PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis. Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed. Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy. Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

Multi-location evaluation of field pea in Indian climates: eco-phenological dynamics, crop-environment relationships, and identification of mega-environments.

Characterization of crop-growing environments in relation to crop's genotypic performance is crucial to harness positive genotype-by-environment interactions (GEI) in systematic breeding programs. Given that, the study aimed to delineate the impact of diverse environments on crop phenology and yield traits of dwarf-statured field pea, pinpointing location(s) favoring higher yield and distinctiveness within breeding lines. We tested twelve field pea breeding lines across twenty locations in India, covering Central Zone (CZ), North Western Plain Zone (NWPZ), North Eastern Plain Zone (NEPZ), and Northern Hill Zone (NHZ). Across these locations, maximum and minimum temperatures during flowering (TMAXF, TMINF) and reproductive period (TMAXRP, TMINRP) ranged 18.9-28.3, 3.3-18.0, 15.0-30.8, and 7.9-22.1oC, respectively. Meanwhile, notable variations in phenological and agronomic traits (coefficient of variation) were observed: flowering (31%), days to maturity (21%), reproductive period (18%), grain yield (48%), and 100-seed weight (18%). Combined ANOVA demonstrated an oversized impact of environment (81%) on yield, while genotype and GEI effects were 2% and 14%, respectively. The variables TMINF, TMINRP, and cumulative growing degree-day showed positive correlations with yield, while extended vegetative and maturity durations negatively influenced yield (p < 0.05). Additionally, linear mixed-models and PCA results explained that instability in crop phenology had significant influence on field pea yield. Seed weight was markedly varied within the locations (9.9-20.8 g) and both higher and lower seed weights were associated with lower yields (Optimal = 17.1 g). HA-GGE biplot-based on environment focus-scaling demonstrated three mega-environments and specific locations viz. Kota (CZ), SK Nagar (CZ), Raipur (CZ), Sehore (CZ), and Pantnagar (NWPZ) as the ideal testing-environments with high efficiency in selecting new genotypes with wider adaptability. The study findings highlight distinct impact of environments on crop phenology and agronomic traits of field pea (dwarf-type), hold substantial value in designing efficient field pea (dwarf-type) breeding program at mega-environment scale.

Comparison of the Efficacy of Macintosh Laryngoscope Versus Airtraq Videolaryngoscope for Visualization of Laryngeal Structures at the End of Thyroidectomy: A Randomized Control Study.

To compare the efficacy of conventional Macintosh laryngoscope with Airtraq videolaryngoscope for visualization of laryngeal structures to rule out recurrent laryngeal nerve injury at the end of thyroidectomy. This randomized double-blind control study was conducted following IEC-Human approval, prospective CTRI registration and written informed consent from participants. Patients of either sex, aged 18-65 years, ASA grade I/II, scheduled for thyroidectomy under GA were included. Group DL underwent direct laryngoscopy using Macintosh blade whereas group VL underwent laryngoscopy using Airtraq® videolaryngoscope. CL(Cormack-Lehane) grade of laryngeal view, time taken to achieve optimal view, haemodynamic parameters, Patient reactivity score(PRS) and complications were noted. Unpaired t-test, chi-square test were used. A total of 73 patients were included for study with 38 in group DL and 35 in group VL. The grade of laryngeal view was found to be significantly better with Airtraq® VL compared to Macintosh laryngoscope without the application of BURP (p < 0.05). In the DL group, 34.2% (n = 13) had a CL grade I, 36.8% (n = 14) had CL grade 2A, 13.2% had CL grade 2B (n = 5) and 15.8% (n = 6) had CL Grade 3 at the end of thyroidectomy. On the contrary, in the VL Group, 71.5% (n = 25) of the participants had a CL Grade I; whereas, 20% (n = 7) had a CL Grade 2A, 5.7% (n = 2) had CL grade 2B and 2.8% (n = 1) of participants had CL grade 3. The mean "time taken to achieve optimal view' was comparable between the two groups (DL = 39.16 ± 105.53 s vs. VL = 38.89 ± 20.69 s) (p = 0.988).The haemodynamic parameters, Patient reactivity score and complications were comparable between the two groups. The performance of Airtraq® videolaryngoscope, a channelled VL is better than conventional Macintosh laryngoscope in terms of the optimal glottic view obtained to rule out recurrent laryngeal nerve palsy at the end of thyroidectomy.

Analgesic efficacy of Clonidine as an adjuvant in ultrasound-guided rectus sheath block for midline incisional hernia repair - A randomized double-blind controlled trial.

