratives are intricately intertwined with quality of life, culture, and social participation. This paper reports stories told by bilingual people with aphasia (bPWA), describing the events or consequences of a stroke on their lives. Patients and Methods: Six participants with chronic mild-moderate anomia (mean age 70 years) spontaneously produced a narrative recounting their personal experience of stroke in their native language (Greek) and in their second language (English). All bPWA had learned English in early adulthood upon migration from Greece to Australia, not through formal teaching but on the job (e.g., in the factory). The bPWA had lived in Australia for 46 years (average) and were less than 4 years post-stroke. Results: Narratives in the two languages underwent quantitative (number of propositions, noun/verb tokens) and qualitative analyses (ratings of coherence, ratings of clarity). Most bPWA produced coherent "tellable" stories despite disruptions in language because of aphasia. Overall, stories were better told (length, complexity of content, temporal-causal sequencing, reference) in Greek – their native language. Conclusion: The results have implications for policy-makers providing health and welfare services to ageing immigrant populations. The findings are also relevant to other countries that have large immigrant populations of stroke survivors. [ABSTRACT FROM AUTHOR]

Background: At present there is a substantial uncertainty regarding the extent and nature of autism spectrum disorder (ASD) and bipolar affective disorder (BPAD) co-occurrence due to disparate findings in previous studies. This paper aimed to find and review original studies on co-occurrence rates of ASD with BPAD, assess them, synthesize the findings in a systematic way, present an overview and make recommendations for future research. Methods: Systematic literature searches were performed using several databases. Selected articles had to describe an original study that provided prevalence and/or incidence analysis on ASD co-occurring together with BPAD. Results and Conclusion: A significant minority of patients (7%) with ASD suffers from BPAD. An accurate detection of co-occurring ASD and BPAD can lead to a more targeted treatment and improve the patients' functioning and quality of life. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Dental caries is considered as the most common polymicrobial oral disease in the world. With the aim of developing alternative approaches to reduce or prevent the decay, numerous papers showed the potential anticaries activity of a number of natural products. The natural products with anticaries effects are selected from e.g. food, beverages, flowers or traditional herbs. Most of the effective components are proven to be polyphenol compounds. Many of the natural products are studied as antibacterial agents, while some of them are found to be effective in shifting the de-/remineralization balance. However, the mechanisms of the anticaries effects are still unclear for most of the natural products. In the future, more efforts need to be made to seek novel effective natural products via in vitro experiment, animal study and in situ investigations, as well as to enhance their anticaries effects with the help of novel technology like nanotechnology. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Endoscopic third ventriculostomy (ETV) provides a physiological restoration of cerebrospinal fluid and a shunt-free option for hydrocephalus children. Continuous developments in techniques and instruments have improved ETV as the first-line treatment. This paper focuses on the recent advances in surgical techniques, instruments, predictive models, imaging tools, and new cohort studies. The efficacy, safety, indications, and remaining challenges of ETV are discussed. More patients undergo ETV with a better outcome, identifying a new era of hydrocephalus treatment. Deeper understanding of ETV will improve a better shunt-free survival for pediatric hydrocephalus patients. [ABSTRACT FROM AUTHOR]

Background: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.Methods: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included.Results: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.Conclusions: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders. [ABSTRACT FROM AUTHOR]

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this “expert best practice” paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos­copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40–70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined. The main periprocedural adverse events are exacerbation of asthma symptoms and increased cough and sputum production. Occasionally, atelectasis has been observed following the procedure. The long-term safety of BT is excellent. An optimized BT responder profile – i.e., which specific asthma phenotype benefits most – is a topic of current research. [ABSTRACT FROM AUTHOR]

