Visiting and Communication Policy in Intensive Care Units during COVID-19 Pandemic: A Cross-sectional Survey from South Asia and the Middle East.

Purpose: The coronavirus disease-2019 (COVID-19) pandemic had affected the visiting or communicating policies for family members. We surveyed the intensive care units (ICUs) in South Asia and the Middle East to assess the impact of the COVID-19 pandemic on visiting and communication policies. Materials and method: A web-based cross-sectional survey was used to collect data between March 22, 2021, and April 7, 2021, from healthcare professionals (HCP) working in COVID and non-COVID ICUs (one response per ICU). The topics of the questionnaire included current and pre-pandemic policies on visiting, communication, informed consent, and end-of-life care in ICUs. Results: A total of 292 ICUs (73% of COVID ICUs) from 18 countries were included in the final analysis. Most (92%) of ICUs restricted their visiting hours, and nearly one-third (32.3%) followed a "no-visitor" policy. There was a significant change in the daily visiting duration in COVID ICUs compared to the pre-pandemic times (p = 0.011). There was also a significant change (p <0.001) in the process of informed consent and end-of-life discussions during the ongoing pandemic compared to pre-pandemic times. Conclusion: Visiting and communication policies of the ICUs had significantly changed during the COVID-19 pandemic. Future studies are needed to understand the sociopsychological and medicolegal implications of revised policies. How to cite this article: Chanchalani G, Arora N, Nasa P, Sodhi K, Al Bahrani MJ, Al Tayar A, et al. Visiting and Communication Policy in Intensive Care Units during COVID-19 Pandemic: A Cross-sectional Survey from South Asia and the Middle East. Indian J Crit Care Med 2022;26(3):268-275.

Closing the Osteoporotic-Fracture Care Gap for Frail Older Persons.

Aim To implement standardised fracture risk assessment in the frail older person. Methods Frail older patients underwent opportunistic screening for fracture risk. Roadblocks to standardised assessment were identified. An Integrated Care Team for older persons (ICT) trained in fracture risk assessment using FRAX. Clinical assessment was via a locally agreed algorithm. Data was entered onto Excel. The SQUIRE guidelines for quality improvement programmes were used to report the results. Results Of 96 patients opportunistically screened, the average age was 84 years. FRAX was completed for 19% (n=18). 89% (n=16) met the pharmacotherapy threshold. Nine were recommended pharmacotherapy. Of sixteen patients recommended for DXA, just 31% (n=5) were booked. Following implementation of a quality improvement project, 100 patients were assessed, and average age was 80 years. FRAX was completed for 62% (n=63) and 95% (n=60) required pharmacotherapy. 24% (n=14) had untreated prior fracture. All had pharmacotherapy prescribed. 59% (n=59) required DXA scanning. 70% (n=41) had DXA ordered. Conclusion ICT ownership increased FRAX assessment 3-fold and point of contact prescribing to 100%.

Engineering of chimeric natural killer cell receptors to develop precision adoptive immunotherapies for cancer.

Natural killer (NK) cells are innate immune effectors which play a crucial role in recognizing and eliminating virally infected and cancerous cells. They effectively distinguish between healthy and distressed self through the integration of signals delivered by germline-encoded activating and inhibitory cell surface receptors. The frequent up-regulation of stress markers on genetically unstable cancer cells has prompted the development of novel immunotherapies that exploit such innate receptors. One prominent example entails the development of chimeric antigen receptors (CAR) that detect cell surface ligands bound by NK receptors, coupling this engagement to the delivery of tailored immune activating signals. Here, we review strategies to engineer CARs in which specificity is conferred by natural killer group 2D (NKG2D) or other NK receptor types. Multiple preclinical studies have demonstrated the remarkable ability of chimeric NK receptor-targeted T cells and NK cells to effectively and specifically eliminate cancer cells and to reject established tumour burdens. Importantly, such systems act not only acutely but, in some cases, they also incite immunological memory. Moreover, CARs targeted with the NKG2D ligand binding domain have also been shown to disrupt the tumour microenvironment, through the targeting of suppressive T regulatory cells, myeloid-derived suppressor cells and tumour vasculature. Collectively, these findings have led to the initiation of early-phase clinical trials evaluating both autologous and allogeneic NKG2D-targeted CAR T cells in the haematological and solid tumour settings.

Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma.

BACKGROUND: Death from pancreatic ductal adenocarcinoma (PDAC) is rising across the world and PDAC is predicted to be the second most common cause of cancer death in the USA by 2030. Development of effective biotherapies for PDAC are hampered by late presentation, a low number of differentially expressed molecular targets and a tumor-promoting microenvironment that forms both a physical, collagen-rich barrier and is also immunosuppressive. In 2017 Pancreatic Cancer UK awarded its first Grand Challenge Programme award to tackle this problem. The team plan to combine the use of novel CAR T cells with strategies to overcome the barriers presented by the tumor microenvironment. In advance of publication of those data this review seeks to highlight the key problems in effective CAR T cell therapy of PDAC and to describe pre-clinical and clinical progress in CAR T bio-therapeutics.

Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.

Implementation of National Institute for Health and Care Excellence (NICE) guidance to measure immunoglobulin A with all coeliac screens: can an affordable solution be devised?

There has been a dramatic increase in requests for coeliac disease (CD) serological screening using immunoglobulin (Ig)A tissue transglutaminase antibodies (IgA-tTG). Recently, the UK National Institute for Health and Care Excellence has revised its guidance, recommending that total IgA should also be measured in all samples. This is justified, as false-negative results may occur with IgA deficiency. However, implementation of this guidance will incur considerable expense. Tests that measure IgA-tTG antibodies can detect IgA deficiency, indicated by low background signal. This provides an opportunity to identify samples containing IgA ≤ 0·2g/l, obviating the need for unselected IgA measurement. We investigated the feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® enzyme-linked immunosorbent assay to quantify IgA-tTG antibodies. In both cases, total IgA correlated strongly with background IgA-tTG assay signal. Using the Celikey™ assay, a threshold of < 17·5 response units achieved 100% sensitivity (95% confidence intervals 79·4-100%) for detection of IgA ≤ 0·2g/l, circumventing the need for IgA testing in > 99% of sera. A similar principle was demonstrated for the QUANTA Lite® assay, whereby a threshold optical density of < 0·0265 also achieved 100% sensitivity (95% confidence intervals 78·2-100%) for IgA ≤ 0·2 g/l, avoiding unnecessary IgA testing in 67% of cases. These data suggest that CD screening tests can identify samples reliably containing low IgA in a real-life setting, obviating the need for blanket testing. However, this approach requires careful individualized validation, given the divergent efficiency with which assays identify samples containing low IgA.

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases.

Using routinely collected data to stratify prostate cancer patients into phases of care in the United Kingdom: implications for resource allocation and the cancer survivorship programme.

BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy in British men. The increasing use of PSA screening test has resulted in many more patients being diagnosed with this condition. Advances in its treatment have improved the survival rate among these patients. By 2040, the prevalence of prostate cancer survivors is expected to reach 830 000. Many of them will require medical support for the management of their progressive disease or long-term toxicities from previous treatments. Successful implementation of the cancer survivorship programme among these patients depends on a good understanding of their demand on the health care system. The aim of this study is to segment the population of prostate cancer survivors into different needs groups and to quantify them with respect to their phase of care. METHODS: Incidence, survival, prevalence and mortality data collected and reported by cancer registries across the United Kingdom have been used for the current study to provide indicative estimates as to the number of prostate cancer patients in each phase of the care pathway in a year. RESULTS: The majority of prostate cancer patients are in the post-treatment monitoring phase. Around a fifth of the patients are either receiving treatment or in the recovery and readjustment phase having completed their treatment in the preceding year. Thirteen percent have not received any anticancer treatment, a further 12% (32 000) have developed metastatic disease and 4% are in the final stage of their lives. CONCLUSION: On the basis of our estimates, patients undergoing post-treatment monitoring phase will constitute the biggest group among prostate cancer survivors. The pressure to provide adequate follow-up care to these patients will be a challenge. There is limited data available to definitively quantify the number of prostate cancer patients who follow different pathways of care, and we hope this study has highlighted the importance of collecting and reporting of such data to help future health care planning for these patients.