Background and Aims: Clonidine as an adjuvant has not been evaluated in rectus sheath block (RSB) for postoperative pain management in incisional hernia repair. The study aims to evaluate clonidine as an adjuvant in single-shot RSB along with general anesthesia (GA). Material and Methods: This randomized, double-blind controlled study was conducted following IEC-Human approval and written informed consent from 30 patients of either sex, aged 16 to 60 years, ASA physical status I or II undergoing midline incisional hernia repair under GA. All patients received ultrasound-guided bilateral RSB following administration of GA. The subjects enrolled in the study were randomly allocated to receive either normal saline 1 mL (group B) or clonidine 1 µg/kg diluted to 1 mL with normal saline (group BC) as adjuvant along with 9 mL bupivacaine hydrochloride 0.25%. Inj. tramadol 1 mg/kg was administered for rescue analgesia. The primary outcome was the time to first request for analgesia, and secondary outcomes were total consumption of rescue analgesic over 24 h, numerical rating score (NRS), patients' satisfaction, hemodynamics, and side effects. Unpaired t-test and Chi-square test were used. Results: On intergroup analysis, the mean time to first request for analgesia (in min) was significantly higher in group BC i.e., [9.60 (± 5.23) vs 5.33 (± 3.53); (P < 0.034]; whereas, the mean rescue analgesic consumption in 24 h (in mg) was higher in group B i.e., [(88.00 ± 60.97) vs (46.00 ± 48.08)]; (P < 0.045)]. Hemodynamic parameters i.e., mean blood pressure and heart rate were comparable between the two groups, and there were no side effects. Conclusion: Clonidine as an adjuvant in single-shot ultasonography (USG)-guided RSB along with GA is efficacious for postoperative pain management following midline incisional hernia repair.

Trends of syphilis seroprevalence at a tertiary care center in New Delhi, India: A 10-year analysis.

Objectives: Syphilis has been called the great mimicker or the great imitator due to its myriad of clinical presentations. Despite strenuous concerted efforts toward the elimination of syphilis, it still remains a goal to be achieved. During recent years, many different trends of syphilis have been reported from around the globe. Methods: A retrospective observational clinico-investigative study was carried out to analyze the 10-year trends of syphilis at one of the largest public sector hospitals in India. Results and Conclusion: Both venereal disease research laboratory and Treponema pallidum Hemagglutination assay positivity rates showed a significant declining trend from 2007 to 2016, reflecting the success of the National Sexually Transmitted Infection Prevention and Control Program.

Retention of Knowledge and Efficacy of a Hands-on Training Session in Oxygen Therapy for COVID-19 among Healthcare Workers.

Introduction: We conducted basic hands-on training in oxygen therapy and ventilatory management of coronavirus disease-2019 (COVID-19) patients to health care workers (HCWs) at our tertiary care hospital. We designed this study aiming to find out the impact of hands-on training in oxygen therapy for COVID-19 patients on the knowledge and degree of retention of this gained knowledge 6 weeks after the training session among HCWs. Materials and methods: The study was conducted after obtaining approval from the Institutional Ethics Committee. A structured questionnaire consisting of 15 multiple-choice questions was given to the individual HCW. This was followed by a structured 1-hour training session on "Oxygen therapy in COVID-19", following which the same questionnaire was given to the HCWs with the questions in a different order. After 6 weeks, the same questionnaire with questions in a different format was sent to the participants as a Google form. Results: A total of 256 responses were obtained for the pre-training test and post-training test. The median [IQR] pre-training test scores and post-training test scores were 8 [7-10] and 12 [10-13], respectively. The median retention score was 11 [9-12]. The retention scores were significantly higher than the pre-test scores. Conclusion: About 89% of the HCWs had a significant gain of knowledge. About 76% of the HCWs were able to retain knowledge, which also means the training program was successful. A definitive improvement in baseline knowledge was observed after 6 weeks of training. We propose conducting reinforcement training after 6 weeks of primary training to further augment retention. How to cite this article: Singh A, Salhotra R, Bajaj M, Saxena AK, Sharma SK, Singh D, et al. Retention of Knowledge and Efficacy of a Hands-on Training Session in Oxygen Therapy for COVID-19 among Healthcare Workers. Indian J Crit Care Med 2023;27(2):127-131.

Modulation of mTORC1 and IL-6 following mirror therapy and pregabalin in complex regional pain syndrome type 1.

