Personal Protective Equipment and Fire

How to cite this article: Paliwal B, Bhatia PK, Kamal M, Purohit A. Personal Protective Equipment and Fire. Indian J Crit Care Med 2021;25(4):473

Personal protective equipment (PPE) is worn by healthcare workers to protect themselves from getting infected from the patients. The component of PPE as well as the nature of the material used for PPE is dictated by the disease and its mode of transmission. Coronavirus disease-2019 (COVID-19) infection being an aerosol-transmitted infection mandates PPE consisting of gowns or coverall, head cover, goggles, mask or face shield, gloves, and rubber boots. The stringent standards mandate that coveralls and gowns should be efficient in protecting from exposure to biologically contaminated solid particles and chemical hazards.¹ The guidelines from the Ministry of Health and Family Welfare, India, in accordance with WHO state that “the fabric that cleared/passed ‘Synthetic Blood Penetration Resistance Test’ (ISO 16603) and the garment that passed ‘Resistance to penetration by biologically contaminated solid particles’ (ISO 22612:2005) may be considered as the benchmark specification to manufacture Coveralls.”^1,2 Hence, coveralls for COVID-19 prevention kit are commonly made from high-density polyethylene formed into a nonwoven fabric that allows heat and sweat to leave the suit while preventing liquids and aerosols from entering it.³ The disposable gowns are typically made of polypropylene, polyester, or polyethylene, whereas the reusable ones carry cotton/polyester blends.³While the material used for PPE ensures protection from viral infections, being inflammable, it does not so from fire. One such fire incident has already been reported in a COVID-19 patient–caring hospital. Media reports claimed the blaze spreads after a staff member''s PPE kit caught fire. The paramedic staff whose PPE had caught fire while saving the patient sustained 21% burns needing hospitalization.⁴ In quick succession, another incident of fire is reported in a COVID-19 center, the details of which are awaited.⁵ The inciting event in these incidences may be preventable, but nevertheless considering the compromised vision and hearing in PPE that affect early detection, communication, and response in incidents of fire; it hints to additional consideration of choosing fire-resistant material for PPE. Nomex or flame-resistant cotton may be used for flame-resistant coveralls or aprons.⁶ By varying the fiber type, bonding process and fabric finish can change the properties of the material; these fire-resistant materials can be made to be liquid and aerosol resistant as well.³To conclude, safety concerns may necessitate the material of PPE in COVID-19 care settings to be fire resistant in addition to being liquid and aerosol resistant.     

Focus on the Positive: A Qualitative Study of Positive Experiences Living With Type 1 or Type 2 Diabetes

The purpose of this study was to identify positive experiences associated with diabetes from the perspective of adults diagnosed with type 1 or type 2 diabetes. We conducted in-depth face-to-face and telephone interviews with adults with diabetes. Participants focused on positive and supportive experiences with their peers and community, improved health behaviors, personal growth, and engagement in diabetes advocacy. Communicating positive experiences about diabetes may help clinicians and educators reframe the negative messages commonly shared with people with diabetes.

Diabetes is one of the most significant health problems in the United States and globally. In the United States, an estimated 34.2 million people of all ages—or 10.5% of the population—have diabetes, with the vast majority having type 2 diabetes (1). Diabetes is a group of diseases characterized by high blood glucose levels resulting from the body''s inability to produce or use insulin (2). The two most common forms are type 1 diabetes and type 2 diabetes (2); the former is marked by the body’s inability to produce insulin and the latter by the body’s inability to make enough insulin or to effectively use the insulin it produces (2). Although type 1 diabetes is most commonly diagnosed in childhood or adolescence, it can occur at any age. Likewise, type 2 diabetes is most commonly diagnosed during middle age but can be diagnosed in childhood or adolescence. Recent trends in incidence show increases in both type 1 and type 2 diabetes, especially in children and adolescents (1).Recent data from the Centers for Disease Control and Prevention show that half of U.S. adults with diagnosed diabetes (50.0%) have an A1C value at target (<7.0%) (1). Of these, 19.2% were both nonsmokers and met all three “ABC goals”: A1C <7.0%, blood pressure <140/90 mmHg, and non-HDL cholesterol <130 mg/dL (1). Reaching ABC goals decreases the risk of macrovascular (e.g., cardiovascular disease) and microvascular (e.g., retinopathy, neuropathy, and nephropathy) complications (3–5). Behaviors that promote ABC goal achievement, and in turn reduce the risk for complications, include smoking cessation (6), following a healthy diet (7), losing weight (8), engaging in regular physical activity (9), monitoring blood glucose levels (10), taking medication (11), checking feet (12), and attending clinic appointments (13,14). Active engagement in these behaviors is encouraged in diabetes self-management education and support (DSMES) programs (15,16).DSMES is an important component of care for all people with diabetes (16). DSMES should be person-centered and facilitate learning about diabetes, participating in diabetes decision-making, and acquiring skills for self-care (16). Furthermore, providers who deliver DSMES should incorporate positive, strengths-based language to reduce stigma and feelings of shame and guilt (17,18). Historically, diabetes care and DSMES have focused on behavioral and clinical targets, which may explain their short-term benefits but limited long-term effects on outcomes (19,20). Incorporating personal stories and experiences into diabetes management may help adults with diabetes sustain the benefits they accrue (21–23). However, minimal research has explored positive stories and experiences of living with type 1 or type 2 diabetes. Thus, the purpose of this study was to identify positive experiences with diabetes from the perspective of adults diagnosed with either of these forms of the disease.     

“Counting Carbs to Be in Charge”: A Comparison of an Internet-Based Education Module With In-Class Education in Adolescents With Type 1 Diabetes

Carbohydrate counting is an essential component of type 1 diabetes education but can be difficult for adolescents to learn. Because adolescents are avid users of technology, an Internet-based education module was compared with an in-class education session in terms of carbohydrate counting accuracy in adolescents with type 1 diabetes. Adolescent participants displayed increased carbohydrate counting accuracy after attending an in-class education session compared with an Internet-based education module. These results suggest that online education is best reserved as an adjunctive therapy to in-class teaching in this population.

Carbohydrate counting is a recommended daily practice for the self-management of type 1 diabetes, in conjunction with insulin therapy (1). This method allows for more flexibility in the timing and frequency of eating and the amount of carbohydrate consumed during meals and snacks (1). Accuracy in carbohydrate estimation is required to achieve and sustain adequate glycemic control, and differences of ≥20 g from actual carbohydrate amount have been shown to affect postprandial glucose excursions (2,3). Thus, carbohydrate counting is an essential component of conventional diabetes education, a collaborative process whereby patients gain knowledge and skills to successfully self-manage their diabetes and related conditions (4,5).However, evidence suggests that adolescents with type 1 diabetes do not accurately count carbohydrates (6). In a previous study in adolescents with type 1 diabetes, we reported that, despite using carbohydrate counting for managing their diabetes and receiving in-class education with a dietitian, fewer than half of the sample counted carbohydrates accurately (7). Furthermore, a nutrition education intervention focused on carbohydrate counting in adolescents with type 1 diabetes found no improvement in counting accuracy and glycemic control after 3 months (8). These findings suggest a need to develop more intensive education that is cost-effective and readily available and provides the tools to empower individuals in their day-to-day diabetes management (9,10).Multiple factors have a bearing on the delivery of diabetes care for adolescents with type 1 diabetes; these include a shift in responsibility from parents to adolescents, adolescents’ focus on social contexts and peers, developmental inclination toward risk taking, and fatigue from care of a chronic illness (11). Therefore, the approach to diabetes education needs to be engaging, developmentally appropriate, and motivating to encourage appropriate diabetes self-management.Digital technologies are readily used among adolescents, and strategies that incorporate such technologies can potentially help adolescents enhance their skills in diabetes self-management (12,13). These strategies include online educational resources (14), short message service systems (15,16), interactive diabetes management tools (17), video games (18,19), Internet-based communication (20), Internet videoconferencing (21), and mobile device applications (22). Online education for diabetes management may help to reduce the complexity and inaccuracies associated with carbohydrate counting, as well as reduce the barrier of attending face-to-face teaching sessions by being a flexible learning option that can be reviewed at a patient’s convenience.There is no evidence indicating the most effective type of educational platform for training adolescents in carbohydrate counting. Although studies of Internet-based educational tools for diabetes self-management have been conducted in adolescents with type 1 diabetes (23), none have focused exclusively on improving carbohydrate counting skills. Furthermore, the current literature evaluating computer-assisted diabetes education has primarily targeted adults with type 2 diabetes (24,25). Therefore, the objective of this study was to evaluate an Internet-based education module on carbohydrate-counting accuracy in adolescents with type 1 diabetes in comparison with the standard of care (in-class education session). We hypothesized that the Internet-based module would result in improved accuracy compared with the in-class session.     