Background/Aims: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. Methods: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson’s trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2’-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. Results: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. Conclusion: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper was to perform a systematic review and, when feasible, a meta-analysis of randomized controlled trials (RCT) which used benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD), or both.Methods: Keyword searches were conducted for identifying RCT comparing BZD and AD, and/or placebo in the treatment of depression, using electronic databases from their inception up to April 2017. We selected reports of RCT in which BZD were compared to AD and/or placebo in the treatment of adult patients with a primary diagnosis of depressive disorder or anxious depression. When feasible, data were subjected to meta-analysis.Results: A total of 38 studies met the criteria for inclusion and were then included in the systematic review. Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we submitted data on response rate from 22 RCT, considering BZD versus placebo (8 comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons). There was a lack of significant differences as to response rate between BZD and placebo, as well as between BZD and TCA. Analysis of individual studies disclosed that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD were significantly more effective than placebo and as effective as TCA.Conclusions: BZD are a therapeutic option in anxious depression and there are no indications that AD are preferable. There is a pressing need for RCT of adequate methodological quality and follow-up comparing BZD to second-generation AD and placebo in anxious depression. [ABSTRACT FROM AUTHOR]

Intervention approaches to aphasia differ in different countries. The aim of this paper is to give an overview of the situation in the Czech Republic. The following topics are summarized: (1) Czech logopedics in aphasiology; (2) the assessment of aphasia; (3) the treatment of aphasia; (4) Czech aphasiologic material; (5) the qualification of clinical logopedists, and (6) regulations of aphasiologic care. Czech is a very intricate language, both phonetically and grammatically. The prevalence of consonants appearing in long sequences (a whole sentence can be constructed purely of consonants) makes it difficult to pronounce. The strong inflecting character with hundreds of grammatical forms for each inflected word makes it difficult to use correct morphology and syntax. These facts make Czech a real challenge both for aphasics and logopedists. An overview of aphasia tests and treatment methods used in the Czech Republic, as well as conditions of logopedic care are given. The paper will allow comparison with the situation in other countries. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Public health genomics is a new field that brings the findings of research in genetic and molecular technologies together with public health. The purpose of this paper is to examine the interface between this new emerging field and that of public health intelligence. We describe the possible areas of integration between genomics and public health, suggesting a future potential role for the Public Health Observatories. Methods: A small group comprising of a public health geneticist and representatives from Public Health Observatories met and discussed the ways in which the public health information and intelligence community might contribute to the developing agenda of public health genomics. Results: The results of the deliberations are presented in this paper, and a combination of short, medium and longer term possibilities are described. Also, necessary changes and additions to routinely collected data are proposed. Conclusions: The emerging field of public health genomics has implications for the collection, management and analysis of routine data. The benefits of this will accrue over time, but changes need to be made now in order to make the best use of these developments. A possible supporting action plan for the development of public health genomics within Public Health Observatories is proposed. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractBackground:This paper examines the current status of research on the efficacy and effectiveness of antidepressants. Methods:This paper reviews four meta-analyses of efficacy trials submitted to America’s Food and Drug Administration (FDA) and analyzes STAR*D (Sequenced Treatment Alternatives to Relieve Depression), the largest antidepressant effectiveness trial ever conducted. Results:Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure as though it was their primary measure of interest. The STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions:The reviewed findings argue for a reappraisal of the current recommended standard of care of depression.Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractBackground:State laws in the USA mandate that blood be drawn from all newborn infants to screen for health-threatening conditions. These screening assays consume only a small portion of the blood samples, which are collected on filter paper (‘Guthrie’) cards. Many states archive unused blood spots, often in unrefrigerated storage. Objectives:While individual RNA transcripts have been identified from archived neonatal blood spots, no study to date has performed quantitative analysis of archived blood spot RNA. Methods:We demonstrate that RNA can be isolated and amplified from newborn blood spots stored unfrozen for as long as 9 years, and can be analyzed by microarray and qPCR. Results:Microarray assays of archived neonatal blood spots consistently detected 3,000–4,000 expressed genes with correlations of 0.90 between replicates. Blood spot mRNA is amenable to qPCR and we detected biologically relevant expression levels of housekeeping and immune-mediating genes. Conclusions:These experiments demonstrate the feasibility of using blood spots as a source of RNA which can be analyzed using quantitative microarray and qPCR assays. The application of these methods to the analysis of widely collected biological specimens may be a valuable resource for the study of perinatal determinants of disease development.Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractIn this paper, we present a multiaxial system for psychodynamic diagnosis, which has attained wide usage in Germany in the last 10 years. First we will discuss the 4 operationalized psychodynamic diagnostics (OPD) axes: illness experience and treatment assumptions, relationships, mental conflicts, and structure, then clinical applications will be outlined. Focus psychodynamic formulations can be employed both with inpatients and with outpatients. Studies show good reliability in a research context and acceptable reliability for clinical purposes. Validity will be separately summarized as content, criterion, and construct validity. Validity studies indicate good validity for the individual axes. Numerous studies on the OPD indicate areas of possible improvement, for example for clinical purposes the OPD should be more practically formulated.Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Comments on several papers on evaluation of treatment outcome of different addiction services. Variables associated with treatment outcome that can be described as subjective patient variables, such as motivation for treatment; Evaluation of variables associated with treatment outcome and variables which concern the structure and organization of addiction services; Paper which addresses the most complex area of treatment outcome evaluation.

