Acceptability of data linkage to identify women at risk of postnatal complication for the development of digital risk prediction tools and interventions to better optimise postnatal care, a qualitative descriptive study design.

BACKGROUND: Pregnancy acts as a cardiovascular stress test. Although many complications resolve following birth, women with hypertensive disorder of pregnancy have an increased risk of developing cardiovascular disease (CVD) long-term. Monitoring postnatal health can reduce this risk but requires better methods to identity high-risk women for timely interventions. METHODS: Employing a qualitative descriptive study design, focus groups and/or interviews were conducted, separately engaging public contributors and clinical professionals. Diverse participants were recruited through social media convenience sampling. Semi-structured, facilitator-led discussions explored perspectives of current postnatal assessment and attitudes towards linking patient electronic healthcare data to develop digital tools for identifying postpartum women at risk of CVD. Participant perspectives were gathered using post-it notes or a facilitator scribe and analysed thematically. RESULTS: From 27 public and seven clinical contributors, five themes regarding postnatal check expectations versus reality were developed, including 'limited resources', 'low maternal health priority', 'lack of knowledge', 'ineffective systems' and 'new mum syndrome'. Despite some concerns, all supported data linkage to identify women postnatally, targeting intervention to those at greater risk of CVD. Participants outlined potential benefits of digitalisation and risk prediction, highlighting design and communication needs for diverse communities. CONCLUSIONS: Current health system constraints in England contribute to suboptimal postnatal care. Integrating data linkage and improving education on data and digital tools for maternal healthcare shows promise for enhanced monitoring and improved future health. Recognised for streamlining processes and risk prediction, digital tools may enable more person-centred care plans, addressing the gaps in current postnatal care practice.

Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.

PURPOSE: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality. METHODS: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models. RESULTS: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time. CONCLUSION: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.

Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100 years using linked English primary care and hospital data.

BACKGROUND: Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes. METHODS: This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines). CONCLUSIONS AND RELEVANCE: There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.

Esterase and ALDH dehydrogenase-based pesticide degradation by Bacillus brevis 1B from a contaminated environment.

The isolated bacterial strain (Bacillus brevis strain 1 B) showed a maximum tolerated level of 450 mg L-1 of the selected pesticides namely: imidacloprid, fipronil, cypermethrin, and sulfosulfuron. Within 15 days of the experiment, strain 1 B was able to reduce up to 95% of a pesticide mixture (20 mg L-1) in a carbon-deficient medium (minimal medium). The optimal conditions obtained using Response Surface Methodology (RSM) were: inoculums; 2.0 × 107 CFU mL-1, shaking speed; 120 rpm, and pesticide concentration; 80 mg L-1. After 15 days of soil-based bioremediation using strain 1 B, the degradation pattern for imidacloprid, fipronil, cypermethrin, sulfosulfuron, and control was 99, 98.5, 94, 91.67, and 7%, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was used to determine the intermediate metabolites of cypermethrin with bacterial 1 B as 2-cyclopenten-1-one, 2-methylpyrrolidine, 2-oxonanone, 2-pentenoic acid, 2-penten-1-ol, hexadecanoic acid or palmitic acid, pentadecanoic acid, 3-cyclopentylpropionic acid, and 2-dimethyl. Furthermore, genes encoding aldehyde dehydrogenase (ALDH) and esterase were expressed under stress conditions and connected to pesticide bioremediation. Hence the efficacy of Bacillus brevis (1 B) could be employed for the bioremediation of pesticide mixtures and other toxic substances (dye, polyaromatic hydrocarbon, etc.) from contaminated sites.

Preventing Risks of Infections and Medication Errors in IV therapy (PRIME): a patient safety initiative.

BACKGROUND: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these. METHODS: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted. RESULTS: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management. CONCLUSION: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

Indigenous bacterial consortium-mediated cypermethrin degradation in the presence of organic amendments and Zea mays plants.