Pathogenetic Mechanism of Procalcitonin in COVID-19

How to cite this article: Wiedermann FJ. Pathogenetic Mechanism of Procalcitonin in COVID-19. Indian J Crit Care Med 2021;25(5):594.

Dear Sir,In the Editorial by Savio entitled “Procalcitonin (in COVID-19): The Incessant Quest,” the author wrote that the pathogenetic mechanism for the cause–effect of procalcitonin (PCT) to raise the risk of developing a severe disease remains to be proved.¹The author wants to point to two previously published studies. In the year 2002, the results of an in vitro study revealed that in vitro PCT is a monocyte chemoattractant that deactivates chemotaxis in the presence of additional inflammatory mediators. Nylen et al. demonstrate that increased PCT exacerbates mortality in experimental sepsis, whereas neutralization of PCT increases survival. Thus, PCT, in addition to being an important marker of severity of systemic inflammation and mortality, is an integral part of the inflammatory process and directly affects the outcome.^2,3Our institution has the laboratory possibility to investigate fragments of PCT in a bioassay in order to determine the active part of the peptide PCT. In the future, there is the option to create an agonist and antagonist of PCT. This new molecule should be able to influence the pathogenetic role of PCT in severe sepsis.     

Prevalence of Bloodstream Infections and their Etiology in COVID-19 Patients: A Tale of Two Cities

How to cite this article: Tyagi N. Prevalence of Bloodstream Infections and their Etiology in COVID-19 Patients: A Tale of Two Cities. Indian J Crit Care Med 2021;25(4):355–357.

With 114,477,868 people affected worldwide and 2,539,290 deaths till now, coronavirus disease-2019 (COVID-19) is ravaging as the worst pandemic in human history. The unprecedented burden on the healthcare system as well as human resources has proven catastrophic and the world is still grappling with the seemingly relentless surges in cases. The search for effective antiviral therapy has so far been elusive with some steroids remaining the only class of drug that has shown any mortality benefit. Evidence regarding the use of anti-inflammatory drugs like baricitinib and tocilizumab, particularly in critically ill COVID-19 patients who need mechanical ventilation appears chimera for now, and their likely flip side in terms of impending secondary infections presents a clear danger.¹ In almost all severe cases, SARS-CoV-2 infection results in pneumonia and the inflamed fluid-filled alveolar tissue may turn into an ideal habitat for bacterial pathogens. Thus the causative agent resulting in further worsening of severe disease may be a bacteria or fungi rather than virus itself. Patients with COVID-19 are likely to stay on invasive mechanical ventilation for a long time (mean: 9·1 day), thereby increasing the chances of the hospital and ventilator-acquired infections.While rationing of ventilators and ICU beds in overwhelmed health systems could have resulted in unusually high mortalities during the initial phase of COVID-19, what baffled medical community the most was nihilistic mortality figure of almost 100% amongst patients requiring mechanical ventilation, as reported from China. Half of these COVID-19 fatalities were believed to be due to a certain form of secondary infection (pulmonary or other).² The obvious answer to this problem in using early broad-spectrum antibiotics brings forth the risk of multidrug-resistant (MDR) pathogens. During the 2003 SARS-CoV outbreak, analyses of isolates collected from patients in the intensive care unit (ICU) in Prince of Wales Hospital (Hong Kong) showed increased rates of methicillin-resistant Staphylococcus aureus acquisition from 3.53% pre-SARS to 25.30%. This exponential rise despite adequate infection control practices was largely attributed to higher than usual antibiotic usage during the outbreak.³ With almost all patients being treated with more than one antibiotic right from the time of hospital admission, this ongoing battle with COVID-19 is likely to worsen India''s already dire situation regarding high incidence MDR pathogens.The binary choice about not using antibiotics while awaiting etiology of secondary infection and risking increased mortality vs empirically starting them in severely ill COVID-19 gets confounded by lack of data regarding likely bacterial microbiology. Bacterial coinfection has huge geographic variations due to variability in the proportion of patients tested, the microbiology of bacterial infections, and antimicrobial stewardship policies. Langford et al. have tried to address this gap by adopting a concept of “living rapid review and meta-analysis: bacterial co-infection and secondary infection in patients with COVID-19”, which periodically searches literature and updates findings in 3 monthly fashions. Their first published results from 24 studies representing 3,338 patients, identified bacterial co-infection (estimated on presentation) in 3.5% and secondary bacterial infection (during hospitalization) in 14.3% of the patients. Bacterial infection was more common (8.1%) in critically ill patients, this figure now stands grown up at 16.0% (11.6–20.4) (https://www.tarrn.org/covid). They also highlighted that majority of patients with COVID-19 (71.9%) received antibiotics despite most of the guidelines discouraging their use. The biggest shortcoming was specific species of bacterial co-pathogens being reported in 11/24 studies (45.8%), representing less than 14% of patients with reported infections. The most common organisms reported were Mycoplasma species, Haemophilus influenzae, and Pseudomonas aeruginosa.⁴Initial studies from China although initiated by the world regarding outcomes related to secondary infections lacked microbiological details. A multicenter study that included 476 COVID-19 patients, revealed that critically ill ones had the highest percentage of bacterial coinfections (34.5%) compared to patients in the moderately ill and severely ill groups (3.9 and 8.3%, respectively). This higher rate of coinfections in critical patients was observed despite a majority of them (92.9%) receiving antibiotic treatments compared to 59.4 and 83.3% of the patients in the moderately ill and severely ill groups, respectively.⁵ Zhou et al. observed that among 191 COVID-19 patients, bacterial coinfections occurred in 15% of the cases, including 50% of nonsurvivors, even though 95% of patients had received antibiotics; ventilator-associated pneumonia occurred in 31% of patients requiring invasive respiratory support. Even more troubling was the fact that 27/28 COVID-19 patients with coinfections succumbed.² These studies probably confirm the futility of prophylactic antibiotics when it comes to bacterial secondary infections.Li et al. in a retrospective analysis of about 1500 patients, tried to explore etiology and antimicrobial resistance of secondary bacterial infections (SBI) in patients hospitalized with COVID-19.⁶ They confirmed high mortality (49.0%, 50/102) in those with SBI while the overall percentage who acquired SBI was 6.8% (n = 102) only. Among the 159 strains of bacteria isolated from the SBIs, 85.5% were gram-negative bacteria. The top three strains were Acinetobacter baumannii (35.8%), Klebsiella pneumoniae (30.8%), and Stenotrophomonas maltophilia (6.3%). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Methicillin resistance was present in 100% of S. aureus and coagulase-negative staphylococci. The high antimicrobial resistance rates of major isolated bacteria highlight that the optimizing choice of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19. An Italian study analyzed 731 patients and reported that an overall 28-day cumulative incidence of 16.4% bloodstream infections (BSI) was much higher (7.9 vs 3.0%) than presumed lower respiratory tract infections (pLRTI).⁷ Most of the BSIs were due to gram-positive pathogens specifically coagulase-negative staphylococci (69.7%), while among gram-negatives (21.7%) A. baumannii (30.4%) and Escherichia coli (21.7%) predominated. pLRTIs were caused mainly by gram-negative pathogens (53.8%). Eleven patients were diagnosed with putative invasive aspergillosis, again reminding that geographic variations are a rule rather than an exception.In terms of risk factors male gender, older age, heart diseases, hypoproteinemia, corticosteroid and proton-pump inhibitors, early need for ICU, respiratory failure are reported most frequently.Several studies have shown that sustained and substantial reduction of the peripheral lymphocyte counts, especially CD4 T and CD8 T cells, is representative of the immune suppression stage after the cytokine storm activation phase. The dysregulated immune response may be associated with a high risk of developing a secondary bacterial infection.^7,8Current high antibiotic use in COVID-19 patients admitted to intensive care units, renders culture-based microbiological testing less sensitive. Hence, early diagnosis of co-infection is required, preferably using methods capable of detecting potential pathogens and antimicrobial resistance. This brings to centerstage that we still lack good understanding regarding clinical risk factors for concomitant bacterial infections in COVID-19 patients, and India-specific data on how demographics and medical comorbidities influence bacterial infection risk are much needed. One such study from AIIMS, New Delhi, analyzed positive cultures from hospitalized COVID-19 patients. 15% of ICU patients and 12% of non-ICU patients developed secondary infections.⁹ K. pneumoniae (33.3%) was the most common pathogen, followed by A.baumannii (27.1%), E. coli (16.7%), and P.aeruginosa (11.5%). Overall resistance to third-generation cephalosporins and carbapenems was found to be 64–69%. Amongst gram-positive pathogens isolated were MR-CONS and MSCONS which were sensitive to vancomycin, teicoplanin, tigecycline, linezolid, and daptomycin. The AMR genes encoding for carbapenemases-NDM (71%), OXA-48-like (61%), and extended-spectrum beta-lactamases CTX-M (61%) were found highly prevalent in the respiratory samples tested by FilmArray. While it is understandable that neither European nor Chinese microbiota will have many similarities with Indian ones, a study undertaken in a tertiary care center in Jaipur underscores regional variations likely to be encountered within.¹⁰ The low rate of secondary bloodstream infection (9.4%) has prompted authors to raise a red flag against prophylactic use of antibiotics as well as prompt discontinuation in case they were already started. In contrast, they had a much higher incidence of coagulase-negative staphylococci (CoNS) out of which almost 90% were methicillin-resistant, while pseudomonas species were pan drug-sensitive. This wide variation in local microbiology is of utmost significance since the risk factor including age, gender, and severity of illness in both studies are almost mirror images. The USA is the other country that has reported a higher incidence of these otherwise skin commensal CoNS in COVID-19 patients.¹¹ One probable reason could be poor sampling technique and unless a pathological role is confirmed, treating such isolates is another conundrum that clinicians are likely to face. The possibility of antibiotics administered at admission altering the microbiological and clinical milieu is another way of explaining these findings. To diagnose co-infections early in COVID-19, patients should be screened on admission at the intensive care unit and subsequently sampled throughout the disease course.The use of interleukin 6 (IL-6) inhibitors, such as tocilizumab for COVID-19-related cytokine activation syndrome is going to presents a unique challenge by suppressing common signs of sepsis. Acute-phase reactants including white blood cell count and C-reactive protein may also not rise in response to a secondary bacterial infection after tocilizumab use.¹ Duration of this effect likely to last with 1 or 2 doses is also unclear. Procalcitonin may be less affected by IL-6 inhibitors, but the data to identify secondary bacterial infections in this context are in a nascent stage. Lastly, fungal infections including Candida albicans as well as non-albicans and invasive pulmonary aspergillosis are also being reported in patients with COVID-19-associated acute respiratory distress syndrome.¹² This further necessitates discretion when it comes to the use of broad-spectrum antibiotics in COVID-19 patients.Global pandemics from emerging viruses are inevitable in a world with interconnected societies, transcontinental travel, and intuitive tourism. In order to stay well-prepared for the next pandemic, we must be well informed regarding bacterial pathogens commonly observed in secondary infections to avert a healthcare crisis due to antibiotic-resistance.     