This paper focuses on exploring the association between the patient’s perception of his own interpersonal behaviour on the one hand, and that of the therapist’s behaviour and of helping alliance on the other hand. A cross-sectional study was conducted, including 83 patients from substance dependence programs in The Netherlands. They completed the Helping Alliance Questionnaire (HAQ) and the Interpersonal Check List (ICL). Results indicate that the patient’s perception of the therapeutic alliance, and his perception of his own and of the therapist’s interpersonal behaviour are three separate domains, each playing their role in the context of the therapeutic relationship. Helping Alliance scores are predicted by both the patient’s (complaisance) and the therapist’s interpersonal behaviour (dominance). We conclude that patient’s cognitions about himself and about his therapist do contribute significantly to the perception of the therapeutic relationship. Limitations to the study are discussed, as well as some clinical implications. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This paper reviews current ideas relating to oral fluoride retention after topical applications of various fluoride preparations. The oral fluoride reservoirs, which serve as a store for fluoride, gradually releasing its content into saliva, will be discussed. The present paper also deals with fluoride kinetics in the oral cavity. The answer to the title of the paper has, however, not yet been found but remains a goal for researchers studying caries prophylaxis worldwide in the search for possible ways of increasing and improving oral fluoride retention. [ABSTRACT FROM AUTHOR]

Structural changes in the organization of drug treatment services in the northwest of England during the early 80s provided a unique opportunity to study a group of opiate addicts who were turned away from treatment. This paper reports on 60 opiate addicts who were abstinent at follow-up (2–3 years after their original referral). For the majority of subjects, any treatment received in the intervening period had been from a range of local, non-specialist treatment providers, including: general practices (n = 24) and local hospitals (n = 32). The subjects had also received assistance from non-statutory agencies (n = 35). Informal sources of support were drawn upon in the form of friends, family, and voluntary agencies. Social acceptance, legal problems, financial difficulties, and imprisonment were frequently cited as motivational factors that led to abstinence. At follow-up, improvements were reported in personal relationships and family circumstances, although there was less progress in relation to employment, finances, and housing. Increased involvement with the criminal justice system was significantly associated with a greater use of treatment services at follow-up. This paper presents the treatment and non-treatment pathways that led to abstinence amongst this group of opiate addicts. It also points to the importance of including non-treatment samples in evaluations of treatment interventions.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Placebo effects are often attributed to clinical interactions and contextual factors that affect expectations of the patient about the treatment and result in symptom changes. The prevailing conceptualization consists of an undifferentiated placebo response that needs to be minimized in controlled investigations and maximized in clinical practice. However, treatment outcome is the cumulative result of the interaction of several classes of variables with a selected treatment: living conditions (housing, nutrition, work environment, social support), patient characteristics (age, sex, genetics, general health conditions, personality, well-being), illness features and previous therapeutic experience, self-management, and treatment setting (physician's attitude and attention, illness behavior). Such variables may be therapeutic or countertherapeutic, and are unlikely to be simply additive. In certain patients their interactive combination may lead to clinical improvement, whereas in other cases it may produce no effect, and, in a third group, it may lead to worsening of the condition. Maximizing patients' expectations does not necessarily result in sustained effects and, in due course, may actually lead to worsening of the condition (violation of expectations). In this paper, we outline a multifactorial conceptual model that may have implications for the design of clinical trials as well as for clinical practice, with special reference to psychopharmacology and psychotherapy. The effects of drug treatment may be potentiated by specific nonpharmacological treatment strategies, and this synergism may disclose significant differences against placebo. Medical outcomes may be unsatisfactory not because technical interventions are missing, but because our conceptual models and thinking are inadequate. [ABSTRACT FROM AUTHOR]

