Family Medicine and Primary Care

Post-COVID healthcare reform in India: What to expect? Soham D Bhaduri Journal of Family Medicine and Primary Care 2020 9(11):5427-5431 COVID-19 has exposed the fault lines of India's public health system. The pandemic can be a useful window of opportunity to undertake public healthcare reforms that are long due. Such reforms are, however, constrained by the path-dependent characteristics of private healthcare in India. Measures taken to expand healthcare during the pandemic appear unlikely to sow the seeds of successful path transformation, and may rather reinforce the private sector dominated trajectory. Policymakers must introduce a bold set of pro-public healthcare reforms during the pandemic, which can then be incrementally built upon through securing legitimacy and support.

Why COVID-19 pandemic builds a convincing case for investing in 'Young Physician Leaders (YPL)' Paramdeep Singh Journal of Family Medicine and Primary Care 2020 9(11):5432-5434 There are pressing issues that are plaguing healthcare systems across the world (especially in the lower-middle-income countries), which comprise low-quality care, affordability, accessibility, poor infrastructure, violence against healthcare personnel, deficiency of physicians and healthcare staff. COVID-19 has put an immense physical and mental strain on the young physicians who are at the forefront in fighting this pandemic. This has lead to an increase in incidences of burnout among young doctors, which adversely impacts the quality of healthcare, patient well-being and satisfaction. The present-day medical training typically creates solo medical experts; but, modern-day management of patients and organisations require team-work and leadership. To profoundly alter the way the young physicians work and for creating physician leaders for the future, leadership training ought to commence during the medical school.

A low-cost solution for converting existing stethoscope into tele-stethoscope in resource-constrained setting for COVID-19 pandemic Sumit Kalra, Preeti Mutreja, Amit Goyal, Abhinav Dixit Journal of Family Medicine and Primary Care 2020 9(11):5435-5436 In the present scenario of COVID-19, there has been a sudden surge in demand for tele- consultancy. Such measures require resources to support the system. Replacement of conventional equipment used in a clinic with digital equipment is not feasible due to their cost and scalability issues. The authors developed a simple low-cost (almost zero cost) method to convert a conventional stethoscope into a tele-stethoscope. Such a simple modification can be useful in periphery wherein doctors are still not available and the growing number of patients would require a diagnosis of the chest conditions.

COVID-19: Lab medicine expect due respect Amrita Ghosh Journal of Family Medicine and Primary Care 2020 9(11):5437-5438

Preparing for a COVID-19 pandemic: Redefining roles of multidisciplinary team in a large tertiary hospital in Rajasthan Abhay Elhence, Binit Sureka, Mahendra Kumar Garg, Pankaj Bhardwaj, Tanuj Kanchan, Arvind Sinha, Pradeep Kumar Bhatia, Vijaya Lakshmi Nag, Nikhil Kothari, Naveen Dutt, Suryanarayanan Bhaskar, Vibhor Tak, NR Bishnoi, Sanjeev Misra Journal of Family Medicine and Primary Care 2020 9(11):5439-5444 Through this manuscript, we would like to share our experience with building a COVID hospital, allocating duties, planning and managing supplies during COVID-19 pandemic. This manuscript is prepared by the Doctors of various specialties with vast experience involved in actual planning of the infrastructure and resources. This comprehensive manuscript will help teams to prepare and train, stockpile necessary equipment and prepare their staff to deal with current crisis if there is a surge in infected cases.

COVID-19 reinfection: Linked possibilities and future outlook Ekta Krishna, Vineet Kumar Pathak, Reshma Prasad, Hannah Jose, M Mohan Kumar Journal of Family Medicine and Primary Care 2020 9(11):5445-5449 SARS-CoV-2 is the third major coronavirus epidemic to affect humans. There had been multiple instances of patients turning positive after recovering from SARS-2-CoV infection. Though many different theories emerge, false positive RT-PCR is logically the foremost cause and there is a general consensus that during quarantine re-infection from outside seems unlikely when strictly adhered to. As many new strains emerge worldwide during the course of on-going pandemic, the chances of re-infection cannot be ignored as it may contribute to false negative RT-PCR test results. SARS-2-CoV though a novel virus, is phylogenetically similar to SARS-like CoV with around 79% similarity. Studies on immunological response to these infections suggest that antibodies formed after infection confers immunity only for a short period of time before it starts to wane. Also studies on SARS-CoV-2 suggest that antibody formation and longevity of immunity in an individual is dependent on the strain of coronavirus, its severity and age of the person infected. All these considerations demand reviewing the treatment duration, discharge criteria, appropriate use of imaging techniques and importance of risk communication and health education to those recovered.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel Sanjay Kalra, AK Das, G Priya, S Ghosh, RN Mehrotra, S Das, P Shah, S Bajaj, V Deshmukh, D Sanyal, S Chandrasekaran, D Khandelwal, A Joshi, T Nair, F Eliana, H Permana, MD Fariduddin, PK Shrestha, D Shrestha, S Kahandawa, M Sumanathilaka, A Shaheed, AA Rahim, A Orabi, A Al-ani, W Hussein, D Kumar, K Shaikh Journal of Family Medicine and Primary Care 2020 9(11):5450-5457 Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Mapping of Health Technology Assessment (HTA) teaching and training initiatives: Landscape for evidence-based policy decisions in India Rinshu Dwivedi, Ramesh Athe, Sanghamitra Pati, Krushna C Sahoo, Debdutta Bhattacharya Journal of Family Medicine and Primary Care 2020 9(11):5458-5467 Demographic transitions accompanied with epidemiological shifts are affecting many countries around the globe. These apprehensions have raised the concern for constructing and sustaining healthcare systems especially among resource-constrained low- and middle-income-countries (LMICs) such as India. Introducing Health-Technology-Assessment (HTA) in the educational initiatives could support planners and policy-makers in formulating evidence-based-decision-making along with tackling inequalities/inefficiencies and promoting cost-effectiveness in resource allocation. A mapping exercise has been undertaken for examining the feasibility and implementation of HTA curriculum in the existing courses in India. To gain best possible insight on HTA curriculum, a situational analysis was conducted using systematic search strategy through search engines such as Google, Google Scholar, ProQuest and PubMed. Currently, seventy-one institutes in India are offering one or more courses through regular mode at undergraduate/postgraduate/diploma-certificate/doctorate-level pertaining to Medical-technology (MT), Biostatistics (BS), and Health-economics (HE). MT was offered in 37 institutes (52.12%), followed by BS in 23 (32.39%), and HE in nine (12.67%). Only two institutes (2.81%) are offering certificate-courses on HTA, mainly confined in virtual modules. This review reveals noticeable gaps in the existing curriculum in India and necessitates a novel academic initiative by introducing HTA in a full-fledged manner. Reforms in the research and educational initiatives need to be brought for promoting awareness regarding HTA. The application of domain needs to be widened from the field of health-policy formulators to research and teaching. This should be further strengthened with the strong academic collaborations to generate replicable findings, address challenges, and offer solutions for existing threats to HTA.