Investigating and Comparing the Effect of Teach-Back and Multimedia Teaching Methods on Self-Care in Patients With Diabetic Foot Ulcers

This study evaluated the effect of teach-back and multimedia teaching methods versus routine care on the self-care of patients with diabetic foot ulcers. Patients receiving either the teach-back or multimedia interventions had greater improvement in self-care scores than those receiving routine care. Both the teach-back and multimedia teaching methods were found to be effective in enhancing the self-care of people with diabetes.

People with diabetes (PWD) account for 7–8% of the total population in Iran (1). PWD are exposed to severe complications such as mental physical problems, including vascular disorders and peripheral neuropathy resulting in diabetic foot ulcers (2–5). Although the number of deaths caused by diabetes complications has decreased in recent years, the number of disabilities caused by diabetes remains high; for example, >70% of amputations are the result of diabetes (6).Diabetic foot ulcers are one of the most important and most common complications of diabetes and the main cause of hospitalization of these patients. Foot ulcers also impose the highest hospital costs on PWD (7). The World Health Organization describes “diabetic foot” as the foot of a person with diabetes who has neurological disorders, some degree of vascular involvement, and susceptibility to infection and ulcer, with or without degradation of deep tissues (8). Diabetic foot ulcers are slow to heal and can disrupt the lifestyle, social activities, health, and quality of life of patients and their caregivers (9). Because of the prevalence of foot ulcers in PWD, we need supportive programs to prevent and control this complication (10).Four risk factors are involved in the development of foot ulcers, including neuropathy, foot deformity, history of previous foot ulcer, and decreased foot circulation. People with these risk factors should receive specific ulcer treatments and implement effective plans to prevent relapse once an ulcer has healed. All PWD—even those without risk factors—need to take good care of their feet because even minor cases can lead to serious problems in these patients (11).Recent studies have shown that several risk factors may be associated with the development of diabetic foot ulcers. Foot ulcers are more common in males, people with longer duration of diabetes (>10 years), older people, those with higher BMIs, and people with other diabetes-associated diseases such as retinopathy, neuropathy, peripheral vascular disease, foot decay, excessive pressure on the soles of the foot (such as from inappropriate shoes and anatomical problems), malnutrition, and infection (12).Diabetes is a chronic disease requiring lifelong adjustment (13). Hence, PWD are expected to carry out rigorous self-care behaviors throughout their life. Evidence has shown that a lack of information and skills needed to manage chronic disease conditions is one of the most important causes of patient noncompliance with treatment and recommendations such as for healthy eating (2).The main goal of diabetes treatment is not only to remove the physical signs and symptoms of the disease, but also to improve the overall quality of life of patients. Self-care is the foundation of health promotion and disease prevention. Thus, providing a self-care educational program helps patients improve their self-care abilities and reduce their fear and dependence, thus enhancing their self-esteem and independence (14). Facilitating the process of self-care can improve the health, economic, and social status of the entire community (15). In addition to reducing hospitalizations, appropriate self-care can prevent many other problems for patients (16). For these reasons, training has a special place in the diabetes treatment process. Having complete information about the overall disease and care is one of the most important rights of patients, and today, patient training is one of the most important care roles and responsibilities of nurses in enhancing patients’ health and ability to adapt to the effects of the disease (17).Training patients via electronic platforms is a new teaching method that allows for the transfer of the concepts and materials in a simpler, more accessible, and more appealing manner. Digital education can involve text, sounds, images, and video elements (18). One form of modern digital teaching is known as the multimedia method (17,19). Multimedia is considered to be an individual teaching method. It is a type of e-learning in which learners learn how to learn (20). Another teaching approach to ensure patient understanding and retention of information is the teach-back method (21). Studies conducted by Oshvandi et al. (22) on heart failure, diabetes, and dialysis patients, respectively, showed that the teach-back teaching increased patients’ self-care behaviors. None of the studies in this area to date have compared the effects of the two teaching methods (teach-back and multimedia) on self-care in PWD.     