Background/Aims: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and β-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemoradio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64CuCl2 and SI113 on human GBM cell lines with variable p53 expression. Methods: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64CuCl2. Results: We demonstrate here, that i) 64CuCl2 is able to induce a time and dose dependent modulation of cell viability (with different IC50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. Conclusions: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64CuCl2 in GBM cells. [ABSTRACT FROM AUTHOR]

Introduction: The authors of this paper assessed the surgical management and outcome of renal cancers when tumor thrombus extended into the inferior vena cava (IVC). Methods: From 2000 to 2015, 46 radical nephrectomies were performed on patients with tumor thrombus in the IVC. The mean age of the patients was 60 ± 11 years. Radical nephrectomy and thrombectomies were performed in a single session. There were 18 level-IV, 23 level-III, and 5 level-II tumor thrombi. The operations were performed using cardiopulmonary bypass in 14 patients, while deep hypothermic cardiac arrest was carried out in 4 cases. Results: The mean size of the tumors was 9.4 ± 3.5 cm. Histology showed the tumor stages to be pT3b in 21cases, pT3c in 22, and pT4 in 3 patients. The mean follow-up period of the patients was 3.6 ± 3.0 years. During the follow-up period, local recurrence was observed in 7 patients, while distant metastases occurred in 8 cases. The median time to progression was 37 ± 27 months. The 5-year overall survival was 43.7%. Conclusions: Radical nephrectomy and thrombectomy provided reasonable long-term survival for patients with renal cancer and IVC thrombus. However, tumor progression was detected in 41.6%. The presence of tumor thrombus had a negative effect on tumor progression and survival. [ABSTRACT FROM AUTHOR]

Antiseptics, with a broader spectrum of antimicrobial efficacy, lower risk of antibiotic resistance development, and minimal collateral damage to host tissues, are important alternatives to control the bioburden in wounds. Povidone iodine (PVP-I), in use for several decades, has the broadest spectrum of activity, a persistent antimicrobial effect, an ability to penetrate biofilms, and a lack of acquired or cross-resistance. It demonstrates good skin tolerance and low cytotoxicity. However, some reports on PVP-I have raised concerns over allergy, ineffective penetration, and toxic effects on host cells. The majority of these concerns are based on in vitro or rodent wound studies with diverse study designs and outcomes; these results may not be directly applicable in the clinical reality in humans. In this paper, we discuss the efficacy and safety of PVP-I and outline its place in wound healing in Asia, based on an appraisal of recent literature and clinical practice across the region. [ABSTRACT FROM AUTHOR]

Prophylactic gonadectomy in young adult women with complete androgen insensitivity syndrome (CAIS) to avoid development of an invasive testicular germ cell tumor (TGCT) is currently advised in most centers. However, women with CAIS increasingly question the need of this procedure. In order to provide optimal counseling and follow-up of these women, insight in the mechanisms underlying TGCT development in androgen insensitivity syndrome (AIS), data regarding the incidence of TGCT in AIS adults specifically, and an overview of existing and novel screening tools for in situ and invasive neoplastic lesions are crucial. The current knowledge regarding these topics is revised in this paper. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET). AdVince includes the gene promoter from human chromogranin A for selective replication in neuroendocrine cells, miR122 target sequences for reduced liver toxicity, and a cell-penetrating peptide in the capsid for increased infectivity of tumor cells and optimized spread within tumors. This paper describes the preclinical evaluation of AdVince on freshly isolated human gastrointestinal NET cells resected from liver metastases and freshly isolated human hepatocytes as well as in fresh human blood. AdVince selectively replicates in and kills NET cells. Approximately 73-fold higher concentration of AdVince is needed to induce a similar level of cytotoxicity in NET cells as in hepatocytes. AdVince did not activate complement or induce considerable amount of proinflammatory cytokines or chemokines in human blood. The data presented herein indicate that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a severe progressive and irreversible lung disease. Novel antifibrotic drugs that slow disease progression are now available. However, many issues regarding patient management remain unanswered, such as the choice between available drugs, their use in particular subgroups and clinical situations, time of treatment onset, termination, combination or switch, or nonpharmacologic management. To guide Swiss respiratory physicians in this evolving field still characterized by numerous areas of uncertainty, the Swiss Working Group for interstitial and rare lung diseases of the Swiss Respiratory Society provides a position paper on the diagnosis and treatment of IPF. [ABSTRACT FROM AUTHOR]