Managing pregnancy in COVID-19 pandemic: A review article Vinita Singh, Pragati Trigunait, Sagarika Majumdar, Rajeshwari Ganeshan, Rajshree Sahu Journal of Family Medicine and Primary Care 2020 9(11):5468-5473 The outbreak Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a highly contagious and lethal beta coronavirus SARS-CoV-2, which has spread fast to encroach the entire globe and hence declare pandemic. Pregnancy alters body physiology and immune systems, can have worse effects of some respiratory infections and due to limited research and published data we still are in dilemma of appropriate management guidelines This article covers the updated guidelines for infection prevention and control (IPC), screening, sampling, antenatal visit schedules, risk scoring, triaging, supportive care, delivery, postpartum care and care of the newborn. This article aims to provide up-to-date information as per recent guidelines of various association which would serve as guidance in managing pregnant women and newborn with suspected or confirmed COVID-19. All the published papers till date, NCPRE, WHO Interim guidelines, RCOG, FOGS GCPRI, Medical Council of India, ICMR, MOFHW, CDC, ACOG guidelines are referred to compile this article to reach to a conclusion of evidence based management of pregnant ladies during COVID-19 pandemic. This article covers the not only infection prevention and control (IPC) guidelines, but also screening and sampling guidelines, antenatal visit schedules, risk scoring, triaging but also in-patient supportive care, delivery, postpartum care and care of the newborn. Data are very limited and hence very difficult to accurately define clinical management strategies and needs to be constantly updated.

Novel coronavirus (COVID-19) and its potential G.I. manifestation: A review Amar Deep, Kamlendra Verma, Suchit Swaroop, Ajay Kumar, Sumit Rungta Journal of Family Medicine and Primary Care 2020 9(11):5474-5479 The outbreak of the new coronavirus in Wuhan, Chinese Hubei City (COV-2) was also known as COVID-19 and has spread to more than 213 countries, zones or territories worldwide, and is an emergency of international public health with no antiviral drugs or vaccines; and, also, the presencouragement of the disease has become a global public health emergency. This novel coronavirus is now the seventh member of the coronaviridae family, known for infecting humans and showing evidence of causing gastric symptoms, and has the potential to be transmitted through the fecal-oral route according to a new report published online by physicians at Shanghai Jiao Tong University (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro. 2020.02.054). Here we identify the efforts to compile and disseminate the COVID-19 epidemiological information on Its potential G.I. Demonstration of news media and social networks, and few newspapers recently published. Physicians should know, how GI manifestation discussed in different publications to suspect CORONA virus infection in that patients who does not have any upper and lower respiratory tract symptom and intervein to discuss the disease severity and duration. It will increase the threshold of suspicion of physician toward Covid-19 disease.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Orthopaedic Trauma

Acknowledgment No abstract available

In Memoriam: David Gershuni, MD (1938 - 2020) No abstract available

Distal Femur Replacement Versus Surgical Fixation for the Treatment of Geriatric Distal Femur Fractures: A Systematic Review Objectives: The management of geriatric distal femur fractures is controversial, and both primary distal femur replacement (DFR) and surgical fixation (SF) are viable treatment options. The purpose of this study was to compare patient outcomes after these treatment strategies. Data Sources: PubMed, Embase, and Cochrane databases were searched for English language articles up to April 24, 2020, identifying 2129 papers. Study Selection: Studies evaluating complications in elderly patients treated for distal femur fractures with either immediate DFR or SF were included. Studies with mean patient age <55 years, nontraumatic indications for DFR, or SF with nonlocking plates were excluded. Data Extraction: Two studies provided Level II or III evidence, whereas the remaining 28 studies provided Level IV evidence. Studies were formally evaluated for methodological quality using established criteria. Treatment failure between groups was compared using an incidence rate ratio. Data Synthesis: Treatment failure was defined for both SF and arthroplasty as complications requiring a major reoperation for reasons such as mechanical failure, nonunion, deep infection, aseptic loosening, or extensor mechanism disruption. There were no significant differences in complication rates or knee range of motion between SF and DFR. Conclusions: SF and DFR for the treatment of geriatric distal femur fractures demonstrate similar overall complication rates. Given the available evidence, no strong conclusions on the comparative effectiveness between the 2 treatments can be definitively made. More rigorous prospective research comparing SF vs. DFR to treat acute geriatric distal femur fractures is warranted. Level of Evidence: Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.

Surgical and Nonoperative Management of Olecranon Fractures in the Elderly: A Systematic Review and Meta-Analysis Objectives: The aim of this comparative effectiveness study was to perform a meta-analysis of adverse events and outcomes in closed geriatric olecranon fractures, without elbow instability, after treatment with surgical or nonoperative management. Data Sources: PubMed, Web of Science, and Embase databases. Study Selection: Articles were included if they contained clinical data evaluating outcomes in patients ≥65 years of age with closed olecranon fractures, without elbow instability, treated surgically, or with nonoperative management. Data Extraction: Data regarding patient age, olecranon fracture type, fracture union, adverse events, reoperation, elbow range of motion, and surgeon and patient reported outcome measures were recorded according to intervention. The interventions included for analysis were tension band wire fixation, plate fixation, or nonoperative management. Data Synthesis: Separate random effects meta-analyses were conducted for each outcome according to intervention. Prevalence and 95% confidence intervals were calculated for dichotomous variables, whereas weighted means and confidence intervals were calculated for continuous variables. Conclusions: Comparable outcomes were achieved with surgical or nonoperative management of olecranon fractures in geriatric patients. Surgical intervention carried a high risk of reoperation regardless of whether plate or tension band wire fixation was used. Functional nonunion can be anticipated if nonoperative treatment is elected in low-demand elderly patients. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Topical Vancomycin Powder Decreases the Proportion of Staphylococcus aureus Found in Culture of Surgical Site Infections in Operatively Treated Fractures Objectives: To determine whether patients with operatively treated fractures and surgical site infection after use of topical vancomycin powder have a lower proportion of Staphylococcus aureus infections than patients who did not receive topical vancomycin powder. Design: Retrospective cohort study. Setting: Level I trauma center. Patients: Treatment group: 10 of 133 patients (145 fractures) with surgical site infections who received intrawound vancomycin powder at the time of wound closure for fracture fixation. Control group: 175 patients who sustained deep surgical site infections during the same period but did not receive vancomycin powder. Intervention: Vancomycin powder or no vancomycin powder. Main Outcome Measurement: Proportion of patients' cultures positive for S. aureus. Results: The proportion of cultures positive for S. aureus was significantly lower in patients with surgical site infection who received vancomycin powder than in those who did not receive vancomycin powder (10% [1 of 10 patients in the treatment group] vs. 50% [87 of 175 patients in the control group]; P = 0.02). A trend was observed for a lower proportion of methicillin-resistant S. aureus (0% vs. 23%; P = 0.12). Conclusions: Vancomycin powder might alter the bacteriology of surgical site infections and decrease the proportion in culture of the most common organism typically present after fracture surgery infection. These findings suggest that the application of vancomycin powder might change the bacteriology of surgical site infections when they occur, regardless of the effect on overall infection rates. Although our bacteriology results are clinically and statistically significant, these findings must be confirmed in larger randomized controlled trials. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Vancomycin Powder Use in Fractures at High Risk of Surgical Site Infection Objectives: To determine if the use of intrawound vancomycin powder reduces surgical-site infection after open reduction and internal fixation of bicondylar tibial plateau, tibial pilon, and calcaneus fractures. Design: Retrospective analysis. Setting: Level I trauma center. Patients: All fractures operatively treated from January 2011 to February 2015 were reviewed; 583 high-risk fractures were included, of which 35 received topical vancomycin powder. A previously published prospectively collected cohort of 235 similar high-risk fractures treated at our center from 2007 through 2010 served as a second comparison group. Intervention: Topical vancomycin powder at wound closure. Main Outcome Measurements: Deep surgical-site infection. Analyses used both univariate comparison of all patients and 1:2 matching analysis using both nearest neighbor and propensity-based matching. Results: Compared with a control group of fractures treated during the same time period without vancomycin powder, the infection rate with vancomycin powder was significantly lower [0% (0/35) vs. 10.6% (58/548), P = 0.04]. Compared with our previously published historical infection rate of 13% for these injuries, vancomycin powder was also associated with significantly decreased deep surgical-site infection (0% vs. 13%, P = 0.02). These results agreed with the matched analyses, which also showed lower infection in the vancomycin powder group (0% vs. 11%–16%, P ≤ 0.05). Conclusions: Vancomycin powder may play a role in lowering surgical-site infection rates after fracture fixation. A larger randomized controlled trial is needed to validate our findings. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery Objectives: To determine whether using topical vancomycin powder in fracture surgery may result in low levels of vancomycin in the serum and not result in nephrotoxicity. Design: Prospective observational at a single site as a substudy of the VANCO trial. Setting: Single, large urban level I trauma center. Patients/Participants: Fifty-eight patients with tibial plateau and pilon fractures randomized to the treatment arm at the principal investigator's site. Intervention: Topical vancomycin powder (1000 mg) applied directly in the wound over all metal implants at the time of wound closure. Main Outcome Measurements: Serum vancomycin levels at 1 hour and 6–8 hours after surgery. Secondary outcomes included serum creatinine before surgery, a day after surgery, and at 2 weeks postoperatively and complete blood count at 2 weeks postoperatively. Results: Except in 2 patients who also received intravenous vancomycin, none of the study patients had detectable (>5 µg/mL) serum vancomycin levels at 1 hour and 6–8 hours after surgery. One patient with a history of elevation of serum creatinine had a minor increase of serum creatinine but had undetectable vancomycin levels. None of the other patients had a clinically significant increase in creatinine levels. Conclusions: Despite its relatively widespread usage, little data exist regarding the systemic levels and nephrotoxicity associated with the topical use of vancomycin powder in orthopaedic fracture surgery. These prospective data indicate that there seems to be little clinical concern regarding toxicity associated with systemic absorption of vancomycin powder in this specific clinical application. Level of Evidence: Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.