Aim: The study was designed to evaluate the modulation of mTOR complex 1 (mTORC1) and IL-6 genes following the use of mirror therapy (MT) and pregabalin in complex regional pain syndrome type-1 patients. Materials & methods: Two groups of 20 patients: MT group received MT and pregabalin, control therapy group received pregabalin. Neuropathic pain symptom inventory (NPSI), numeric rating scale - pain, modified motor activity log, SF-12 questionnaire for quality of life and IL-6 and mTORC1 expression were evaluated. Results: Group MT demonstrated a statistically significant improvement in NPSI burning, NPSI allodynia and numeric rating scale pain scores, modified motor activity log and SF-12 scores. Significant downregulation of mTORC1 and IL-6 observed in both. Conclusion: MT is a significant adjunct to pregabalin in improving motor function, quality of life and alleviating pain in complex regional pain syndrome type 1. Clinical Trial Registration: CTRI/2019/01/017272 (ClinicalTrials.gov).

Complex regional pain syndrome is a form of long-term pain that involves an arm or a leg. It can develop after an injury, a surgery or a stroke. Although many drugs have been used for its treatment, the limited relief that these drugs produce along with their side effects have shifted focus to other physical and psychological modes of therapy. Mirror therapy is one such modality where the image of normal functioning limb seen in a mirror placed over the affected limb leads to pain relief in the affected limb. We have provided evidence that mirror therapy can reduce the pain of this syndrome and also decrease the levels of pain related genes in the body. This will help us to devise better treatment strategies for complex regional pain syndrome.

Haemodynamic predisposition to acute kidney injury: Shadow and light!

Acute kidney injury (AKI) could well be regarded as a sentinel complication given it is relatively common and associated with a substantial risk of subsequent morbidity and mortality. On the aegis of 'prevention is better than cure', there has been a wide interest in evaluating haemodynamic predisposition to AKI so as to provide a favourable renoprotective haemodynamic milieu to the subset of patients presenting a significant risk of developing AKI. In this context, the last decade has witnessed a series of evaluation of the hypotension value and duration cut-offs associated with risk of AKI across diverse non-operative and operative settings. Nevertheless, a holistic comprehension of the haemodynamic predisposition to AKI has been a laggard with only few reports highlighting the potential of elevated central venous pressure, intra-abdominal hypertension and high mean airway pressures in considerably attenuating the effective renal perfusion, particularly in scenarios where kidneys are highly sensitive to any untoward elevation in the afterload. Despite the inherent autoregulatory mechanisms, the effective renal perfusion pressure (RPP) can be modulated by a number of haemodynamic factors in addition to mean arterial pressure (MAP) as the escalation of renal interstitial pressure, in particular hampers kidney perfusion which in itself is a dynamic interplay of a number of innate pressures. The present article aims to review the subject of haemodynamic predisposition to AKI centralising the focus on effective RPP (over and above the conventional 'tunnel-vision' for MAP) and discuss the relevant literature accumulating in this area of ever-growing clinical interest.

Development and implementation of a sustainable COVID-19 training package for healthcare workers: Experience from a teaching hospital of North India.

Background: With the impending threat of future COVID-19 waves, it is imperative that teaching hospitals develop, implement, and evaluate a systematic training program to render HCW elastic in delivering COVID-19 related services. We present our experience in developing, implementing, and evaluating a sustainable and scalable COVID-19 patient management training package for healthcare workers. Materials and Methods: A mixed-methods study design was used. Rapid assessment to understand the need of the trainees and identify the available resources was done followed by planning of the training module and its implementation. The program was evaluated for effectiveness and sustainability. Data analysis was done using descriptive statistics and qualitative data generated from open-ended questions in the feedback forms and the discussions were analyzed using rapid content analysis. Results: A total of 66.8% of the doctors and 18.9% of the nurses were trained by online synchronous mode while 55.0% of the nursing officers and 47.1% of the nursing orderlies and paramedical staff were trained in onsite skill development sessions. Need assessment identified that healthcare workers were ill-prepared to use medical devices such as Bipap machines, ventilators, and oxygen delivery devices. The participants mentioned that the multidisciplinary approach and video-based demonstrations facilitated their online learning while the incremental learning approach, easy-to-understand terminology and hands-on experience facilitated their onsite skill development sessions. Conclusion: The COVID-19 training package developed was multidisciplinary, effective, sustainable, and scalable in a resource-limited setting. We suggest that this model can be adapted by healthcare organizations to develop and implement such training packages for their healthcare workers.

Ultrasound-guided transversalis fascia plane block versus wound infiltration for both acute and chronic post-caesarean pain management - A randomised controlled trial.