Cypermethrin is a toxic pyrethroid insecticide that is widely used in agricultural and household activities. One of the most serious issues is its persistence in the environment, because it is easily transported to the soil and aquatic ecosystem. The biodegradation of cypermethrin is emerging as an environmentally friendly method for large-scale treatment. This study examined the application of a novel binary bacterial combination-based (Bacillus thuringiensis strain SG4 and Bacillus sp. strain SG2) approach used for the enhanced degradation of cypermethrin from the environment. The bacterial strains degraded cypermethrin (80% and 85%) in the presence of external nitrogen sources (KNO3 and NaNO3). Furthermore, when immobilized in agar disc beads, the co-culture degraded cypermethrin (91.3%) with a half-life (t1/2) of 4.3 days compared to 4.9 days using sodium alginate beads. Cereal straw, farmyard manure, press mud compost, fresh cow dung, and gypsum were used as organic amendments in the soil to stimulate cypermethrin degradation. Cereal straw promoted the fastest cypermethrin degradation among the different organic amendments tested, with a t1/2 of 4.4 days. The impact of cypermethrin-degrading bacterial consortium on cypermethrin rhizoremediation was also investigated. Bacterial inoculums exhibited beneficial effects on plant biomass. Moreover, Zea mays and the bacterial partnership substantially enhanced cypermethrin degradation in soil. Six intermediate metabolites were detected during the degradation of cypermethrin, indicating that cypermethrin could be degraded first by the hydrolysis of its carboxyl ester bond, followed by the cleavage of the diaryl linkage and subsequent metabolism. Our findings highlight the promising potential and advantages of the bacterial consortium for the bioremediation of a cypermethrin-contaminated environment.

Novel mechanism and degradation kinetics of pesticides mixture using Bacillus sp. strain 3C in contaminated sites.

The present study has investigated the potential of Bacillus sp. strain 3C able to degrade mixture of pesticides from the environment. It showed maximum tolerance up to 450 mg·L-1 for cypermethrin, fipronil, imidacloprid and sulfosulfuron. The strain 3C was able to degrade up to the 94% of mixture of pesticides (20 mg·L-1) within 15 days of experiment. The Box-Behnken design of Response Surface Methodology (RSM) determined the optimized conditions as; inoculum size 3.0 × 107 CFU·mL-1, shaking speed 120 rpm, and pesticides concentration 80 mg·L-1. In soil-based bioremediation with strain 3C after 15 days degradation pattern was; 99, 94, 92, 92 and 7% for the imidacloprid, sulfosulfuron, fipronil, cypermethrin and control respectively. The novel intermediate metabolites for cypermethrin degradation were investigated as decyl isobutyl ester, phthalic acid, cyclopropane carboxylic acid tri dec-2-ynyl ester, 9- octadecanal, tridecane, propanoic acid, cyclohexene, bicyclo[2.2.1] heptan-2-ol, and acetic acid were identified using Gas chromatography Mass Spectrometry (GC-MS) with strain 3C. Moreover, the results of the laccase based enzymatic kinetics suggested that the rate of production was maximum in pesticides stress (94 µg·µL-1) whereas, in normal condition 51 µg·µL-1. The Km value found to be decreased in pesticides stress condition 12.25 and increment in Km 13.58 mM was observed without stress. Furthermore, aldehyde dehydrogenase (ALDH) and laccase encoding genes were amplified and linked with mixture of pesticides bioremediation. The efficiency of bacterial strain 3C, could be used for bioremediation of mixture of pesticides, and other xenobiotic compounds from the contaminated environments.

Evaluation of a novel sputum processing ReaSLR methodology for improving sensitivity of smear microscopy in clinical samples.