Intraoperative Tobramycin Powder Prevents Enterobacter cloacae Surgical Site Infections in a Rabbit Model of Internal Fixation Objectives: To evaluate the efficacy of intraoperative tobramycin powder in preventing surgical site infection (SSI) and implant colonization with Enterobacter cloacae in a rabbit fixation model. Gram-negative rods, particularly Enterobacter species, comprise an increasing percentage of SSI at our institution. Methods: Eighteen New Zealand White rabbits underwent surgical fixation of the left tibia with implantation of a plate and screws. The surgical site and implant were inoculated with 1 × 107 CFUs E. cloacae. The selected E. cloacae isolate was resistant to tobramycin and capable of forming biofilms. Nine rabbits received 125 mg tobramycin powder directly into the surgical site, overlying the implant. The control group was untreated. Fourteen days postinfection, the tibiae and implants were explanted. Radiographs were taken with and without the implants in place. One tibia from each group was examined after hematoxylin and eosin staining. The remaining tibiae and implants were morselized or sonicated, respectively, and plated on agar to determine infection burden. Data were analyzed with Fisher exact tests and Mann–Whitney U tests. Results: No bone infection or implant colonization occurred in the tobramycin-treated group. In the control group, 7 of 8 rabbits developed bone infections (P = 0.001), and 4 of 8 implants were colonized (P = 0.07). No gross disruption of the normal bone architecture was observed in either group. Conclusions: Intraoperative tobramycin powder applied at the time of contamination prevented bone infection with E. cloacae in this rabbit fixation model. The results are encouraging because the E. cloacae isolate was tobramycin-resistant, demonstrating the utility of intraoperative powdered antibiotics.

Comparison Between the Direct Anterior and Posterior Approaches for Total Hip Arthroplasty Performed for Femoral Neck Fracture Objectives: To compare 90-day and 1-year outcomes, including mortality, of femoral neck fracture patients undergoing total hip arthroplasty (THA) by direct anterior approach (DAA) versus posterior approach (PA). Design: Retrospective cohort. Setting: Level I Trauma Center. Patients: One hundred forty-three consecutive intracapsular femoral neck fractures treated with THA from 2010 to 2018. The minimum follow-up was 12 months, and the average follow-up was 14.6 months (12–72 months). Main Outcome Measures: Postoperative outcomes, including discharge ambulation, dislocation, periprosthetic joint infection, revision THA, and mortality at 90 days and 1 year after THA. Results: Of the 143 THA included, 44 (30.7%) were performed by DAA while 99 (69.3%) were performed by PA. In-hospital outcomes were similar between the cohorts. Compared with DAA patients, PA patients were more likely to ambulate without assistance preinjury (88.9% vs. 72.7%, P = 0.025) and be nonambulatory at the time of discharge (27.3% vs. 11.4%, P = 0.049). There were no significant differences in 90-day and 1-year postoperative outcomes between the DAA and PA groups, including dislocation, periprosthetic joint infection, periprosthetic fracture, mechanical complications, and revision surgery. Although there was no difference in mortality rate at 90 days, at 1-year follow-up the mortality rate was lower in the DAA group (0% vs. 11.1%, P = 0.018). Conclusions: Performing THA by DAA provides similar benefits in regards to medical and surgical outcomes compared with the PA for displaced femoral neck fracture. However, the DAA may lead to decreased 1-year mortality rates, possibly, because of improved early ambulation capacity that is an important predictor of long-term mortality. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Is Immediate Weight-Bearing Safe After Single Implant Fixation of Elderly Distal Femur Fractures? Objectives: To compare early complications in elderly patients with extra-articular distal femur fractures (DFFs) allowed to weight-bear as tolerated (WBAT) immediately versus patients prescribed initial touchdown weight-bearing (TDWB). Design: Retrospective cohort study. Setting: Level 1 academic trauma center. Patients: One hundred thirty-five patients 60 years or older who underwent surgical fixation of an extra-articular DFF, including the OTA/AO fracture classification of 33-A1-3, and periprosthetic fractures with a stable knee prosthesis (Lewis and Rorabeck type I or II) with at least 6 months follow-up. Intervention: Immediate WBAT or TDWB after surgical fixation of an extra-articular DFF with either an intramedullary nail or locked plate. Main Outcome Measurements: The primary outcome was a major adverse event within the first 6 months, defined as (1) early fixation failure or change in alignment leading to reoperation, (2) nonunion, or (3) deep infection. Secondary outcomes included postoperative inpatient length of stay, discharge disposition (secondary facility vs. home), malunion, mortality, and patient-reported outcomes. Results: The rate of early adverse events requiring reoperation was similar between the WBAT group (6, 10.7%) and the TDWB group (15, 19.0%; P = 0.23). There was no difference between groups with respect to length of stay, discharge disposition, malunion, and patient-reported outcomes. Conclusions: This study supports allowing carefully selected elderly patients, based on surgeon preference, to immediately weight-bear after operative fixation of an extra-articular DFF regardless of implant choice. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Organ Transplantation