Background and Aims: Ultrasound-guided transversalis fascia plane block (USG-guided TFPB) has recently been evaluated for post-caesarean acute pain management. We compared it with standard wound infiltration for both acute and chronic post-caesarean pain management. Methods: All patients undergoing caesarean section (CS) under subarachnoid block were included and randomised. Patients in group C received standard wound infiltration (20 ml of 0.375% ropivacaine) and group-T received bilateral USG-guided TFPB (20 ml of 0.375% ropivacaine) at the end of the surgery. Acute pain assessed using numeric rating scale (NRS), time to first request of analgesia and total rescue analgesic consumption in 24 hours. The incidence of chronic persistent post-surgical pain (CPSP), neuropathic pain component and quality of life (QoL) were assessed. Fisher's exact test, Chi-square test, unpaired Student's t-test and Mann-Whitney U test were used. Results: Sixty patients were included with 30 in each group. NRS score on rest at 6th and 24th hour and on active movement at 1st hour was significantly decreased in group T. The "time to first request of analgesia" was statistically higher in group T, that is, 10.77 ± 1.39 h versus 6.30 ± 1.60 h. Five (16.6%) and two (6.6%) patients in groups C and T, respectively, required rescue analgesia in first 24 hours. 30% (n = 6) and 10% (n = 2) patients in groups C and T, respectively, developed CPSP. The neuropathic pain component was significantly reduced and QoL was significantly improved in group T. Conclusion: TFPB is efficacious for management of both acute and chronic post-caesarean pain management.

Awake Prone-Positioning in Patients on Non-Invasive Ventilation for Management of SARS-CoV-2 Pneumonia: A Systematic Review.

INTRODUCTION: Patients with corona virus disease-19 (COVID-19)-induced acute hypoxemic respiratory failure (AHRF) are often on non-invasive ventilation (NIV) and use of awake prone positioning (PP) may pose concern in terms of feasibility, efficacy and side effects. This systematic review was undertaken to evaluate the feasibility and efficacy of awake PP along with NIV in them. MATERIALS AND METHODS: A systematic literature search was conducted from the inception of COVID-19 until 15 August 2021. Various factors including feasibility, interface used, outcome, efficacy, side effects and limitations in both intensive care unit (ICU) and Non-ICU setups were noted. RESULTS: A total of 12 original articles and six case series including 359 patients were involved. Out of it, 40% (n = 122) of patients were in ICU and 60% (n = 237) in Non-ICU areas. Four clinical studies and four case series including 114 patients had evaluated PP along with helmet continuous positive airway pressure (CPAP). All had found PP with helmet CPAP to be feasible and efficacious; however, only one study documented the sustained improvement in oxygenation i.e., 12 h after PP. CONCLUSIONS: The present systematic review observed moderate to serious risk of bias amongst the included studies along with heterogeneity in terms of varied respiratory support amongst patients. However, the use of awake PP in patients on NIV has been found to be feasible and efficacious with no adverse events.

Effect of convalescent plasma therapy on mortality in moderate-to-severely Ill COVID-19 patients.

INTRODUCTION: The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. METHODS: This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. RESULTS: Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. CONCLUSIONS: We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved.

Modulation of signal transduction gene expression following pulsed radiofrequency in dorsal root ganglia and pregabalin therapy.

Introduction: A randomized controlled study was conducted to assess modulation of signal transduction genes (PKA, PKC and ERK) following integrated multimodal approach encompassing pulsed radiofrequency treatment (PRF) of dorsal root ganglion and pregabalin in thoracic postherpetic neuralgia (PHN). Clinical variables such as pain intensity and quality of life were also explored. Material & methods: A total of 40 Patients of PHN were recruited. 20 patients randomly assigned to each of the two groups, group PP administered PRF with pregabalin and group SP administered pregabalin alone. Results: Significant downregulation of PKA and ERK observed in group PP at end of 10th week (p < 0.05). A significantly positive correlation demonstrated between Visual analog scale scores and signal transduction genes expression in PHN patients. Conclusion: Downregulation of all three signal transduction genes was observed following the integrated multimodal approach; however, significant downregulation was observed with PKA and ERK only. A positive correlation observed between signal transduction gene expression and visual analog scale scores signify their role in the pathogenesis of PHN.

People who had nerve pain after recovering from a herpes attack (postherpetic neuralgia) were treated with pulsed radiofrequency (PRF) treatment of the dorsal root ganglion, which involves stimulating a nerve cluster at the base of the spine with radio waves, along with oral pregabalin therapy, or with pregabalin alone. Certain pain genes such PKA, PKC and ERK were found to be suppressed after the combined treatment with PRF and pregabalin. The suppression of these genes was also associated with the self-reported pain scores of the participants in the study.