Role of Prophylactic Noninvasive Ventilation in Patients at High Risk of Extubation Failure

How to cite this article: Singh L. Role of Prophylactic Noninvasive Ventilation in Patients at High Risk of Extubation Failure. Indian J Crit Care Med 2020;24(12):1158–1160.

Prolonged mechanical ventilation (MV) has serious side effects and complications. Thus, one opts for an early extubation after correcting the causes and stabilizing the patient.¹ Extubation is commonly uneventful especially in an odds ratio (OR) but in intensive care unit (ICU) it is often associated with respiratory failure development post post extubation which may very often require reintubation. The rule of thumb about reintubation risk cannot be applied to all patients as the pathophysiology of extubation failure is poorly understood.An average of 15% patients may need reintubation among which 25–30% are at high risk.¹ The high-risk patients of extubation failure include preterm infants, age ≥65 years, any respiratory disease, cardiac disease.² A major cause of weaning failure is acute respiratory failure (ARF) due to respiratory muscle fatigue or increased work of breathing due to decreased pulmonary compliance or increased resistance. Other causes include inadequate cough, airway obstruction, excess secretions, neurologic impairment. An important factor responsible for mortality in ICU patients after extubation is ARF. Noninvasive ventilation (NIV) is used for both management and prevention of post-extubation respiratory failure.After extubation, oxygenation can be improved by three methods available: conventional oxygen therapy, high-flow oxygen therapy, and NIV. Respiratory support is most commonly provided by conventional oxygen therapy. However, in recent years, high-flow oxygen therapy (HFOT) and NIV are being used increasingly. These methods are speculated to prevent extubation failure by promoting alveolar recruitment, preventing alveolar collapse, and reducing the work of breathing. Noninvasive ventilation (NIV) causes an increase in the intrathoracic pressure preventing alveolar collapse, improving oxygenation, and reducing the workload of the heart. It also prevents complications of invasive MV.³ The protocol of using prophylactic NIV can involve the immediate application of NIV within 1 hour of extubation for a duration of 8–24 hours depending upon the improvement in the respiratory parameters, such as, respiratory rate, pH, partial pressures of oxygen, and carbon dioxide. The prophylactic use of NIV has been adopted for reducing the rates of reintubation, duration of MV, and improving the overall prognosis of patients at high risk of post-extubation failure.^1,3–5The International Consensus Conference in intensive care medicine in 2001 suggested that NIV is a promising therapy to prevent respiratory failure after weaning.⁶ It can ameliorate some of the pathophysiologic derangements that occur following extubation. It has been used as an adjunct to weaning or as a part of early extubation approach.Since the need for reintubation has been associated with significantly poor outcomes in terms of prolongation of the ICU stay, hospital stay, use of MV and its associated complications like pneumonia and lung damage, the requirement of tracheotomy, and financial implications, two studies have used different methods for preventing it; among which the prophylactic use of NIV has been found to be is successful.^4,5,7 The successful use of prophylactic NIV has been most pronounced in high-risk patients of extubation failure.⁸ Post-extubation respiratory failure and reintubation prevention by using NIV is supported by weak evidence. NIV can decrease reintubation rates was concluded in two meta-analyses, but these studies had both high risk (only 35%) as well as the general population.^9,10 NIV compared to with conventional oxygen therapy in ICU patients at high risk of reintubation was found to be more effective.⁴ However, a meta-analysis conducted in 2014 with 1,382 patients found that the use of NIV as a preemptive measure after extubation or after respiratory failure which developed post-extubation was not beneficial either in reducing mortality or intubation rate.¹⁰Liu et al.³ found that prophylactic NIV brings about a significant reduction in the atelectasis (OR = 0.43, p = 0.02) and rate of reintubation (OR = 0.33, p = 0.02). The reduction in atelectasis rate is an additional advantage since the development of atelectasis is associated with further complications, such as, pneumonia and atelectrauma.¹¹ One of the previous review studies backed up the improved outcomes of the use of prophylactic NIV in major abdominal surgeries.¹² This was even seen on the patients undergoing cardiothoracic surgeries where prophylactic NIV reduced the rate of reintubation.¹³ In a landmark study by Thille et al.¹ which compared the use of prophylactic NIV in 150 high-risk extubated patients with 83 control extubated patients in an ICU setting, there was a significant reduction in reintubation in the study group (15% vs 28%, p = 0.02). The study is important since it included high-risk patients with cardiac disease and respiratory disease, and found that prophylactic NIV was an independent predictor of extubation success. Their findings were backed up by two studies prior to before it which showed a significant reduction in the reintubation from 24 to 8%, p = 0.027 and from 39 to 5%, p = 0.016, respectively.^4,5In an RCT, Ferrer et al.¹⁴ concluded that early use of NIV averted respiratory failure after extubation and decreased mortality in high-risk patients. Another RCT of 648 patients at high risk of extubation failure concluded that the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation.¹⁵ Nava et al. in a randomized controlled trial studied the use of prophylactic NIV in patients at high risk of extubation failure following at least 48 hours of invasive ventilation and extubation after a successful spontaneous breath trial. They observed that the rate of reintubation was significantly lower in the prophylactic NIV group (8%) compared to with the control group (24%) and NIV was associated with significantly lower ICU mortality and ICU length of stay.⁴ Ferrer et al.¹⁴ applied NIV immediately post-extubation, with age >65 years and APACHE II score >12 at extubation as a factor for high risk of extubation failure and observed that post-extubation respiratory failure was lower in the NIV group (16% vs 33%) but there was no difference in the rate of re-intubation and ICU mortality and 90-days mortality was significantly lower in NIV group. Ferrer et al. in their RCT, used prophylactic NIV in patients with underlying chronic respiratory illness and hypercapnia at extubation. Prophylactic NIV was associated with lower respiratory failure at 48 hours post-extubation and significantly lower 90-day mortality.¹⁶In this issue, Ghosh et al.¹⁷ studied outcomes of prophylactic NIV at extubation after a planned extubation, in patients at a high risk of extubation failure. They observed extubation success in 88.2% of patients at 72 hours. Higher age, longer duration of invasive ventilation, and higher SOFA score at extubation were the factors associated with extubation failure. They also observed organ failure and higher cumulative fluid balance in the first 72 hours post-extubation in the extubation failure group. Ghosh et al.¹⁷ and Upadya et al.¹⁸ observed in their studies that higher cumulative fluid balance at extubation was an independent risk factor for extubation failure in patients after planned extubation.Among the newer modalities, Ali et al.¹⁹ studied the use of nasal high-frequency oscillatory ventilation (NHFOV) as a prophylactic NIV or “rescue mode of NIV” after extubation. The NHFOV is a “noninvasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface”. The results were promising which showed a decreased requirement of reintubation. It is suggested that NHFOW may be a feasible modality that in is being used as prophylactic NIV following extubation for the prevention of apnea and reintubation. But still, the practical applications need randomized controlled trials to lay down the indications and guidelines for its use in other populations. Prophylactic NIV has emerged as an promising modality and its practical use is welcome. Its efficacy has been seen in diverse age groups ranging from pediatric to adults to elderly.Appropriate patient selection, i.e., those who are at high risk of extubation failure is important, because it is not useful in low-risk patients, but also that its use may be detrimental in some patients.     