Repeated kidney re-transplantation in times of organ shortage – a critical review Purpose of review Organ shortage forces those responsible to streamline allocation rules to provide a maximum of candidates with a graft and to optimize transplant outcome. Recently, repeated kidney re-transplantation was investigated in several studies with different analytic settings concerning the control group, the donors, parameters influencing outcome, and demographic characteristics. This review gives an overview on the candidates awaiting a repeated re-transplantation, summarizes the outcome, and comments on the relevance of these findings in the context of sustained organ shortage. Recent findings Repeated kidney re-transplantation is technically and immunologically feasible and the recipients' survival is better compared to candidates remaining on dialysis or on the waiting-list. However, the outcome is mainly reported to be worse as compared to first or second kidney transplantation. Kidneys from living donors seem to have a favorable impact on outcome in this setting. Summary The survival benefit of repeated re-transplantation recipients over patients on dialysis demands for continuation of this procedure. Comprehensive registries are essential to continuously optimize allocation. Governmental authorities are obliged to set the course to increase organ donation rather than forcing transplant decision makers to withhold a third or fourth graft from any candidate. Correspondence to Volker Assfalg, TransplanTUM, Munich Transplant Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Surgery, Ismaningerstr. 22, D-81675 Munich, Germany. Tel: +49 (0) 89 4140 2121; fax: +49 (0) 89 4140 4870; e-mail: volker.assfalg@tum.de Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Developments in immunosuppression Purpose of review In this review, we discuss achievements in immunosuppression in kidney transplant recipients published at last 18 months. Recent findings Results of recent trials with everolimus in low-risk primary kidney transplant recipients suggest that lowTAC/EVR combination is noninferior and CMV and BKV viral infections are less frequent to standTAC/MPA. Iscalimab monoclonal antibody, which prevents CD40 to CD154 binding, has just recently entered phase II clinical studies in kidney transplantation. Eculizumab, anti-C5 monoclonal antobody was recently shown to improve outcomes in DSA+ living-donor kidney transplant recipients requiring pretransplant desensitization because of crossmatch positivity. Proximal complement C1 inhibition in patients with antibody-mediated rejection was studied in several phase I trials. Summary Recent knowledge creates a path towards future immunosuppression success in sensitized recipients and in those in high risk of viral infections or CNI nephrotoxicity. Correspondence to Ondrej Viklicky, MD, PhD, Professor of Medicine, Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague, Czech Republic. Tel: + 420 23605 4110; fax: +420 23605 3168; e-mail: ondrej.viklicky@ikem.cz Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Kidney and pancreas transplant candidacy Purpose of review Kidney and/or pancreas transplantation candidacy criteria have evolved significantly over time reflecting improved pre and post-transplant management. With improvement in medical care, potential candidates for transplant not only are older but also have complex medical issues. This review focuses on the latest trends regarding candidacy for kidney and/or pancreas transplantation along with advances in pretransplant cardiac testing. Recent findings More candidates are now eligible for kidney and/or pancreas transplantation owing to less stringent candidacy criteria especially in regards to age, obesity, frailty and history of prior malignancy. Pretransplant cardiovascular assessment has also come a long way with a focus on less invasive strategies to assess for coronary artery disease. Summary Criteria for kidney and/or pancreas transplantation are expanding. Patients who in the past might have been declined because of numerous factors are now finding that transplant centers are more open minded to their candidacy, which could lead to better access to organ transplant wait list. Correspondence to Rafael Villicana, MD, Transplant Institute, Loma Linda University Health, 197 East, Caroline Street Suite 1400, San Bernardino, CA 92408, USA. Tel: +1 909 558 3144; e-mail: rvillicana@llu.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