The hemolytic uremic syndrome (HUS) is one of the thrombotic microangiopathies and it consists of the triad of nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The atypical form of HUS (aHUS) is related to causative mutations in complement genes. Some conditions act as a trigger for aHUS in individuals that have a genetic background predisposing to complement activation. Interferon β is a recombinant-protein therapy approved to treat multiple sclerosis (MS), and can be a causative agent in the occurrence of HUS through anti-angiogenic activity. In this paper, we briefly review aHUS clinical and genetic characteristics. Furthermore, we present a case of a 48-year-old woman, diagnosed with MS and treated with INFβ-1b from 2008. In December 2015, she presented with asthenia and loss of muscular strength in the legs and she quickly developed aHUS. Our case suggests that INFβ is a possible triggering factor for HUS. [ABSTRACT FROM AUTHOR]

There have been many efforts to collect drug treatment demand data in the last decades, but only few organisations worked on international comparable instruments. This paper describes such an attempt organised under the auspices of the Council of Europe in the late 80s, beginning of the 90s. Both the developed protocol as well as its implementation in various European cities are presented. Between 1993 and 1999, a comparative research project to annually compile data and trends on European level was carried out. Data quality issues and methodological problems are highlighted. The paper notes the value and success of the treatment demand indicator, but claims for further improvements and a combined use with other indicators and qualitative information. Some spin-off and follow-up projects are summarised.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An international task force made up of a panel of 16 experts was mandated to review and objectively evaluate all aspects of chronic venous disease of the leg. All available publications on chronic venous disease of the leg from 1983 to 1997 were identified through computerized search. Three different screenings were then performed in order to select only relevant papers providing moderate to strong scientific evidence. Final conclusions and further therapeutic recommendations were made based on these publications. Compression, medications, local therapies, sclerotherapy and surgery are the existing therapeutic options for which the following recommendations can be made. Compression: Properly applied bandages both fixed and stretched have been shown to be effective. Compression stockings may be used. Compression needs to be in excess of 35 mm Hg. Medications: Although preliminary results have shown a beneficial effect of several vasodilators and oral micronized purified flavonoid fraction, the evidence for the efficacy of medications on venous ulcer healing is still limited and further studies are required before recommendations can be made. There is no evidence to routinely administer antibiotics. Local therapies have an as yet unproven adjunctive role. Sclerotherapy is unlikely to be effective unless there is superficial venous insufficiency, in which it may have an as yet unproven role. Surgery: Patients with active venous ulcer and sapheno-femoral or sapheno-popliteal junction incompetence benefit from surgical treatment. In the absence of reflux or following deep vein thrombosis, there is no evidence to support surgical treatment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of neurodegenerative impairment in elderly people. Clinical characteristics include short-term memory loss, confusion, hallucination, agitation, and behavioral disturbance. Owing to evolving research in biomarkers, AD can be discovered at early onset, but the disease is currently considered a continuum, which suggests that pharmacotherapy is most efficacious in the preclinical phase, possibly 15–20 years before discernible onset. Present developments in AD therapy aim to respond to this understanding and go beyond the drug families that relieve clinical symptoms. Another important factor in this development is the emergence of precision medicine that aims to tailor treatment to specific patients or patient subgroups. This relatively new platform would categorize AD patients on the basis of parameters like clinical aspects, brain imaging, genetic profiling, clinical genetics, and epidemiological factors. This review enlarges on recent progress in the design and clinical use of antisense molecules, antibodies, antioxidants, small molecules, and gene editing to stop AD progress and possibly reverse the disease on the basis of relevant biomarkers. Highlights of the Study: The heterogeneous and multifactorial nature of Alzheimer's disease needs new therapeutic approaches. Precision medicine aims to tailor treatment to specific patients or patient subgroups. Various tailored approaches, especially genomic editing techniques, represent a promising new therapy for Alzheimer's disease. It is highly likely that precision medicine is most efficacious at the preclinical stage of Alzheimer's disease. [ABSTRACT FROM AUTHOR]