Quest of Knowledge and Perceived Barriers toward Early Mobilization of Critically Ill Patients in Intensive Care Unit: A Continuing Journey!

How to cite this article: Daptardar AA. Quest of Knowledge and Perceived Barriers toward Early Mobilization of Critically Ill Patients in Intensive Care Unit: A Continuing Journey! Indian J Crit Care Med 2021;25(5):489–490.

Critically ill patients require intensive management before they can recover. Management is even more challenging if they need mechanical ventilation. Early mobilization (EM) in the intensive care unit (ICU) is a physical activity performed as early as the second to fifth day after ICU admission to bring about physiological changes.^1,2EM is defined as mobilization within 72 hours of ICU admission, which is feasible and well-tolerated by most patients once they are stable. It has been difficult to interpret the therapeutic effects of EM due to variations in study populations, interventions, and outcome measures. It has been estimated that up to 46% of ICU patients acquire ICU-acquired weakness, which includes polyneuropathy, myopathy, and/or muscular atrophy during their stay.^3,4 This may have a detrimental effect on the patient''s long-term physical and cognitive functions. Many studies have reported range of motion (ROM) exercises to combat this. The European Society of Intensive Care Medicine has recommended early physical rehabilitation for ICU patients. This has been associated with improved physical function.⁵ Other studies have reported a variety of benefits of EM, which includes reduced mechanical ventilation days, reduced length of ICU stay, reduced hospital length of stay, and improved functional outcomes.^6–8In spite of its potential benefits, EM is not widely performed in the ICU as seen from many international multicenter studies on EM in the ICU, which portrays a low prevalence of out-of-bed mobilization, especially among patients on mechanical ventilation.^9,10 The reason for this may be that mobilizing patients in the ICU is a complex task and is associated with a lot of risks. Equipment and catheters attached to patients can become dislodged causing injury. Critically ill patients who are hemodynamically unstable can also be adversely affected due to mobilization.A growing body of evidence shows the long-term benefits of EM on patient safety, feasibility, functional capacity, strength, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and mortality.^11,12 However, most studies detected considerable barriers to the EM of critically ill adult patients admitted to the ICU which included availability of staff, equipment, oversedation, and lack of education regarding feasibility and safety of EM.In this issue of the journal, a study conducted in the ICU of Tertiary Health Care Academic Institute of Central India, the authors found that majority of members of the multiprofessional team agreed and viewed EM under mechanical ventilation as important and beneficial.¹³ They were knowledgeable about EM and agreed that the benefits of EM outweighed the risks to patients under MV. Similar results were reported in a previous study that analyzed the knowledge and attitudes of multiprofessional healthcare members working in the ICU and delivering care to critically ill patients.¹⁴ The multiprofessional participants in the present study identified several barriers to EM on three levels: (1) Patient-related, such as patient symptoms and conditions, excessive sedation, endotracheal tubes, monitors, and catheters. (2) Provider level barriers, such as limited human and technical resources, limited staffing, and insufficient training. (3) Institutional level barriers related to the ICU culture, lack of proper guidelines, lack of coordination, conflicts of timings of different procedures, and lack of rules for the distribution of tasks and responsibilities.¹³ Similar barriers were also detected in the previous study.¹⁵ In the present study three fourth of the physicians agreed that ROM exercises were sufficient to maintain muscle strength whereas more than half of the physiotherapists and nursing staff disagreed with this. More than half of the physicians were willing to modify the patient level barriers by altering the ventilator settings and reducing sedation to facilitate EM. Although EM was shown to be safe and feasible for patients, there is no information about the staff safety, which was evident by the majority of nursing staff and physiotherapists showing concerns regarding the risk of injuries to the ICU staff during EM. They also reported work stress and long working hours, which might also constitute a considerable barrier to EM in the ICU.¹³The present study confirms that while knowledge continues to advance, practice always remains a step behind, and hence, there is a wide gap between evidence-based knowledge and its application in clinical practice. The study had a small sample size resulting in a selection bias and provided a baseline from one institution only, thus not reflecting the views of other institutions and disciplines. Hence, a multicentre research with a larger sample size or randomized controlled trials is needed to study and evaluate the effects of EM in the ICU using a standardized protocol to determine the optimal timing, intensity, duration, exercise dosage, and progression of mobilization to optimize patient''s physical condition during critical illness.¹⁶     

Understanding the Role of Blood Vessels in the Neurologic Manifestations of Coronavirus Disease 2019 (COVID-19)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally identified as an outbreak in Wuhan, China, toward the end of 2019 and quickly became a global pandemic, with a large death toll. Originally identified as a respiratory disease, similar to previously discovered SARS and Middle East respiratory syndrome (MERS), concern has since been raised about the effects of SARS-CoV-2 infection on the vasculature. This viral-vascular involvement is of particular concern with regards to the small vessels present in the brain, with mounting evidence demonstrating that SARS-CoV-2 is capable of crossing the blood-brain barrier. Severe symptoms, termed coronavirus disease 2019 (COVID-19), often result in neurologic complications, regardless of patient age. These neurologic complications range from mild to severe across all demographics; however, the long-term repercussions of neurologic involvement on patient health are still unknown.

Currently, there are approximately 140 million confirmed infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, and about 3,000,000 deaths associated with SARS-CoV-2 infection (Johns Hopkins University & Medicine, Coronavirus Resource Center, https://coronavirus.jhu.edu, last accessed April 17, 2021) manifesting as severe coronavirus disease 2019, or coronavirus disease 2019 (COVID-19). Approximately 15% of individuals affected by COVID-19 develop severe disease, and 6% are critically ill, resulting in respiratory failure and/or multiple organ dysfunction or failure.¹ The original outbreak of SARS-CoV-2 infection originated from Wuhan, Hubei province, China, in late 2019.^2,3Genomic characterization indicates that bats and rodents are the likely gene sources of α- and β-coronaviruses (CoVs), whereas γ- and δ-CoVs likely arise from avian sources.⁴ To date, seven human coronaviruses have been identified with the ability to cause respiratory, enteric, hepatic, and neurologic diseases in different animal species, including cattle and cats. These viruses are responsible for about 5% to 10% of acute respiratory infections, including the common cold.^4,5 SARS-CoV-2 is a member of the β- coronaviruses and is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with high sequence homology.⁶ These coronaviruses appear to infect the respiratory and gastrointestinal tract, with patients presenting symptoms of fever, cough, and shortness of breath, whereas less common symptoms include diarrhea, vomiting, and nausea.⁷ In addition, cytokine release syndrome was found to be the major cause of morbidity in patients infected with SARS-CoV and MERS-CoV.⁸Aside from the respiratory system, with acute respiratory distress syndrome affecting roughly one-third of COVID-19 hospitalized patients,⁹ COVID-19 appears to also involve multiple organ systems with pathologic manifestations, including the heart, kidney, and brain.10, 11, 12, 13, 14 Because of the multiorgan involvement of COVID-19, it has been hypothesized that COVID-19 is a vascular disease that primarily affects endothelial cells.^15,16 These organs, and their associated blood vessels, may be affected by direct viral tissue injury and localized disordered cytokine release.¹⁷ This direct injury and release of inflammatory and apoptosis inducing mediators leads to localized microvascular inflammation, which triggers endothelial activation, leading to vasodilation and prothrombotic conditions, which cause increased patient mortality.¹⁸Viral infections of the brain are less common than those of other organs as they involve penetration of the blood-brain barrier (BBB). Several viruses, including polio and West Nile virus, are able to cause neurologic complications, but the reasons why they occur in <1 in 100 patients are not understood.¹⁹ The route of entry of the virus into the brain, such as in the blood supply, or by direct infection of vascular endothelial cells, plays a role in the number and type of neurologic symptoms presented by the patient.^19,20 Investigations into MERS-CoV indicated that viral particles enter the bloodstream and are able to infect endothelial cells.²¹ In the case of SARS-CoV-2, viral-like particles have been seen in brain capillary endothelium and actively budding across endothelial cells.²²Although the route of entry of the virus may still be unknown, recent publications have highlighted neurologic manifestations that have been observed in 42% of COVID-19 patients at disease onset, 63% during hospitalization, and 82% at some time during the course of the disease.^23,24 In addition, a significant link was seen between magnetic resonance imaging abnormalities and persistent neurologic deficits, which continued 3 months after disease onset in 55% of patients.²³This review explores the role of the vasculature, specifically within the context of the neurologic manifestations of COVID-19. Herein, the neurologic manifestations reported with SARS-CoV-2 infection are reviewed. The evidence that suggests blood vessels are involved in SARS-CoV-2 infection is surveyed. Finally, the multiple pathologic processes (thromboembolic, inflammatory, and secondary processes) within blood vessels that may contribute to the neurologic manifestations of COVID-19 infection are considered.     

COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Patients with coronavirus disease 2019 (COVID-19) who are critically ill develop vascular complications characterized by thrombosis of small, medium, and large vessels. Dysfunction of the vascular endothelium due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express angiotensin-converting enzyme 2, the receptor that SARS-CoV-2 uses to gain entry into cells, or express it at low levels and are resistant to the infection. These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated locally by an augmented inflammatory reaction to infected nonendothelial cells, such as the bronchial and alveolar epithelium, and systemically by the excessive immune response to infection. Herein we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease.

Following an initial outbreak of pneumonia in Wuhan, China, in December 2019,¹ coronavirus disease 19 (COVID-19) has spread rapidly worldwide, infecting more than 186 million people (Johns Hopkins Coronavirus Resource Center, https://coronavirus.jhu.edu, last accessed July 12, 2021). Caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),² the COVID-19 pandemic has put a major strain on the healthcare systems, causing a global health crisis of unparalleled proportions in modern times.³ Although most patients have recovered from the infection, many experienced a severe form of the disease that requires hospitalization and intensive care, and >3.2 million people have died. Individuals at greatest risk for the fatal complications of COVID-19 have been the elderly and those with underlying conditions, such as lung disease, hypertension, obesity, and diabetes.⁴Clinical manifestations of COVID-19 in severely ill patients are adult respiratory distress syndrome and multiorgan system failure.^4,5 The clinical course of the disease can be complicated by vascular events, including thrombosis of small, medium, and large blood vessels and thromboembolism.^6,7 Although the primary target of SARS-CoV-2 is the respiratory and alveolar epithelium,⁸ the frequent occurrence of vascular complications in COVID-19 has led to the hypothesis that dysfunction of the endothelium, the inner lining of blood vessels, plays an important role in the progression of this disease into a debilitating and lethal condition.⁹ Two potential mechanisms have been hypothesized to explain how SARS-CoV-2 causes endothelial dysfunction and thrombosis. In the first scenario, SARS-CoV-2 directly infects the endothelium, disrupting its antithrombogenic and barrier properties. The second scenario invokes an indirect mechanism of endothelial injury mediated by the local and systemic inflammatory response to the viral infection.^10,11 In this article, we briefly review the vascular pathology of COVID-19 and critically discuss the proposed mechanisms by which SARS-CoV-2 damages blood vessels, including recent studies that challenge the viral infection of endothelium hypothesis and strongly favor an indirect, inflammation-driven mechanism of endothelial injury.     

Corona Collateral Damage Syndrome: Perception of the Damage

How to cite this article: Ahmed A. Corona Collateral Damage Syndrome: Perception of the Damage. Indian J Crit Care Med 2021;25(4):358–359.

The world has been reeling under the coronavirus disease-2019 (COVID-19) pandemic, and none have remained unaffected, directly or indirectly, by this novel severe acute respiratory syndrome coronavirus-2. With its high velocity of spread and magnitude, it has had a significant impact on the healthcare delivery system and posed a challenge across the globe. With over 115 million cases around the world and mortality figures of 2.5 million and counting, countries continue to fight this once-in-a-century-time pandemic.¹ The COVID-19 infection has had a direct negative effect on public health, social welfare and economy.The other major concern has been the collateral impact on non-COVID-19 patient care, namely the corona collateral damage syndrome (CCDS), which has been predicted to have a higher mortality than COVID-19 itself, and it is also difficult to measure.² This clinical condition results from delay or avoidance of seeking medical care for non-COVID-19 acute emergency conditions and has been attributed to fear of patients getting infected on coming to the hospital and social stigma attached to it. This was further reinforced by policies like lockdown and directives of staying indoors.However, there is another cause, and it is related to a change in priorities of working, drastic shift in the working pattern, and focus on healthcare institutions, i.e., managing only COVID-19 patients at the cost of non-COVID-19 medical and surgical patients. It was based on the giant surge and wave of patients suffering from COVID-19 infection, who were getting admitted and overwhelming the healthcare services in certain nations. Healthcare systems adopted an overcautious and defensive approach so as not to exhaust the medical services and preserve its resources and manpower from the jaws of COVID-19.³ Fear was also an underlying factor in the minds of all healthcare workers (HCWs), and it was about perceptions of the worst and the unknown.In this current edition, Swagata et al.⁴ have surveyed the perceptions that HCWs carried about the impact of the COVID-19 pandemic on the delivery of acute care services for non-COVID-19 patients and the reason for its change. Set in within 2 months of the lockdown when all HCWs were grappling and gearing up at various fronts, to counter and adapt to this unknown and unanticipated challenge, which came in like a violent storm, this prospective study has made a fair effort to assess how these perceptions were influenced by HCWs and institutional characteristics, at a time when the visibility on future was unclear. The authors have done a remarkable job by doing the electronic survey and received 392 responses (32.1%) with an 84.1% completion rate over a three-week period during the busy peak time. The number of participants is also comparable to other studies done during this period. As per their study, 60.1% of HCWs perceived a reduction in patient visit to the hospital. It shows that the HCWs were quite aware of the possible impact of this pandemic on the various fronts as was evident in the answer to the questions, and this study could measure this awareness with evidence. Studies have highlighted the marked decrease in the number of patients visiting hospitals, and the outpatient department visits have been affected up to 92%.⁵ A 50% reduction in number was seen in patients attending hospital for a cardiac ailment, whereas the cancer-related services were also down by 27%.^6,7 Effect of the pandemic has also been evident on patients with kidney diseases where almost 28.2% of patients missed one or more dialysis services while 4.13% did not turn up at all, further substantiating the CCDS.⁵Regarding the reasons for changes in service provision and utilization, 58% of HCWs in this study attributed it to lockdown and the fear of infection along with the social nuances. This corroborates with the findings of the Society for Cardiovascular Angiography and Interventions consumer survey determining the fears of the people related to the COVID-19 pandemic.⁸ They had reported that 61% of patients feared contracting an infection if they visited the hospital and 57% wanted to avoid urgent medical attention. 52% of people feared COVID-19 more than heart attack and stroke and that was the magnitude of the fear and uncertainty.While most studies during that period looked at the perceptions regarding the behavior and stress of HCWs, the current study, in addition to the above-mentioned studies, included the HCWs perceptions about the impact on acute healthcare services along with the reason for such a change.In this present study, 56.1% of HCWs avoided duty, when it was evaluated in terms of the perception of HCWs’ behavior. These findings were consistent with the observational cross-sectional study by Kumar et al. that was done on 329 HCWs.⁹ They reported that 65% of doctors were reluctant to work during the pandemic in their study. The fear factor was as high as 84.8% as compared to 50.1% seen in the study by Swagata et al. Even the fear for their family and reluctance to work were higher at 94.2% against the 60.2% reported in the current study. Now, these observations were inevitable and have again been highlighted by this study; given the tough and challenging responsibility, the HCWs were shouldering amidst the uncertainties and many unanswered questions. Chatterjee et al.¹⁰ and similar studies have reported that almost 34.9% of HCWs perceived depression while an equal number felt stress and anxiety. Interestingly, lack of protective equipment and high workload were not perceived as contributors to CCDS in the current study contrary to the other published reports.The current study was conducted using a questionnaire-based survey done on a small population that was of mixed variants and in a short period of time. The selection bias and volunteer effect hence cannot be negated completely. Another limitation has been that this study has not touched upon the objective impact of the perceptions of healthcare workers on acute care services related to cardiology, oncology, surgery, and nephrology. It would have been more complete if the respondents had also been asked about the percentage change that was expected, and then the actual impact on the care of patients and effect could have been measured as a follow-up of this study.This once in a century situation has had no parallels. With passing time, there will be better clarity regarding the understanding of the disease process and it''s trend. It will improve the knowledge, attitude and also change the perception which will allay the fear of the unknown. With the successful advent of vaccination and the better gearing up of resources, there is a fresh ray of hope regarding the control of this pandemic.     