New concepts in chronic antibody-mediated kidney allograft rejection: prevention and treatment Purpose of review Chronic antibody-mediated rejection (AMR) is a cardinal cause of transplant failure, with currently no proven effective prevention or treatment. The present review will focus on new therapeutic concepts currently under clinical evaluation. Recent findings One interesting treatment approach may be interference with interleukin-6 (IL-6) signaling to modulate B-cell immunity and donor-specific antibody (DSA) production. Currently, a large phase III randomized controlled trial is underway to clarify the safety and efficacy of clazakizumab, a high-affinity anti-IL-6 antibody, in chronic AMR. A prevention/treatment strategy may be costimulation blockade using belatacept to interfere with germinal center responses and DSA formation. In a recent uncontrolled study, belatacept conversion was shown to stabilize renal function and dampen AMR activity. Moreover, preliminary clinical results suggest efficacy of CD38 antibodies to deplete plasma and natural killer cells to treat AMR, with anecdotal reports demonstrating at least transient resolution of active rejection. Summary There are promising concepts on the horizon for the prevention and treatment of chronic AMR. The design of adequately powered placebo-controlled trials to clarify the safety and efficacy of such new therapies, however, remains a big challenge, and will rely on the definition of precise surrogate endpoints predicting long-term allograft survival. Mapping the natural history of AMR would greatly help the understanding of who would derive benefits from treatment. Correspondence to Georg A. Böhmig, MD, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Tel: +43 1 40400 43630; fax: +43 1 40400 39302; e-mail: georg.boehmig@meduniwien.ac.at Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Variations in DNA methylation and allograft rejection Purpose of review DNA methylation is involved in gene transcription and as such important for cellular function. Here, the literature on DNA methylation in relation to acute rejection is summarized with a focus on the potential clinical utility of DNA methylation for monitoring transplant rejection. Recent findings The tight transcriptional control of DNA methylation in immune cell function, e.g. demethylation in regulatory T-cell-specific genes for stable immunosuppressive capacities, suggests an important role for DNA methylation variations in the antidonor-directed immune response. Until today, differentially methylated DNA in immune cells, however, has not been described at the moment of allograft rejection. The ability to locus-specific modify DNA methylation could facilitate the generation of stable cells for cellular therapy purposes. The unique cell-specific characteristics of DNA methylation provide the opportunity to identify its cellular origin. Examining methylation of cell-free DNA in blood or urine may serve as a 'liquid biopsy' enabling minimally invasive detection of allograft rejection. Summary Actual research publications on DNA methylation in relation to allograft rejection are scarce, which makes it challenging to determine its potential clinical value. Extensive research is needed to investigate the value of DNA methylation in early recognition, diagnosis, and/or successful treatment of allograft rejection. Correspondence to Karin Boer, PhD, Erasmus MC, Room Na-520, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel: +3110 7035419; e-mail: karin.boer@erasmusmc.nl Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Cardiac evaluation of the kidney or liver transplant candidate Purpose of review As the field of transplant has advanced, cardiac events have become the leading cause of morbidity and mortality after liver and kidney transplantation ahead of graft failure and infection. This trend has been bolstered by the transplantation of older and sicker patients who have a higher burden of cardiovascular risk factors, accentuating the need to determine which patients should undergo more extensive cardiac evaluation prior to transplantation. Recent findings Computed tomography coronary angiography with or without coronary artery calcium scoring is now preferred over stress imaging in most transplant candidates for assessment of coronary artery disease. Assessment of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended, particularly in liver transplant candidates who are at high risk of cirrhotic cardiomyopathy, for which new diagnostic criteria were recently published in 2019. Summary Cardiac evaluation of liver and kidney transplant candidates requires a global assessment for both short and long-term risk for cardiac events. Imaging of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended. Risk stratification should consider both the anatomic and functional consequences of coronary artery disease in transplant candidates. Video abstract http://links.lww.com/MOT/A27 Correspondence to Lisa B. VanWagner, MD, MSc, FAST, FAHA, Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St Clair St - Suite 1400, Chicago, IL 60611, USA. Tel: +1 630 695 1632; fax: +1 312 695 3999; e-mail: lvw@northwestern.edu Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-transplantation.com). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Epigenetic modifications and the development of kidney graft fibrosis Purpose of review To outline recent discoveries in epigenetic regulatory mechanisms that have potential implications in the development of renal fibrosis following kidney transplantation. Recent findings The characterization of renal fibrosis following kidney transplantation has shown TGFβ/Smad signaling to play a major role in the progression to chronic allograft dysfunction. The onset of unregulated proinflammatory pathways are only exacerbated by the decline in regulatory mechanisms lost with progressive patient age and comorbidities such as hypertension and diabetes. However, significant developments in the recognition of epigenetic regulatory markers upstream of aberrant TGFβ-signaling has significant clinical potential to provide therapeutic targets for the treatment of renal fibrosis. In addition, discoveries in extracellular vesicles and the characterization of their cargo has laid new framework for the potential to evaluate patient outcomes independent of invasive biopsies. Summary The current review summarizes the main findings in epigenetic machinery specific to the development of renal fibrosis and highlights therapeutic options that have significant potential to translate into clinical practice. Correspondence to Valeria R. Mas, MS, PhD, FAST, Professor of Surgery, Chief, Surgical Sciences Division, Department of Surgery, School of Medicine, University of Maryland, HSF3 Building, W Baltimore Street, 7th Floor, Room 71, Baltimore, MD 21201, USA. Tel: +1 901 448 3071; fax: +1 901 448 3071; e-mail: vmas@som.umaryland.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Technical advancements in epigenomics and applications in transplantation Purpose of review To summarize recently developed next generation sequencing-based methods to study epigenomics and epitranscriptomics. To elucidate the potential applications of these recently developed methods in transplantation research. Recent findings There are several methods established with the collaborative efforts from different consortiums, such as ENCODE, Human Cell Atlas, and exRNA consortium to study role of epigenetics in human health. Rapid development in the sequencing technology also enabled the establishment of these genome-wide studies. This review specifically focuses on these techniques, such as EM-seq to study DNA methylation, CUT&RUN, and CUT&Tag to study histone/transcription factor--DNA interactions, ATAC-seq to study chromatin accessibility, Hi-C to explore 3D genome architecture and several methods to study epigenetics at single-cell level. In addition, we briefly mentioned recent efforts to study lncRNAs and extracellular miRNAs. Summary Technical advancements in genomics, particularly epigenomics, shed light on the role of epigenetics and recently epitranscriptomics in different fields. Application of those techniques to transplantation research is still very limited because of technical limitations. On the other hand, there are a lot of promising studies showing that these new techniques can be adapted to study the molecular biology of transplant-related problems. Correspondence to Canan Kuscu, PhD, Transplant Research Institute, University of Tennessee Health Science Center, 71S Manassas Street, TSRB Rm 421, Memphis, TN 38103, USA. Tel: +1 901 448 3162; e-mail: ckuscu@uthsc.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Systems biology approaches in solid organ transplantation Purpose of review Organ transplantation research has led to the discovery of several interesting individual mechanistic pathways, molecules and potential drug targets but there are still no comprehensive studies that have addressed how these varied mechanisms work in unison to regulate the posttransplant immune response that drives kidney rejection and dysfunction. Recent findings Systems biology is a rapidly expanding field that aims to integrate existing knowledge of molecular concepts and large-scale genomic and clinical datasets into networks that can be used in cutting edge computational models to define disease mechanisms in a holistic manner. Systems biology approaches have brought a paradigm shift from a reductionist view of biology to a wider agnostic assessment of disease from several lines of evidence. Although the complex nature of the posttransplant immune response makes it difficult to pinpoint mechanisms, systems biology is enabling discovery of unknown biological interactions using the cumulative power of genomic data sets, clinical data and endpoints, and improved computational methods for the systematic deconvolution of this response. Summary An integrative systems biology approach that leverages genomic data from varied technologies, such as DNA sequencing, copy number variation, RNA sequencing, and methylation profiles along with long-term clinical follow-up data has the potential to define a framework that can be mined to provide novel insights for developing therapeutic interventions in organ transplantation. Correspondence to Sunil M. Kurian, PhD, Research Scientist, Scripps Clinic Bio-Repository & Bio-Informatics Core, Scripps Center for Organ & Cell Transplantation Research, 10666 N. Torrey Pines Road, 200N, La Jolla, CA 92037, USA. Tel: +1 858 554 4371; e-mail: Kurian.Sunil@scrippshealth.org Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing Purpose of review Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant biomedical literature. Recent findings Sequencing is a technique to determine the order of nucleotides in a segment of RNA or DNA. RNA-seq of kidney allograft tissues has revealed novel mechanistic insights but does not provide information on individual cell types and cell states. scRNA-seq enables to study the transcriptome of individual cells and assess the transcriptional differences and similarities within a population of cells. Initial studies on rejecting kidney allograft tissues in humans have identified the transcriptional profile of the active players of the innate and adaptive immune system. Application of scRNA-seq in a preclinical model of kidney transplantation has revealed that allograft-infiltrating myeloid cells follow a trajectory of differentiation from monocytes to proinflammatory macrophages and exhibit distinct interactions with kidney allograft parenchymal cells; myeloid cell expression of Axl played a major role in promoting intragraft myeloid cell and T-cell differentiation. Summary The current review discusses the technical aspects of scRNA-seq and summarizes the application of this technology to dissect the human kidney allograft transcriptome. Correspondence to Thangamani Muthukumar, MD, Division of Nephrology, Hypertension, and Transplantation Medicine, Weill Cornell Medicine, 525 E 68 Street, Box 3, New York, NY 10065, USA. Tel: +1 212 746 4430; fax: +1 212 746 6894; e-mail: mut9002@med.cornell.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Pulmonary Medicine

Beta-blockers in chronic obstructive pulmonary disease: the good, the bad and the ugly Purpose of review Several observational studies have suggested that β-blockers, especially cardioselective ones, are well tolerated and associated with a lower risk of acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD). However, there are dissenting studies. This review provides an update on the use of β-blockers in COPD, focusing on results of recent prospective studies and randomized controlled trials. Recent findings In totality, cohort studies indicate that β-blockers are generally well tolerated and effective in COPD patients who also have a clear cardiovascular indication for these groups. Although β-blockers on average reduce lung function acutely in COPD patients, the absolute decrease is relatively small, especially if cardioselective β-blockers are used. The results of two large randomized controlled trials suggest that concomitant β-blocker use does not reduce the therapeutic benefits of inhaled bronchodilators in COPD patients. The use of β-blockers in COPD patients, who do not have overt cardiovascular disease, does not prevent COPD exacerbations and may paradoxically increase the risk of COPD-related hospitalization and mortality. Summary The use of β-blockers is generally well tolerated and effective in COPD patients, who also have a clear cardiovascular indication for these drugs. However, they should not be used in patients who do not have overt cardiovascular disease as β-blockers can reduce lung function, worsen health status and increase the risk of COPD-related hospitalization. Correspondence to Don D. Sin, Tier 1 Canada Research Chair in COPD, de Lazzari Family Chair at the UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada V6Z 1Y6. Tel: +1 604 806 8346; fax: +1 604 806 9274; e-mail: don.sin@hli.ubc.ca Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