Background: Early case detection is a crucial step in the control of tuberculosis (TB). Sputum smear microscopy is the primary method of TB diagnosis in developing countries. The modified Petroff's method using sodium hydroxide at concentrations ranging between 2% and 4% to digest the specimen is widely used in developing countries. A novel ReaSLR (ReaMetrix's Sputum Liquefying Reagent) methodology has been proposed as a simple, easy, low-cost, and better alternative to conventional methods for sputum processing. This study was undertaken to evaluate the performance of the ReaSLR method of sputum processing in comparison with that of the modified Petroff's method. Methods: Early-morning sputum samples were collected. After preparing a direct smear, each sample was divided into two equal halves and processed by both the methods, i.e., modified Petroff's method and ReaSLR method. Direct smears were graded according to Revised National Tuberculosis Control Program grading, and smears prepared after processing by the two different methods were graded according to Center for Disease Control and Prevention grading. Smear microscopy results were compared taking culture results of samples processed by the modified Petroff's method as the gold standard. Results: The rate of smear positivity with the modified Petroff's method (22.22%) was found to be higher than that with direct smear microscopy (13.56%; p = 0.0002) and the ReaSLR method (17.32%; p = 0.04). The modified Petroff's method was found to be 26.76% more sensitive than direct microscopy and 15.59% more sensitive than the ReaSLR method. Conclusion: The ReaSLR method was not superior to the modified Petroff's method for smear microscopy. Although this method was more sensitive than the direct method in smear microscopy, the modified Petroff's method performed much better than the ReaSLR method.

Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics.

How to cite this article: Khilnani GC, Tiwari P, Zirpe KG, Chaudhary D, Govil D, Dixit S, et al. Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics. Indian J Crit Care Med 2022;26(S2):S77-S94.

Impact of nanophos in agriculture to improve functional bacterial community and crop productivity.

BACKGROUND: Since the World's population is increasing, it's critical to boost agricultural productivity to meet the rising demand for food and reduce poverty. Fertilizers are widely used in traditional agricultural methods to improve crop yield, but they have a number of negative environmental consequences such as nutrient losses, decrease fertility and polluted water and air. Researchers have been focusing on alternative crop fertilizers mechanisms to address these issues in recent years and nanobiofertilizers have frequently been suggested. "Nanophos" is a biofertilizer and contains phosphate-solubilising bacteria that solubilises insoluble phosphate and makes it available to the plants for improved growth and productivity as well as maintain soil health. This study evaluated the impact of nanophos on the growth and development of maize plants and its rhizospheric microbial community such as NPK solubilising microbes, soil enzyme activities and soil protein under field condition after 20, 40 and 60 days in randomized block design. RESULTS: Maize seeds treated with nanophos showed improvement in germination of seeds, plant height, number of leaves, photosynthetic pigments, total sugar and protein level over control. A higher activity of phenol, flavonoid, antioxidant activities and yield were noticed in nanophos treated plants over control. Positive shift in total bacterial count, nitrogen fixing bacteria, phosphate and potassium solubilizers were observed in the presence of nanophos as compared to control. Soil enzyme activities were significantly (P < 0.05) improved in treated soil and showed moderately correlation between treatments estimated using Spearman rank correlation test. Real time PCR and total soil protein content analysis showed enhanced microbial population in nanophos treated soil. Obtained results showed that nanophos improved the soil microbial population and thus improved the plant growth and productivity. CONCLUSION: The study concluded a stimulating effect of nanophos on Zea mays health and productivity and indicates good response towards total bacterial, NPK solubilising bacteria, soil enzymes, soil protein which equally showed positive response towards soil nutrient status. It can be a potential way to boost soil nutrient use efficiency and can be a better alternative to fertilizers used in the agriculture.

Biotechnological basis of microbial consortia for the removal of pesticides from the environment.