How should a district general hospital immunology service screen for anti-nuclear antibodies? An 'in-the-field' audit.

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISA(NEG) HEp-2(POS) ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen.

Wernicke's encephalopathy following hyperemesis gravidarum.

Wernicke's encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B1(thiamine) deficiency. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding. Most patients present with the triad of ocular signs, ataxia, and confusion. It can be associated with life-threatening complication like central pontine myelinolysis (CPM). We report two cases of WE following HG, with two different outcomes.

Implementing improved post-treatment care for cancer survivors in England, with reflections from Australia, Canada and the USA.

Increasing cancer incidence together with improved survival rates are contributing to the growing number of cancer survivors. Survivors may encounter a range of potential effects as a result of the cancer itself or cancer treatments. Traditionally, the major focus of follow-up care has been on detection of cancer recurrence; however, the efficacy of such strategies is questionable. Traditional follow-up frequently fails to identify or adequately address many survivors' concerns. Aftercare needs to be planned to enable better outcomes for survivors, while using scarce health-care resources efficiently. This review focuses on provision of survivorship care, rather than on research. England's National Cancer Survivorship Initiative has developed principles for improved care of those living with and beyond cancer. These include risk-stratified pathways of care, the use of treatment summaries and care plans, information and education to enable choice and the confidence to self manage, rapid re-access to specialist care, remote monitoring and well-coordinated care. Many of these principles are relevant internationally, though preferred models of care will depend on local circumstances.

Whole-body imaging of adoptively transferred T cells using magnetic resonance imaging, single photon emission computed tomography and positron emission tomography techniques, with a focus on regulatory T cells.

Cell-based therapies using natural or genetically modified regulatory T cells (T(regs)) have shown significant promise as immune-based therapies. One of the main difficulties facing the further advancement of these therapies is that the fate and localization of adoptively transferred T(regs) is largely unknown. The ability to dissect the migratory pathway of these cells in a non-invasive manner is of vital importance for the further development of in-vivo cell-based immunotherapies, as this technology allows the fate of the therapeutically administered cell to be imaged in real time. In this review we will provide an overview of the current clinical imaging techniques used to track T cells and T(regs) in vivo, including magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission computed tomography (SPECT). In addition, we will discuss how the finding of these studies can be used, in the context of transplantation, to define the most appropriate T(reg) subset required for cellular therapy.

An exploratory investigation amongst Australian mothers regarding pharmacies and opportunities for nutrition promotion.

The early years life-stage (1 year either side of childbirth) is an important period for preventive action focusing on optimizing nutritional health for mothers and babies. Community pharmacy is a much utilized, easily accessed setting for health promotion and exposure to the primary health care system. The literature suggests that there has been limited exploration of pharmacy utilization by mothers, particularly in the context of nutrition focused health promotion. This study aimed to explore mothers' expectations and experiences of pharmacy based health care and to explore mothers' attitudes and opinions regarding opportunities and scope for nutrition-related health promotion in pharmacy. Qualitative semi-structured telephone interviews were conducted amongst a purposive sample of 28 mothers from across Queensland, Australia. Interviews were transcribed and analysed thematically using an iterative approach. Participants as relatively frequent users of pharmacy services accessed pharmacy for medicines or product related concerns but expected information and health advice to be available. Opportunities for nutrition promotion in pharmacy, identified by participants, related primarily to addressing their personal needs for information, advice and support during this life-stage. Improving and reorienting pharmacy staff practices may contribute to more supportive guidance being provided to mothers in this setting.