ICU preparedness in pandemics: lessons learned from the coronavirus disease-2019 outbreak Purpose of review The worldwide SARS-CoV-2 pandemic has taken a heavy toll on ICUs worldwide. This review expounds on lessons learned for ICU preparedness during the pandemic and for future mass casualty events. Recent findings In the 21st century, there have already been several outbreaks of infectious diseases that have led to mass casualties creating ICU strain, providing multiple opportunities for hospitals and hospital systems to prepare their ICUs for future events. Unfortunately, the sheer scale and rapidity of the SARS-CoV-2 pandemic led to overwhelming strain on every aspect of ICU disaster preparedness. Yet, by analyzing experiences of hospitals throughout the first 7 months of the current pandemic in the areas of infection control, equipment preparedness, staffing strategies, ICU spatial logistics as well as acute and postacute treatment, various important lessons have already emerged that will prove critical for successful future ICU preparedness. Summary Preemptive planning, beginning with the early identification of staffing resources, supply chains and alternative equipment sources, coupled with strong infection control practices that also provide for the flexibility for evolving evidence is of utmost importance. However, there is no single approach that can be applied to every health system. Correspondence to Amesh Adalja, MD, Johns Hopkins Center for Health Security, 621 East Pratt Street, Suite 210, Baltimore, MD 21202, USA. Tel: +1 443 573 3304; e-mail: aadalja1@jhu.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Diagnostic and therapeutic challenges of chronic obstructive pulmonary disease in the elderly Purpose of review Chronic obstructive pulmonary disease (COPD) imposes a large burden on the global population and even more so for the elderly who face significant obstacles in the diagnosis, management, and psychosocial effects of the disease. This review describes the current challenges and key points in the management of COPD in the elderly. Recent findings Lower limit rather than fixed cut off of the FEV1/FVC ratio can improve the diagnosis and better predict COPD mortality. High relative to standard dose influenza vaccination reduces confirmed cases of influenza overall and reduces hospitalizations in older nursing home residents. Simple interventions that include electronic health record tracking can significantly improve vaccination rates. Although many inhaler and nebulized medications are available for the elderly, the final regimen is usually determined by a combination of expense, issues with proper device use (from difficulty with coordination, hand grip, inspiratory flows or cognitive function) and the side effect profile. Fortunately, the switch to cheaper or better covered alternatives can be well tolerated with improvement in adherence and exacerbations of COPD. Finally, caution should be made against ageism, which may be a factor in the recommendation of rehabilitation or palliative care in the elderly COPD patient, as both are underused despite evidence of benefit. Summary Although care for the elderly COPD patient can be difficult, we summarize key points that the physician should be cognizant of to provide comprehensive care. Correspondence to Loutfi S. Aboussouan, MD, Cleveland Clinic, Respiratory Institute, A90, 9500 Euclid Ave, Cleveland, OH 44195, USA. Tel: +1 216 444 0420; fax: +1 216 445 8160; e-mail: aboussl@ccf.org Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Lipidology

Impact drugs targeting cardiometabolic risk on the gut microbiota Purpose of review Alterations in the gut microbiome composition or function are associated with risk factors for cardiometabolic diseases, including hypertension, hyperlipidemia and hyperglycemia. Based on recent evidence that also oral medications used to treat these conditions could alter the gut microbiome composition and function and, vice versa, that the gut microbiome could affect the efficacy of these treatments, we reviewed the literature on these observed interactions. Recent findings While the interaction of metformin with the gut microbiome has been studied most, other drugs that target cardiometabolic risk are gaining attention and often showed associations with alterations in microbiome-related features, including alterations in specific microbial taxa or pathways, microbiome composition or microbiome-derived metabolites, while the gut microbiome was also involved in drug metabolism and drug efficacy. As for metformin, for some of them even a potential therapeutic effect via the gut microbiome is postulated. However, exact mechanisms remain to be elucidated. Summary There is growing interest in clarifying the interactions between the gut microbiome and drugs to treat hypertension, hyperlipidemia and hyperglycemia as well as the first pass effect of microbiome on drug efficacy. While mostly analysed in animal models, also human studies are gaining more and more traction. Improving the understanding of the gut microbiome drug interaction can provide clinical directions for therapy by optimizing drug efficacy or providing new targets for drug development. Correspondence to Max Nieuwdorp, MD, PhD, Department of Internal and Vascular Medicine, Amsterdam Diabetes Center, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, Room D3-211, 1105 AZ Amsterdam, The Netherlands. E-mail: m.nieuwdorp@amsterdamumc.nl Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Impact of ultra-processed food consumption on metabolic health Purpose of review Ultra-processed foods (UPF) have been associated with poor diet quality and adverse health outcomes. Our aim in this review is to summarize recent research assessing the impact of UPF consumption, classified according to the NOVA system, on outcomes related to metabolic health. Recent findings Thirty recent studies with different design, quality and target population have investigated the impact of UPF consumption on parameters related to metabolic health, which were organized into: metabolic syndrome; body weight change and obesity indicators; blood pressure and hypertension; glucose profile, insulin resistance and type 2 diabetes; other metabolic risks and cardiovascular diseases and mortality. Most of the studies demonstrated adverse associations between high UPF consumption and metabolic health, mainly those with robust design and involving adults. Summary Most of the latest findings have revealed an adverse impact of high UPF consumption on metabolic health, including cardiovascular diseases and mortality. Scientific evidence is accumulating towards the necessity of curbing UPF consumption worldwide at different life stages. Nevertheless, other studies are needed to confirm the causality between UPF consumption and metabolic health in diverse scenarios and to better elucidate all likely mechanisms involved in this relationship. Correspondence to Renata Bertazzi Levy, Department of Preventive Medicine, School of Medicine, University of São Paulo, 455 Dr Arnaldo Avenue, 2nd floor, 01246-903 São Paulo-SP, Brazil. Tel: +55 11 3061 8608; e-mail: rlevy@usp.br Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The COVID-19 pandemic: lifestyle and cardiovascular risk factors No abstract available