The application of microbial strains as axenic cultures has frequently been employed in a diverse range of sectors. In the natural environment, microbes exist as multispecies and perform better than monocultures. Cell signaling and communication pathways play a key role in engineering microbial consortia, because in a consortium, the microorganisms communicate via diffusible signal molecules. Mixed microbial cultures have gained little attention due to the lack of proper knowledge about their interactions with each other. Some ideas have been proposed to deal with and study various microbes when they live together as a community, for biotechnological application purposes. In natural environments, microbes can possess unique metabolic features. Therefore, microbial consortia divide the metabolic burden among strains in the group and robustly perform pesticide degradation. Synthetic microbial consortia can perform the desired functions at naturally contaminated sites. Therefore, in this article, special attention is paid to the microbial consortia and their function in the natural environment. This review comprehensively discusses the recent applications of microbial consortia in pesticide degradation and environmental bioremediation. Moreover, the future directions of synthetic consortia have been explored. The review also explores the future perspectives and new platforms for these approaches, besides highlighting the practical understanding of the scientific information behind consortia.

Effects of primary care C-reactive protein point-of-care testing on antibiotic prescribing by general practice staff: pragmatic randomised controlled trial, England, 2016 and 2017.

BackgroundC-reactive protein (CRP) testing can be used as a point-of-care test (POCT) to guide antibiotic use for acute cough.AimWe wanted to determine feasibility and effect of introducing CRP POCT in general practices in an area with high antibiotic prescribing for patients with acute cough and to evaluate patients' views of the test.MethodsWe used a McNulty-Zelen cluster pragmatic randomised controlled trial design in general practices in Northern England. Eight intervention practices accepted CRP testing and eight control practices maintained usual practice. Data collection included process evaluation, patient questionnaires, practice audit and antibiotic prescribing data.ResultsEight practices with over 47,000 patient population undertook 268 CRP tests over 6 months: 78% of patients had a CRP < 20 mg/L, 20% CRP 20-100 mg/L and 2% CRP > 100 mg/L, where 90%, 22% and 100%, respectively, followed National Institute for Health and Care Excellence (NICE) antibiotic prescribing guidance. Patients reported that CRP testing was comfortable (88%), convenient (84%), useful (92%) and explained well (85%). Patients believed CRP POCT aided clinical diagnosis, provided quick results and reduced unnecessary antibiotic use. Intervention practices had an estimated 21% reduction (95% confidence interval: 0.46-1.35) in the odds of prescribing for cough compared with the controls, a non-significant but clinically relevant reduction.ConclusionsIn routine general practice, CRP POCT use was variable. Non-significant reductions in antibiotic prescribing may reflect small sample size due to non-use of tests. While CRP POCT may be useful, primary care staff need clearer CRP guidance and action planning according to NICE guidance.

Chemical profiling, cytotoxicity and phytotoxicity of foliar volatiles of Hyptis suaveolens.

In the present study, the essential oil (EO) of Hyptis suaveolens has been explored for the first time for its phytotoxic and cytotoxic activities. The phytotoxic activity was assessed against rice (Oryza sativa) and its major troublesome weed, Echinochloa crus-galli, under laboratory and screenhouse conditions. GC-MS analysis revealed EO to be monoterpenoid (~ 79% monoterpenes) in nature with α-phellandrene (22.8%), α-pinene (10.1%) and limonene (8.5%) as the major chemical constituents. The laboratory bioassay showed a complete growth inhibitory effect of EO (≥ 2 mg mL-1) towards the germination and seedling growth of E. crus-galli. However, the inhibitory effect on rice was much less (~40% inhibition). EO caused visible injury, reduction in chlorophyll content, cell viability and ultimately led to complete wilting of E. crus-galli plants. In addition, EO altered the cell division in the meristematic cells of Allium cepa as depicted by ~63% decrease in mitotic index. EO exposure induced several aberrations at chromosomal (c-mitosis, anaphase bridges, chromosomal breakage, vagrant chromosomes, and sticky chromosomes) and cytological level (cytoplasm destruction, peripheral nuclei, and bi-nucleate cells). The present study concludes that H. suaveolens EO possesses phytotoxic activity due to its mito-depressive activity, and could serve as a natural herbicide under sustainable agricultural practices.

Professional responsibilities reported by pharmacists completing residencies in community-based settings.