Selective removal of uranyl ions using ion-imprinted amino-phenolic functionalized chitosan.

The recovery of uranium from aqueous effluents is very important for both the environment and the future of nuclear power. However, issues of sluggish rates and poor selectivity persist in achieving high-efficiency uranium extraction. In this study, uranyl (UO22+) ions were imprinted on an amino-phenolic chitosan derivative using an ion-imprinting method. First, 3-hydroxy-4-nitrobenzoic acid (HNB) units were joined to chitosan via amide bonding, followed by reducing the -NO2 residues into -NH2. The amino-phenolic chitosan polymer ligand (APCS) was coordinated with UO22+ ions, then cross-linked with epichlorohydrin (ECH), and finally the UO22+ ions were taken away. When compared to non-imprinted sorbent, the resulting UO22+ imprinted sorbent material (U-APCS) recognized the target ions preferentially, allowing for much higher adsorption capacities (qm = 309 ± 1 mg/g) and improved adsorption selectivity for UO22+. The FTIR and XPS analyses supported the pseudo-second-order model's suggestion that chemisorption or coordination is the primary adsorption mechanism by fitting the data well in terms of kinetics. Also, the Langmuir model adequately explained the isotherms, suggesting UO22+ adsorption in the form of monolayers. The pHZPC value was estimated at around 5.7; thus, the optimum uptake pH was achieved between pHs 5 and 6. The thermodynamic properties support the endothermic and spontaneous nature of UO22+ adsorption.

Assessment of factors associated with pre-diabetes in HCV infection including direct and dynamic measurements of insulin action.

Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre-diabetes in this population. We aimed to evaluate factors associated with pre-diabetes in HCV-infected patients, including direct measurement of insulin action. Ninety-seven non-cirrhotic, non-diabetic and HCV-infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady-state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT. Rates of pre-diabetes were as follows: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT) and 9% combined IFG/IGT. Twelve percent of Caucasians, 50% of African Americans and 70% of Latinos had pre-diabetes (P = 0.002). Patient characteristics among the glucose metabolism categories were similar except those with combined IFG/IGT had a higher body mass index (BMI) vs normal glucose tolerance (NGT) (30 vs 26 kg/m(2), P = 0.007) and lower LDL vs NGT and IGT (74, 104 and 112 mg/dL, respectively, P ≤ 0.01). On multivariable analysis, non-Caucasian race (OR 23.1, P = 0.003), BMI (OR 3.4, P = 0.02) and greater liver inflammation (OR 7.9, P = 0.03) predicted IFG, whereas non-Caucasian race (OR 14.8, P = 0.01) and SSPG (OR 1.1 per 10 units, P = 0.01) predicted IGT. Early and total insulin secretion adjusted for the degree of insulin resistance was decreased in pre-diabetes compared with NGT (P = 0.01 and P = 0.02, respectively). Pre-diabetes is highly prevalent among HCV-infected patients, and in some instances, coincides with host responses to the virus. In most cases, however, factors that are associated with pre-diabetes in HCV-infected patients are similar to those observed in the non-HCV population.

Change in extracellular fluid and arm volumes as a consequence of a single session of lymphatic massage followed by rest with or without compression.