Deep dive to the secrets of the PREDIMED trial Purpose of review The aim of this study was to briefly summarize the contribution of the PREDIMED (PREvención con DIeta MEDiterránea) trial on cardiovascular evidence and examine in depth its groundbreaking trajectory. PREDIMED was conducted during 2003–2010 and represented the largest primary prevention trial ever testing the effects of changes in a complete food pattern (namely, the Mediterranean diet) on cardiovascular disease (CVD). Major contributions relied on the relevant changes in the food pattern attained by the behavioural intervention and their robust effect in reducing hard clinical end-points. Given some potential concerns, which were appropriately addressed with supporting analyses, this review is timely and relevant. Recent findings PREDIMED has continued contributing to the existing literature with extensive, robust and abundant new evidence on the benefits of the Mediterranean diet, particularly on cardiovascular health, including recent studies using high-throughput metabolomic techniques. After robustly addressing some controversies, the conclusions of the original trial remained unaltered. Summary The Mediterranean diet represents an effective and robust nutritional strategy against CVD in high cardiovascular risk populations. Recent findings from the PREDIMED have identified a metabolic signature of the Mediterranean diet that can objectively determine dietary adherence and predict CVD risk. This metabolomic signature opens up a new era for nutritional epidemiology and personalized nutrition. Correspondence to Miguel Ruiz-Canela, Department of Preventive Medicine and Public Health, Facultad de Medicina, Irunlarrea 1, 31008 Pamplona, Spain. Tel: +34 948 42 56 00 x806395; fax: +34 948 425 740; e-mail: mcanela@unav.es Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The role of the molecular circadian clock in human energy homeostasis Purpose of review The aim of this review is to present the latest findings on the role of the circadian clock in the control of metabolism, and the therapeutic potential of chronotherapy to regulate energy homeostasis in humans. Recent findings We summarized the recent advances related to circadian clock regulation of food intake and energy expenditure. In peripheral organs, mitochondrial oxidative capacity and lipolysis show circadian pattern in humans, and rhythms disruption may be involved in the pathogenesis of metabolic diseases. Indeed, circadian desynchrony affects food intake, insulin sensitivity, and increases the risk of developing metabolic disease. Time-targeted strategies, which aim to synchronize external cues with the molecular clock to improve metabolic outcomes, have positive effects on metabolism in humans, with several studies showing that time-targeted feeding improves body weight loss and glucose tolerance. Summary The interest in time-targeted strategies to prevent or manage metabolic disturbances has grown this past year with encouraging health benefits. To maximize the therapeutic effect of these strategies, further research is warranted to delineate the molecular regulation of metabolic processes controlled by the clock and especially its modulation in contexts such as aging, sex differences, or metabolic diseases. Correspondence to Juleen R. Zierath, Department of Molecular Medicine and Surgery, Section of Integrative Physiology, Biomedicum, Solnavägen 9, SE-171 77 Stockholm, Sweden. E-mail: Juleen.zierath@ki.se Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Mendelian randomization as a tool for causal inference in human nutrition and metabolism Purpose of review The current review describes the fundamentals of the Mendelian randomization framework and its current application for causal inference in human nutrition and metabolism. Recent findings In the Mendelian randomization framework, genetic variants that are strongly associated with the potential risk factor are used as instrumental variables to determine whether the risk factor is a cause of the disease. Mendelian randomization studies are less susceptible to confounding and reverse causality compared with traditional observational studies. The Mendelian randomization study design has been increasingly used in recent years to appraise the causal associations of various nutritional factors, such as milk and alcohol intake, circulating levels of micronutrients and metabolites, and obesity with risk of different health outcomes. Mendelian randomization studies have confirmed some but challenged other nutrition-disease associations recognized by traditional observational studies. Yet, the causal role of many nutritional factors and intermediate metabolic changes for health and disease remains unresolved. Summary Mendelian randomization can be used as a tool to improve causal inference in observational studies assessing the role of nutritional factors and metabolites in health and disease. There is a need for more large-scale genome-wide association studies to identify more genetic variants for nutritional factors that can be utilized for Mendelian randomization analyses. Correspondence to Susanna C. Larsson, PhD, Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. E-mail: susanna.larsson@surgsci.uu.se Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Impact of metabolic dysfunction on cognition in humans Purpose of review The current review evaluates the recent literature on the impact of metabolic dysfunction in human cognition, focusing on epidemiological studies and meta-analyses of these. Recent findings Worldwide around 50 million people live with dementia, a number projected to triple by 2050. Recent reports from the Lancet Commission suggest that 40% of dementia cases may be preventable primarily by focusing on well established metabolic dysfunction components and cardiovascular risk factors. Summary There is robust evidence that type 2 diabetes and midlife hypertension increase risk of dementia in late life. Obesity and elevated levels of LDL cholesterol in midlife probably increase risk of dementia, but further research is needed in these areas. Physical activity, diet, alcohol, and smoking might also influence the risk of dementia through their effect on metabolic dysfunction. A key recommendation is to be ambitious about prevention, focusing on interventions to promote healthier lifestyles combating metabolic dysfunction. Only comprehensive multidomain and staff-requiring interventions are however efficient to maintain or improve cognition in at-risk individuals and will be unrealistic economic burdens for most societies to implement. Therefore, a risk score that identifies high-risk individuals will enable a targeted early intensive intervention toward those high-risk individuals that will benefit the most from a prevention against cardiovascular risk factors and metabolic dysfunction. Correspondence to Ruth Frikke-Schmidt, Professor, MD, DMSc, PhD, Chief Physician, Department of Clinical Biochemistry KB 3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Tel: +45 3545 4348; fax: +45 3545 2880; e-mail: ruth.frikke-schmidt@regionh.dk Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Liver fat storage pathways: methodologies and dietary effects Purpose of review Nonalcoholic fatty liver is the result of an imbalance between lipid storage [from meal, de novo lipogenesis (DNL) and fatty acid (FA) uptake] and disposal (oxidation and VLDL output). Knowledge on the contribution of each of these pathways to liver fat content in humans is essential to develop tailored strategies to prevent and treat nonalcoholic fatty liver. Here, we review the techniques available to study the different storage pathways and review dietary modulation of these pathways. Recent findings The type of carbohydrate and fat could be of importance in modulating DNL, as complex carbohydrates and omega-3 FAs have been shown to reduce DNL. No effects were found on the other pathways, however studies investigating this are scarce. Summary Techniques used to assess storage pathways are predominantly stable isotope techniques, which require specific expertise and are costly. Validated biomarkers are often lacking. These methodological limitations also translate into a limited number of studies investigating to what extent storage pathways can be modulated by diet. Further research is needed to elucidate in more detail the impact that fat and carbohydrate type can have on liver fat storage pathways and content. Correspondence to Patrick Schrauwen, Department of Nutrition and Movement Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. Tel: +31 43 388 15 02; e-mail: p.schrauwen@maastrichtuniversity.nl This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Psychiatry

Antipsychotic Prescriptions for Patients with Dementia: The Strengths and Weaknesses of the National Health Insurance System of Taiwan Tzung- Jeng Hwang, Helen F K. Chiu, Te- Jen Lai Taiwanese Journal of Psychiatry 2020 34(4):149-151

A History of Antidementic Drug Development in Japan Masatoshi Takeda, Shinji Tagami Taiwanese Journal of Psychiatry 2020 34(4):152-161 Objective: Japan is the top runner in the world in society aging, in which the number of patients with Alzheimer's disease has significantly increased and still keeps increasing. Many countries and societies are still struggling with people with dementia and the burden related to the high number of the elderly. In this study, both authors have been involved with research works on elucidating the pathological process of Alzheimer's disease and developing antidementic drugs for more than 30 years. Methods: Based on lifetime professional experiences in basic research and clinical work as well as our own contribution in the areas of expertise, we describe in this review the changes of the number of dementia patients and the concept of dementia, as well as the development of antidementic drugs in Japan. Results: In this review, we define the super-aged society first. Historical concept changes in Alzheimer's disease, perspectives of research on Alzheimer's disease and drug development, history of antidementic drug developments (for nootropics and drugs for improving brain metabolism and circulation, development of symptom-modifying drugs; hormones, neurotrophic factors, etc.; acetylcholinergic drugs; and glutamatergic drugs), and development of disease-modifying drugs (with amyloid cascade hypothesis, nonsteroidal anti-inflammatory drugs, and amyloid vaccine) have been outlined as review sections. Finally, we devote discussion in two review sections – failure of new drugs and development from the existing drugs as well as development of preemptive medicine. Conclusion: We hope that the whole society, including the elderly with and without cognitive decline, can resolve this issue in the near future.

Suicidal Ideation, Quality of Life, and Psychometric Outcomes in Taiwanese Military Personnel with Subjective Hypersomnia or Insomnia Chu-Wei Tsai, Yueh-Ming Tai, Szu-Nian Yang Taiwanese Journal of Psychiatry 2020 34(4):162-167 Background: To clarify the symptom discrepancies in suicidality, psychiatry outcomes, and quality of life (QOL), we did a cross-sectional study recruiting military personnel with hypersomnia or insomnia in three camps in northern Taiwan. Methods: With consents of volunteer audience attending a one-hour mental health education program, all qualified active service military personnel were asked to fill out copies of questionnaire describing their current situation. Results: About one-fourth of the 135 samples admitted their current condition of subjective feelings of insomnia (28.15%) or hypersomnia (24.44%), but < 15% of them had ever asked health providers for psychological or clinical help. Compared with controls without any sleep problem, individuals with suicidal ideation in the other two groups were more prevalent, with higher anxiety, depression, and significantly lower total score of QOL (p < 0.05). The insomnia group was significantly unsatisfied with their sleep the most (p < 0.001). The hypersomnia group showed significantly higher mean scores of irritability (p < 0.001). Those findings were more vigorous and predominate even adjusting for confounding effects of age and sex. Conclusion: This study revealed a different prevalence and adversity between subjective insomnia and hypersomnia groups among military population. Further relevant evaluation and management are warranted.