Enzymatically Inactive Tissue-Type Plasminogen Activator Reverses Disease Progression in the Dextran Sulfate Sodium Mouse Model of Inflammatory Bowel Disease

Enzymatically inactive tissue-type plasminogen activator (EI-tPA) does not activate fibrinolysis, but interacts with the N-methyl-d-aspartate receptor (NMDA-R) and low-density lipoprotein receptor–related protein-1 (LRP1) in macrophages to block innate immune system responses mediated by toll-like receptors. Herein, we examined the ability of EI-tPA to treat colitis in mice, induced by dextran sulfate sodium. In two separate studies, designed to generate colitis of differing severity, a single dose of EI-tPA administered after inflammation established significantly improved disease parameters. EI-tPA–treated mice demonstrated improved weight gain. Stools improved in character and became hemoccult negative. Abdominal tenderness decreased. Colon shortening significantly decreased in EI-tPA–treated mice, suggesting attenuation of irreversible tissue damage and remodeling. Furthermore, histopathologic evidence of disease decreased in the distal 25% of the colon in EI-tPA–treated mice. EI-tPA did not decrease the number of CD45-positive leukocytes or F4/80-positive macrophage-like cells detected in extracts of colons from dextran sulfate sodium–treated mice as assessed by flow cytometry. However, multiple colon cell types expressed the NMDA-R, suggesting the ability of diverse cells, including CD3-positive cells, CD103-positive cells, Ly6G-positive cells, and epithelial cell adhesion molecule–positive epithelial cells to respond to EI-tPA. Mesenchymal cells that line intestinal crypts and provide barrier function expressed LRP1, thereby representing another potential target for EI-tPA. These results demonstrate that the NMDA-R/LRP1 receptor system may be a target for drug development in diseases characterized by tissue damage and chronic inflammation.

The inflammatory bowel diseases (IBDs), such as Crohn disease and ulcerative colitis, are chronic, relapsing diseases of the intestines that eventually compromise tissue structure and function.¹ Disease susceptibility genes such as the pattern recognition receptor, nucleotide-binding oligomerization domain containing 2 (NOD2), have been implicated in Crohn disease.^1,2 Dysbiosis in intestinal microbiomes also has been implicated in the onset of IBD, together with lifestyle choices, such as cigarette smoking.3, 4, 5 Once IBD is established, chronic inflammation and tissue damage dominate the clinical course and are principal targets for therapeutics development.⁶ Despite the availability of numerous drugs, many patients with moderate to severe IBD fail to remain in remission and often experience damaging flares.Tissue-type plasminogen activator (tPA) is a serine protease and major activator of the fibrinolytic system.^7,8 Recombinant tPA is Food and Drug Administration-approved for treating recent-onset stroke.⁹ The structure of tPA includes multiple domains that participate in noncovalent fibrin binding, which is essential for restricting the lytic activity of tPA to fibrin while sparing fibrinogen.10, 11, 12 tPA also binds to cell surface receptors, including the N-methyl-d-aspartate receptor (NMDA-R) and low-density lipoprotein receptor–related protein-1 (LRP1), which function as part of a single system to regulate cell signaling and cell physiology.13, 14, 15, 16, 17 Enzymatically inactive tPA (EI-tPA), in which the enzyme active site serine is mutated to alanine, interacts with the NMDA-R/LRP1 receptor system equivalently to enzymatically active tPA to trigger signal transduction.^16,18,19In mouse macrophages, EI-tPA binding to the NMDA-R/LRP1 receptor system blocks inflammatory cytokine expression elicited by multiple toll-like receptors (TLRs), including TLR4, TLR2, and TLR9.18, 19, 20 EI-tPA also blocks the toxicity of lipopolysaccharide in vivo in mice.¹⁸ These results suggest that EI-tPA and the NMDA-R/LRP1 receptor system constitute a novel pathway for regulating innate immunity and inflammation. EI-tPA does not activate plasminogen, thus avoiding undesirable effects on hemostasis and the possible proinflammatory activity of plasmin.^21,22 Some pattern recognition receptors outside the TLR family, such as NOD1 and NOD2, are not antagonized by EI-tPA in macrophages.¹⁹ Furthermore, because the NMDA-R is expressed by numerous cell types,^17,18,23,24 EI-tPA may regulate inflammation by targeting cells in addition to macrophages. Thus, it is not clear whether EI-tPA would be effective in counteracting pathologic conditions in which diverse pattern recognition receptors function together in diverse cells to stimulate fulminant inflammation.In this study, the dextran sulfate sodium (DSS) preclinical mouse model of colitis was used to test the activity of EI-tPA. DSS causes a chemically-induced form of colitis, in which extensive inflammatory cell infiltrates develop in the mucosa and submucosa.²⁵ Mice were treated systemically with a single dose of EI-tPA after intestinal inflammation was established. EI-tPA rapidly reversed signs and symptoms of the disease and caused significant improvement in disease biomarkers. These results indicate that EI-tPA may be efficacious as a therapeutic for complex inflammatory diseases.     

Is it Time to Go Back to Basics?

How to cite this article: Chaturvedi A, Trikha A. Is it Time to Go Back to Basics? Indian J Crit Care Med 2021;25(5):598.