PURPOSE: This study evaluated the acute effect of massage and compression components of lymphoedema treatment in women with and without arm lymphoedema secondary to breast cancer from a single treatment session. METHODS: Women with (n = 15) and without (n = 15) lymphoedema underwent a single session of lymphatic massage. Following the session, women were randomised to receive or not receive a compression sleeve. Measurements were taken prior to, during, and following the massage as well as 30 min after completion of the massage. Bioimpedance spectrometry (BIS) was used to measure changes in extracellular fluid volume of all limbs as well as 10-cm segments within the upper limbs; perometry was used to measure changes in total upper limb volume as well as 10-cm segments within the limb. RESULTS: There were no significant changes after massage with or without compression. The median (and interquartile range) BIS ratios (unaffected:affected) for the whole upper limb for women with lymphoedema changed from 1.152 (1.053 to 1.422) to 1.192 (1.045 to 1.410) after massage, while the control group changed from 1.024 (0.998 to 1.047) to 1.041 (0.982 to 1.07). The median change in both the BIS ratio and the total arm volume measured with perometry from prior to the massage to following 30-min rest changed <2%, irrespective of whether women used a compression garment and whether women presented with or without lymphoedema. Examination of 10-cm segments within the arm also revealed no significant change in BIS ratio from one segment to the next. CONCLUSION: Massage alone or the application of compression after a single session of lymphatic massage was ineffective for reducing lymphoedema.

Reverse total shoulder arthroplasty for cuff tear arthropathy: the clinical effect of deltoid lengthening and center of rotation medialization.

BACKGROUND: Reverse total shoulder arthroplasty (RSA) for cuff tear arthropathy improves shoulder function and reduces pain. Implant position and soft tissue balancing are important factors to optimize outcome. Tensioning the deltoid and increasing the deltoid moment arm by medializing the center of rotation are biomechanically advantageous. The purpose of this study was to correlate RSA functional outcomes with deltoid lengthening and center of rotation medialization. MATERIALS AND METHODS: This prospective cohort study enrolled 49 consecutive patients who underwent RSA for cuff tear arthropathy. Preoperative and serial postoperative physical examinations, radiographs, and American Shoulder and Elbow Surgeons and Simple Shoulder Test scores were evaluated. Deltoid lengthening and medialization of the center of rotation were measured radiographically and correlated with functional outcome scores, range of motion, and complications. RESULTS: At final follow-up (average, 16 ± 10 months), 37 of 49 patients (76%) were available for analysis. Deltoid lengthening (average, 21 ± 10 mm) correlated significantly (P = .002) with superior active forward elevation (average, 144° ± 19°). Medialization of the center of rotation (average, 18 ± 8 mm) did not correlate with active forward elevation or subjective outcomes. Deltoid lengthening that achieved an acromion-greater tuberosity distance exceeding 38 mm had a 90% positive predictive value of obtaining 135° of active forward elevation. Two patients (4%) required revision surgery, and 68% of patients developed scapular notching (average grade, 1.3 ± 1.2) at final follow-up. CONCLUSION: Deltoid lengthening improves active forward elevation after RSA for cuff tear arthropathy.

Fractional flow reserve (FFR): changing the practice of interventional cardiology.

Fractional flow reserve (FFR) has become an extremely valuable tool for assessing the hemodynamic significance of intermediate coronary lesions. This manuscript delineates the current guidelines regarding the use of FFR and discusses emerging indications for the use of this diagnostic tool and how they compare with and complement non-invasive or other invasive diagnostic modalities. The manuscript addresses some of the key unanswered questions related to FFR, the potential pitfalls of this tool and discusses future directions of use and research.

Dual antiplatelet therapy for primary and secondary prevention.

The concomitant use of aspirin and an ADP receptor (P2Y12) blocker, also known as dual antiplatelet therapy (DAPT), has been extensively investigated as a primary and secondary prevention strategy in an effort to reduce the risk of cardiovascular events. In this manuscript the authors review the current guideline recommendations for DAPT and discuss the scientific data that supports these recommendations. Reported are also the scientific knowledge gaps and how future studies are likely to delineate these issues. Incremental knowledge is not likely to be an alternative to individualized care provided by the astute clinician to his patient. In consideration for prescribing DAPT (drug, dosage and duration) the clinician will have to weigh the potential benefits (reduction in death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) and risks (severe or life-threatening bleeding) for each and every patient.