Validation of Brain Health Test-7 for Detecting Patients with Mild Cognitive Impairment and Early Dementia Mei- Xian Loi, Hsi- Chung Chen, Ming- Hsien Hsieh, Yi- Ting Lin, Chen- Chung Liu, Pei- Ning Wang, Chih- Cheng Hsu, Tzung- Jeng Hwang Taiwanese Journal of Psychiatry 2020 34(4):168-173 Objectives: We intended to develop a simple dementia screening tool to help primary care physicians identify patients with mild cognitive impairment (MCI) and early dementia. Methods: The brain health test-7 (BHT-7) was developed based on the original BHT study. Study patients aged 50 years and above with normal cognition, MCI, and dementia were recruited. All patients received evaluation with the BHT-7, mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), and clinical dementia rating (CDR) for cognitive function. The performance of BHT-7 in identifying cognitive impairment was compared with that of MMSE and MoCA. Results: We enrolled 376 study participants. The mean BHT-7, MMSE, and MoCA scores showed significant differences among the three groups. Compared to MMSE and MoCA, the BHT-7 (sensitivity = 86%, specificity = 76%, area under curve = 88%) showed better sensitivity in differentiating MCI from the normal group, with a cutoff value of 17/18. The scores of the three tests were all affected by educational level. Conclusion: The BHT-7 is a simple and easy-to-use cognitive screening tool that may be useful in primary care settings to identify patients with MCI or early dementia.

The Impact of Sex Differences and Oral Health Behaviors on Oral Health-related Quality of Life among Patients with Schizophrenia in Taiwan: A Cross-sectional Study Li- Ling Huang, Kuan- Ying Hsieh, Shu- Wen Chen, Shu- Fen Yu, Shu- Mei Chang, Shu- Yun Chen, Frank Huang-Chih Chou Taiwanese Journal of Psychiatry 2020 34(4):174-180 Objective: Oral health denotes general well-being, meaning that the person can perform functions such as eating, talking, and keeping smile. Those functions can impact on oral health-related quality of life (OHRQoL) with differences between sexes. In this study, we intended to examine sex differences and oral health behaviors in OHRQoL among institutionalized patients with schizophrenia. Methods: We recruited 150 institutionalized patients (99 men and 51 women) with schizophrenia in a nursing home. We measured OHRQoL with the 36-item Short-form Health Survey (SF-36) questionnaire, and oral health by oral cleaning habits, oral health problems, and oral health care. Results: The mean values of the SF-36 physical component summary (PCS) score and mental component summary (MCS) score were 62.4 and 49.9, respectively, which were lower in women than those in men. Cooperativeness was a protective factor, but toothache and bleeding gums were risk factors in PCS. The standard cleaning method and cooperativeness were protective factors, but toothache, bleeding gums, and swollen gums were risk factors in MCS. Conclusion: Our study finding showed that women tended to report poorer physical and OHRQoL than men even after controlling oral health behaviors and problems. Toothache and bleeding gums were risk factors for poor OHRQoL. The findings provide useful information for health-care resource planning in patients with schizophrenia.

Correlates Related to Probable Common Mental Disorders among Ketamine Users: Cognitive and Urinary Impairments Chih- Jen Wang, Li- Ling Huang, Yu- San Chang, Ching- Hong Tsai, Yu- Hsuan Wu, Yi- Fan Lin, Wen- Huei Lin, Kuan- Ying Hsieh Taiwanese Journal of Psychiatry 2020 34(4):181-187 Objective: In this study, we intended to determine the prevalence of common mental disorder (probable CMD) in ketamine users in Taiwan and identify whether factors including cognitive and urinary impairments developed over the course of ketamine use were correlated with probable CMD. Methods: Through a cross-sectional study design, 538 participants (115 women and 423 men) were recruited from reformatory educational classes in Taiwan. We used the 12-item Chinese Health Questionnaire to evaluate probable CMD. Furthermore, we designed a copy of questionnaire regarding ketamine use including questions related to age at first contact with ketamine, ketamine use expenses per month, intervals of use, route, concomitant substance use, legal problems, as well as cognitive and urinary impairments developed over the course of ketamine use. The relationships between ketamine use, physical health, concomitant substance use, cognitive impairments, urinary impairments, and probable CMD were examined using logistic regression analysis. Results: In this study, the prevalence of probable CMD among ketamine users in Taiwan was 19.7%. We found that poor physical health (from p < 0.05 to p < 0.001 for all kinds of severity), comorbid sedatives or hypnotic use (p < 0.01), and moderate cognitive impairments (p < 0.05) significantly developed after ketamine use were all independent factors correlated with probable CMD. But urinary impairments developed after ketamine use did not show any significant difference in regression analysis when considering other confounding factors. Conclusion: We suggest that an early survey of physical health, concomitant use of sedatives or hypnotics, and cognitive impairment can detect mental health problems among ketamine users.

The Validity of Inventory of Depressive Symptomatology, Self-report and the Association of Depression with Professional Help-seeking among Individuals with Social Anxiety Disorder Jian- Ting Chen, Yi- Ting Lin, Huai- Hsuan Tseng, An- Sheng Lin, Hsi- Chung Chen, Ya- Mei Bai, Chao- Cheng Lin Taiwanese Journal of Psychiatry 2020 34(4):188-195 Objectives: Patients with social anxiety disorder (SAD) often have a fear of seeking professional help. In this study, we intended to validate the Taiwanese version of the Inventory of Depressive Symptomatology, Self-report (IDS-SR), and to investigate whether severity of depression and/or social anxiety is associated with professional help-seeking among Internet users with SAD. Methods: In the study part I, we recruited volunteers through the internet, assessed their social anxiety and depression, and examined the Taiwanese version of the IDS-SR. In study Part II, we again recruited volunteers from the Internet and outpatient clinic, and did the telephone or face-to-face interview to establish the validity of the IDS-SR. Finally, the results of both parts were integrated to analyze help-seeking behaviors. Results: We included 2,079 participants in study part I, which showed that the IDS-SR was reliable. In the Part II study, the IDS-SR was found to be valid from 104 participants. Among the study Part I participants who reached the threshold of SAD, a high prevalence (52.9%) of major depressive disorder was found. Multiple logistic regression analysis of scores of the participants who met the threshold of SAD (n = 1,483) revealed that the IDS-SR total score was significantly associated with professional help-seeking (p < 0.001), whereas the severity of social anxiety was not. Conclusion: The Taiwanese version of IDS-SR was valid and reliable. The severity of depression, rather than that of social anxiety, was associated with professional help-seeking behaviors among Internet users with SAD. Screening depression in people with SAD has the potential in identifying those who may seek professional help.

Therapeutic Factors in the Group Singing Therapy by Social Robot for Patients with Schizophrenia: A Pilot Study Yin- Huang Liao, Chia- Chun Wu, En- Lin Yang, Yi- Nuo Shih Taiwanese Journal of Psychiatry 2020 34(4):196-198 Objective: Fewer robots are being used for psychological care, the objective of this pilot study was to explore the therapeutic factors in the group singing therapy by social robot to interact with people with schizophrenia. Methods: In this pilot study, we recruited nine subjects who were aged between 28 and 62 years. They received four sections of group singing therapy given by asocial robot and an occupational therapist. Then, we collected a completed copy for therapeutic-factor questionnaire. Results: In this pilot study, the top three therapeutic factors in order were group cohesiveness, universality, and altruism. Conclusion: Social robot may be a good companion tool for chronic schizophrenia, and need to increase the number of subjects to improve the validity of the study results in the future.

Psychiatric Manifestations in a Patient with Both Huntington's Disease and Hyperthyroidism: A Case Report Yu- Tung Lee, Te- Jen Lai, Chun- Te Lee Taiwanese Journal of Psychiatry 2020 34(4):199-200

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