OBJECTIVES: To evaluate the professional responsibilities of pharmacists who completed residencies in a community-based setting and to determine if there is a difference in responsibilities for pharmacists completing different types of PGY-1 residency and PGY-2 residency training. METHODS: A survey was designed by adapting questions from the 2014 Pharmacist Workforce Survey and creating other questions designed for this project. Surveys were distributed electronically to residency program directors of PGY-1 community-based pharmacy residencies, PGY-1 pharmacy residencies in ambulatory care environments, and PGY-2 ambulatory care residencies; program directors were asked to distribute the survey to all residency alumni of their program. RESULTS: A total of 450 programs were identified; 349 responses were received, with respondents having completed residency training from 1989 to 2016. Respondents represented at least 73 different residency programs across the country. More than 97% of respondents agreed or strongly agreed that their residency training prepared them to be successful in their career. Nondispensing patient care, ranging from 39.0% to 52.5%, represented the largest percentage of job responsibilities. Current job responsibilities contained a higher percentage of business or organization management compared with first job (17.7% vs. 5.8%; P < 0.001). CONCLUSION: Pharmacists completing residency training have a large percentage of their first jobs associated with patient care responsibilities, regardless of the type of training received or the type of setting.

Enhancing hospital care of patients with cognitive impairment.

Purpose The patient-centred management of people with cognitive impairment admitted to acute health care facilities can be challenging. The TOP5 intervention utilises carers' expert biographical and social knowledge of the patient to facilitate personalised care. The purpose of this paper is to explore whether involvement of carers in the TOP5 initiative could improve patient care and healthcare delivery. Design/methodology/approach A small-scale longitudinal study was undertaken in two wards of one acute teaching hospital. The wards admitted patients with cognitive impairment, aged 70 years and over, under geriatrician care. Data for patient falls, allocation of one-on-one nurses ("specials"), and length-of-stay (LOS) over 38 months, including baseline, pilot, and establishment phases, were analysed. Surveys of carers and nursing staff were undertaken. Findings There was a significant reduction in number of falls and number of patients allocated "specials" over the study period, but no statistically significant reduction in LOS. A downward trend in complaints related to communication issues was identified. All carers ( n=43) completing the feedback survey were satisfied or very satisfied that staff supported their role as information provider. Most carers (90 per cent) felt that the initiative had a positive impact and 80 per cent felt that their loved one benefitted. Six months after implementation of the initiative, 80 per cent of nurses agreed or strongly agreed that it was now easier to relate to carers of patients with cognitive impairment. At nine-ten months, this increased to 100 per cent. Originality/value Actively engaging carers in management of people with cognitive impairment may improve the patient, staff, and carer journeys, and may improve outcomes for patient care and service delivery.

Retrospective Evaluation of Patients Who Leave against Medical Advice in a Tertiary Teaching Care Institute.

CONTEXT: Discharge against medical advice or leave against medical advice (DAMA or LAMA) is a global phenomenon. The magnitude of LAMA phenomenon has a wide geographical variation. LAMA reasons are an area of concern for all involved in health-care delivery system. AIMS AND OBJECTIVES: The study aimed to evaluate cases of LAMA retrospectively in a tertiary teaching care institute (1) to find the magnitude of LAMA cases (2) to evaluate demographic and patient characteristics of these cases. SUBJECTS AND METHODS: We screened hospital record of a referral institute over 1 year after approval from IEC and ICMR, New Delhi. Patient demographics and disease characteristics were noted and statistically analyzed after compilation. RESULTS: A total of 47,583 patients were admitted in the year 2015 through emergency and outpatient department. One thousand five hundred and fifty-six (3.3%) patients got DAMA. The mean age of patient excluding infants was 46.64 ± 20.55 years. There were 62.9% of males. Average hospital stay of these cases was 4.09 ± 4.39 days. Most of the patients (70%) belonged to medical specialties and had longer stay as compared to surgical specialties. Most of LAMA patients were suffering from infections, trauma, and malignancies. Most of the patients had LAMA from ward (62%) followed by Intensive Care Unit (ICU) (28.8%) and emergency (9.2%). In 592 (38%) of LAMA patients, the reason for leaving was not clear. The common cited reasons for LAMA were financial (27.6%) and poor prognosis (20.5%). CONCLUSIONS: About 3.3% of patients left hospital against medical advice in our retrospective analysis. Most of these cases did so from ward followed by ICU. Financial reasons and expected poor outcome played a significant role.