Does performance and operational superiority of point-of-care test make it the investigation of choice in confirming syphilis?

Background: According to the World Health Organization, 6 million cases of syphilis occur every year. Serological tests for syphilis form the mainstay of diagnosis for syphilis. We evaluated the performance of point-of-care test (POCT) against other specific treponemal test for confirming the diagnosis of syphilis. Materials and Methods: Does performance and operational superiority of POCT make it the investigation of choice in confirming syphilis? Retrospectively, data were analyzed of 599 serum samples from Apex Regional sexually transmitted disease centre, Safdarjung Hospital, New Delhi, received for testing by syphilis treponemal assays (both nontreponemal reactive and nonreactive). These samples underwent treponemal testing for syphilis by the Treponema pallidum hemagglutination (TPHA), fluorescent treponemal antibody absorption test (FTA-ABS), and POCT. Performance characteristics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and diagnostic accuracy), and operational characteristics of POCT and TPHA were evaluated against the gold standard FTA-ABS. Results: A total of 599 samples were evaluated, of which 61.76% were positive by FTA-ABS. On analysis, the sensitivity was 91.08% and 91.89%, specificity was 89.08% and 87.34%, PPV was 93.09% and 92.14%, NPV was 86.08% and 86.96%, and diagnostic accuracy was 90.32% and 90.15% for POCT and TPHA, respectively. The lower cost, shorter turnaround time, lesser infrastructure and workforce need, and easy availability make the POCT operationally superior to TPHA. Conclusion: Owing to its operational superiority and higher specificity POCT can replace TPHA for confirming the diagnosis of Syphilis. POCT are affordable, equipment free, have room temperature storage, and yield result within 15 minutes, enabling same day testing and treatment. It can be used in a resource limited setting, for community setup or even self-testing.

Awake Prone Positioning in the Management of COVID-19 Pneumonia: A Systematic Review.

Background: The aim was to investigate the efficacy of prone positioning (PP) in the management of coronavirus disease-2019 (COVID-19) pneumonia in various setups, with various modes of oxygen therapy and its optimal duration. Materials and methods: A systematic literature search was conducted from inception until May 15, 2021. Patients with a validated diagnosis of COVID-19 and receiving PP were included. Various factors, including intensive care unit (ICU) or non-ICU setup, mode of oxygen therapy, outcome, duration of proning, and limitations, were noted. Results: We retrieved 36 articles with a total of 1,385 patients for qualitative analysis. Out of 36 articles, there were 17 original articles, 09 case series, and 10 case reports. Out of 1,385 participants, 78.9% (n = 1,093) and 21.0% (n = 292) of patients were managed in ICU and non-ICU setup, respectively. Awake PP with high flow nasal cannula (HFNC) was found to be a promising technique; however, the result was inconclusive with helmet continuous positive airway pressure (CPAP). No study has evaluated the optimal duration of awake PP and the associated long-term outcomes. Conclusion: We encourage the use of early awake self-proning in the management of COVID19 disease. However, the evidence in terms of its use in non-ICU setup, the optimal duration of PP, and various oxygenation devices are insufficient, thereby mandating further well-designed multicentric studies to evaluate its efficacy as an adjunct in the management of COVID-19 pneumonia in context to the aforementioned factor. How to cite this article: Chilkoti GT, Mohta M, Saxena AK, Ahmad Z, Sharma CS. Awake Prone Positioning in the Management of COVID-19 Pneumonia: A Systematic Review. Indian J Crit Care Med 2021;25(8):896-905.

Cancer induced bone pain: current management and future perspectives.

Recent improvements in the therapeutic armamentarium of oncology by the addition of targeted and immunotherapeutic agents have led to an increase in the life expectancy of advanced-stage cancer patients. This has led to an increased number of patients presenting with bone metastasis and experiencing episodes of cancer-induced bone pain (CIBP). CIBP is a crippling, chronic, morbid state interfering significantly with the functional capacity and the quality of life (QoL). CIBP is characterized by a complex multifactorial pathophysiological mechanism involving tumor cells, bone cells, inflammatory microenvironment, and the neuronal tissue. It may not be possible to mitigate pain completely; therefore, the aim should be to reach the lowest possible level of pain that allows for an acceptable QoL to the patient. Multimodality approach of surgical, radiation, medical and behavioral techniques is thus recommended to manage CIBP. This review discusses the pathogenesis and pathophysiological mechanism accompanying bone metastasis and CIBP, currently approved therapies for the management of CIBP, and the future perspective.