Sir,We read with interest the article by Piazza et al.¹ in JAMA on arterial and venous thrombosis in COVID-19 patients. We wish to share our clinical observation and experience regarding arterial thrombosis in critically ill COVID-19 patients. We have come across three severely ill COVID-19 patients who had developed radial artery thrombosis following radial artery cannulation. Of these, two developed gangrenous changes despite being on standard therapeutic doses of low-molecular-weight heparin. The two patients who developed these gangrenous changes had thrombus of ulnar artery as evidenced by the Doppler study done after the onset of gangrene. The third patient developed minimal discoloration of the index and the ring finger within few hours of radial artery cannulation. The arterial cannula was removed, and the Doppler study revealed radial artery thrombus and a sluggish flow in the ulnar artery. Confirmation of thrombosis was based on Doppler ultrasonography (USG) in all three patients. An important observation was that all three patients had elevated D-dimer values on admission, as well as raised serum interleukin-6 and ferritin values. Raised D-dimer is similar to the findings of Piazza et al.¹ The authors recommended thromboprophylaxis in critically ill COVID-19 patients. However, our patients developed thrombosis despite thromboprophylaxis. We suggest and have started a practice of doing modified Allen''s test in such patients prior to radial artery cannulation. This test despite being far from foolproof is a simple and quick bedside test for assessing the presence of collateral circulation.² It can be performed in conjunction with observation of the plethysmograph on pulse oximetry, in patients at high risk of thrombosis. When indicated, the diagnosis can be supported by the use of Doppler USG for confirmation. We thus recommend performing the modified Allen''s test and observing the plethysmograph in all critically ill COVID-19 patients with raised inflammatory markers prior to arterial cannulation to further safeguard against this dreaded complication.     

Leveraging Technology to Improve Diabetes Care in Pregnancy

Pregnant women with diabetes are at higher risk of adverse outcomes. Prevention of such outcomes depends on strict glycemic control, which is difficult to achieve and maintain. A variety of technologies exist to aid in diabetes management for nonpregnant patients. However, adapting such tools to meet the demands of pregnancy presents multiple challenges. This article reviews the key attributes digital technologies must offer to best support diabetes management during pregnancy, as well as some digital tools developed specifically to meet this need. Despite the opportunities digital health tools present to improve the care of people with diabetes, in the absence of robust data and large research studies, the ability to apply such technologies to diabetes in pregnancy will remain imperfect.

Diabetes is a global health problem affecting ∼60 million women of reproductive age (18–44 years of age) (1). Diabetes during pregnancy, whether preexisting or gestational diabetes mellitus (GDM), confers significant risk to women and their offspring. Pregnant women with diabetes have higher rates of iatrogenic preterm birth (2), preeclampsia, gestational hypertension (3,4), and cesarean delivery (5) compared with gravidae without diabetes. In addition, babies born to individuals with diabetes in pregnancy have greater susceptibility for growth abnormalities, neonatal hypoglycemia, hyperbilirubinemia, shoulder dystocia, and stillbirth (6).Studies of human pregnancies and research conducted in animal models of diabetes in pregnancy have revealed that hyperglycemia is a causative factor for adverse maternal and neonatal outcomes (7). Maintaining good glucose control (euglycemia) has been shown to mitigate these effects. However, euglycemia is difficult to sustain because pregnancy is characterized by physiological insulin resistance, hyperglycemia, and carbohydrate intolerance as a result of diabetogenic placental hormones (8). In women with normal pancreatic function, insulin production is sufficient to meet this challenge; in women with diabetes, hyperglycemia occurs if treatment is not adjusted appropriately and frequently.Successful pregnancy outcomes in the context of diabetes require reducing A1C, decreasing glycemic variability, and increasing the amount of time spent within a target glycemic range. To attain these clinical goals, women must monitor their blood glucose more frequently, improve their nutrition habits, and enhance their physical activity levels. In addition to comprehensive blood glucose monitoring (BGM), women with diabetes in pregnancy are expected to attend more frequent in-office health care visits than expectant mothers without diabetes. Patients describe significant burdens associated with the testing and reporting of blood glucose values in pregnancy, as well as increased demands of attending in-person health consultations (9,10).For women whose access to high-quality care is limited, diabetes in pregnancy presents an even greater challenge. Minority women and those of lower socioeconomic status are often disproportionately affected by both preexisting diabetes and GDM and have higher rates of diabetes-associated morbidity and mortality (11). Given that women from these vulnerable populations already experience greater rates of preterm birth, stillbirth, and maternal mortality (12,13), observance of the often-stringent BGM, medication modification, and face-to-face mediation regimens essential to reducing diabetes-associated adverse pregnancy outcomes can be difficult to achieve or maintain and, in some cases, may be unattainable.Technological innovations, including smartphone applications (apps) and cellular-enabled blood glucose monitors, present opportunities to improve the delivery of care for all women with diabetes in pregnancy. In addition, artificial intelligence and telemedicine can offer an alternative to in-office visits, extending the reach of diabetes education and support while maintaining standards of care (14). Specifically, apps that aid in managing diabetes in pregnancy have the potential to significantly increase patient engagement. Approximately 92% of reproductive-age women in the United States have smartphones, with usage consistently high (66–95%) across racial/ethnic groups and socioeconomic classes (15). Leveraging the availability and pervasiveness of smartphones has empowered patients to become more proactively engaged in their health care and dramatically changed medical practice and biomedical research (16). In the nonpregnant population, cellular-enabled blood glucose monitors that transmit results in real time to a health care provider (HCP) have improved both glycemic control and patient satisfaction in the self-management of diabetes (17,18). Translating these successes into novel solutions for pregnant women with diabetes could help to achieve the ultimate goals shared by patients and their care: positive maternal and neonatal outcomes.Here, we focus on mobile health (mHealth) apps and their applicability to the management of diabetes in pregnancy. We describe some of the core considerations when evaluating an app for use in patient care, discuss a number of apps developed specifically for diabetes self-management during pregnancy, and summarize key findings from the literature.     

Comparison of Two Electronic Systems for Obtaining Diabetes Care Indicators in Clinical Practice

We compared the completeness of data captured by physicians in a diabetes outpatient clinic using a general electronic health record system versus one that was specifically geared to diabetes. Use of a diabetes-oriented data system was found to allow for greater capture of crucial variables required for diabetes care than a general electronic record and was well accepted by health care providers.

Treatment in patients living with type 2 diabetes requires multicomponent and patient-focused medical care. However, barriers, including costs, inadequate care, lack of access to the health care system, and difficulty obtaining complete medical records, pose challenges in the management of these patients (1,2). Health care technologies offer many potential benefits, including improved efficiency, improved quality of care, reduced costs, and control in terms of expanded treatment options. Furthermore, health technologies can offer patients more access to their own health status and records (3,4).Since the implementation of electronic health record (EHR) systems, multiple studies have evaluated the utility of these electronic tools and their benefits in terms of patients’ health (4). EHR systems have led to care improvements in critical clinical domains and promote adherence to recommendations for optimum diabetes management of diabetes, for which the regular assessment of blood glucose, blood pressure, and lipid levels, as well as provision of appropriate foot and eye care, are essential (5–7). Diabetes care has been found to improve significantly in response to a multicomponent intervention involving a database-linked EHR system; receiving adequate medical care reduced cardiovascular mortality by 30%, blindness by 90%, and end-stage renal disease by 50% (8).Possible factors related to the improvement in diabetes care associated with EHR systems are the implementation of indicators or reminders within these systems that allow clinicians to easily see when biochemical studies should be performed (e.g., A1C, lipid, and microalbuminuria measurements), foot and retinal examinations should be scheduled, and evidence-based goals should be set or reviewed. Also, EHR systems have been found to promote the capture of essential information, with recording up to 84.8% of the total A1C values, 98.5% of systolic blood pressure readings, and 70.6% of LDL cholesterol values (8).EHR systems specifically designed to improve diabetes care are not routinely used in clinical practice, especially in developing countries where the use of traditional health records is common. Implementing such an EHR system could benefit patients, health care professionals (HCPs), and health systems and provide HCPs with information to improve the quality of care they deliver. This study aimed to compare the data captured by the physicians of a diabetes outpatient clinic using a general EHR system versus a diabetes-oriented EHR system called (in Spanish) Sistema de Monitoreo Integral en Diabetes (SMID). Researchers evaluated the percentage of missing data in each system and HCP acceptance of the diabetes-oriented system.