The oral health status of older patients in acute care on admission and Day 7 in two Australian hospitals.

Objective: to determine the oral health status of older patients in acute care wards at admission and after 7 days. Methods: a prospective descriptive study was conducted in two acute tertiary referral hospitals in New South Wales, Australia. Oral health was assessed on admission (within 24 h) and Day 7 using the Oral Health Assessment Tool. Results: a total of 575 patients were admitted under the Geriatric teams at the two hospitals. Four hundred and thirty-five (76%) patients had oral cleanliness (debris) scores in the 'not healthy' range with food particles, tartar or plaque evident in at least one area in most areas of the mouth, teeth or dentures. At Day 7 206 were reassessed. One hundred and forty-nine patients (73%) were in the 'not healthy' range and of these 127 (62%) had the same score as on admission. Conclusion: poor oral health is common in older people admitted to hospital acute care wards and does not improve over a 7-day period. Given the link between oral health and general health the next steps are to determine how oral health can be improved in this setting and see whether this leads to better patient outcomes.

Scrub typhus in Uttarakhand & adjoining Uttar Pradesh: Seasonality, clinical presentations & predictors of mortality.

BACKGROUND & OBJECTIVES: Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India. METHODS: Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA. RESULTS: A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death. INTERPRETATION & CONCLUSIONS: The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity.

BACKGROUND: Cardio-Oncology is an evolving discipline that focuses on the management of cancer patients who develop cardiovascular complications as a result of their treatment. Although the current combination of surgical resection, radiation, and chemotherapy may lead to a cure in cancer patients, the administration of anti-cancer drugs, in particular Doxorubicin (DOX) and Trastuzumab (TRZ), is associated with an increased risk of cardiotoxicity. Little is known on the potential cardioprotective role of renin angiotensin system (RAS) antagonists in the prevention of DOX+TRZ mediated cardiotoxicity. OBJECTIVE: The aim of the study was to determine whether RAS antagonists would be useful in attenuating DOX+TRZ induced cardiotoxicity. METHODS: A total of 240 C57Bl/6 mice were randomized to prophylactic treatment with placebo, Aliskiren, Perindopril, or Valsartan for a total of 13 weeks. Within each arm, mice received treatment with either DOX, TRZ, or the combination of both drugs. Serial murine echocardiography was performed weekly to characterize the degree of cardiovascular remodeling within each group. RESULTS: In wild-type (WT) mice treated with DOX+TRZ, LV end diastolic internal diameter (LVID) increased from 3.1 ± 0.2 mm at baseline to 4.6 ± 0.3 mm at week 13 (p < 0.05) and the LV fractional shortening (FS) decreased from 52 ± 2% at baseline to 26 ± 2% at week 13 (p < 0.05). Prophylactic treatment with Aliskiren, Perindopril, or Valsartan attenuated the degree of LV cavity dilatation with LVID dimensions of 3.9 ± 0.2 mm, 4.1 ± 0.2 mm, and 4.2 ± 0.1 mm at week 13, respectively (p < 0.05). Similarly, prophylactic treatment with Aliskiren, Perindopril, or Valsartan was partially cardioprotective with FS of 40 ± 1%, 32 ± 1%, and 33 ± 2% at week 13, respectively (p < 0.05). As compared to WT mice receiving DOX+TRZ, prophylactic treatment with RAS inhibition was also associated with improved survival, corroborating the echocardiographic findings. CONCLUSION: The cardiotoxic effects of DOX+TRZ were partially attenuated by the prophylactic administration of RAS antagonists in a chronic murine model of chemotherapy induced cardiac dysfunction.