Off-label psychopharmacological interventions for autism spectrum disorders: strategic pathways for clinicians.

The prevalence of autism spectrum disorder (ASD) continues to see a trend upward with a noticeable increase to 1 in 36 children less than 8 years of age in the recent MMWR. There are many factors linked to the substantially increased burden of seeking mental health services, and clinically these individuals are likely to present for impairments associated with co-occurring conditions. The advances in cutting-edge research and the understanding of co-occurring conditions in addition to psychosocial interventions have provided a window of opportunity for psychopharmacological interventions given the limited availability of therapeutics for core symptomatology. The off-label psychopharmacological treatments for these co-occurring conditions are central to clinical practice. However, the scattered evidence remains an impediment for practitioners to systematically utilize these options. The review collates the crucial scientific literature to provide stepwise treatment alternatives for individuals with ASD; with an aim to lead practitioners in making informed and shared decisions. There are many questions about the safety and tolerability of off-label medications; however, it is considered the best practice to utilize the available empirical data in providing psychoeducation for patients, families, and caregivers. The review also covers experimental medications and theoretical underpinnings to enhance further experimental studies. In summary, amidst the growing clinical needs for individuals with ASD and the lack of approved clinical treatments, the review addresses these gaps with a practical guide to appraise the risk and benefits of off-label medications.

Subsume Pediatric Headaches in Psychiatric Disorders? Critiques on Delphic Nosology, Diagnostic Conundrums, and Variability in the Interventions.

PURPOSE OF REVIEW: Tension-type headache (TTH) continues to be the most prevalent type of headache across all age groups worldwide, and the global burden of migraine and TTH together account for 7% of all-cause years lived with disability (YLDs). TTH has been shown to have a prevalence of up to 80% in several studies and presents a wide range and high variability in clinical settings. The aim of this review is to identify gaps in diagnostics, nosology, and variability in the treatment of children and adolescents who present with headaches without an identifiable etiology. RECENT FINDINGS: Migraine and TTH have been debated to have more similarities than distinctions, increasing chances of misdiagnosis and leading to significant cases diagnosed as probable TTH or probable migraine. The lack of specificity and sensitivity for TTH classification often leads to the diagnosis being made by negating associated migraine symptoms. Although pathology is not well understood, some studies have suggested a neurological basis for TTH, in need of further validation. Some research indicates that nitric oxide signaling plays an integral part in the pain mechanisms related to TTH. Analgesics and non-steroidal anti-inflammatories are usually the first lines of treatment for children with recurring headaches, and additional treatment options include medication and behavioral therapies. With high prevalence and socioeconomic burden among children and adolescents, it's essential to further study Tension-type headaches and secondary headaches without known cause and potential interventions. Treatment studies involving randomized controlled trials are also needed to test the efficacy of various treatments further.

Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population.

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.

Profiling of the ß-glucosidases identified in the genome of Penicillium funiculosum: insights from genomics, transcriptomics, proteomics, and homology-modeling studies.

The enzymatic conversion of lignocellulosic biomass to bioethanol depends on efficient enzyme systems with ß-glucosidase as one of the key components. In this study, we performed in-depth profiling of the various ß-glucosidases present in the genome of the hypercellulolytic fungus Penicillium funiculosum using genomics, transcriptomics, proteomics, and molecular dynamics simulation approaches. Of the eight ß-glucosidase genes identified in the P. funiculosum genome, three were predicted to be extracellular based on signal peptide prediction and abundance in the secretome. Among the three secreted ß-glucosidases, two belonged to the GH3 family and one belonged to the GH1 family. Homology models of these proteins predicted a deep and narrow active site for the GH3 ß-glucosidases (PfBgl3A and PfBgl3B) and a shallow open active site for the GH1 ß-glucosidase (PfBgl1A). The enzymatic assays indicated that P. funiculosum-secreted proteins showed high ß-glucosidase activities with prominent bands on the 4-methylumbelliferyl ß-D-glucopyranoside zymogram. To understand the contributory effects of each of the three secreted ß-glucosidases (PfBgls), the corresponding gene was deleted separately, and the effect of the deletion on the ß-glucosidase activity of the secretome was examined. Although not the most abundant, PfBgl3A was found to be one of the most important ß-glucosidases, as evidenced by a 42% reduction in ß-glucosidase activity in the ΔPfBgl3A strain. Our results advance the understanding of the genetic and biochemical nature of all ß-glucosidases produced by P. funiculosum and pave the way to design a superior biocatalyst for the hydrolysis of lignocellulosic biomass. IMPORTANCE Commercially available cellulases are primarily produced from Trichoderma reesei. However, external supplementation of the cellulase cocktail from this host with exogenous ß-glucosidase is often required to achieve the desired optimal saccharification of cellulosic feedstocks. This challenge has led to the exploration of other cellulase-producing strains. The nonmodel hypercellulolytic fungus Penicillium funiculosum has been studied in recent times and identified as a promising source of industrial cellulases mainly due to its ability to produce a balanced concoction of cellulolytic enzymes, including ß-glucosidases. Various genetic interventions targeted at strain improvement for cellulase production have been performed; however, the ß-glucosidases of this strain have remained largely understudied. This study, therefore, reports profiling of all eight ß-glucosidases of P. funiculosum via molecular and computational approaches. The results of this study provide useful insights that will establish the background for future engineering strategies to transform this fungus into an industrial workhorse.

Focus on rural adolescent cannabis use and abuse: ignored epidemiologic trends, unique risks, long-term concerns, and hope.

Cannabis-related issues for adolescents and young adults are emerging from the shadow of rural opioid addiction and deaths. The rural pediatric population has multiple risk factors putting them at increased risk for adverse consequences with the expansion of cannabis legalization across the United States. Research in this area is rich but scattered across professional disciplines. Differences in demographics and cultures between rural and urban youth are gaining attention. Epidemiological factors relevant to rurality as a risk for cannabis and other substance use are considered for formulating clinical care, public policymakers, and future research. Race, culture, community stability, basic demographics of age, gender, educational status, and demands for more and better, accessible services for rural, nonmetropolitan areas comprise factors for consideration and are detailed. Research findings provide direction for policymakers and clinicians for prevention and intervention efforts to improve care for rural populations, validating and expanding upon insights gained to date.

A panorama of the medicolegal aspects of suicide assessments: integrating multiple vantage points in improving quality, safety, and risk management.

Epidemiological trends in global suicides have been of serious concern in the last decade. The burden of higher expectations in the assessment of suicidal behaviors on mental health professionals is mounting. However, the suicidal risk assessment has many evolving and moving parts, and is one of the most heavily researched fields in psychiatry. Although it is clear from current empirical research that suicide cannot accurately be predicted, the standard of care from regulatory bodies and professional organizations dictates the use of established measures and following consensus guidelines. However, the legal system has different parameters to assess for the deviation from these standards and views it from a different vantage point. Therefore, it is imperative to know these critical multifaceted panoramas of suicide assessment. Considering the gaps within suicide risk assessment tools, we propose that appropriate documentation and thorough treatment planning are key to navigating the complex medicolegal risks. These approaches are useful for risk management and improve clinical outcomes, quality of care, and overall patient safety.

Duration of untreated autism in rural America: emerging public health crisis.

The rural areas have been at the receiving end amidst mental health disparity across the USA. There is a serious and concerning divide among ones with autism spectrum disorders (ASDs) living in underserved areas as compared to urban residents. With the higher than ever prevalence of ASD as per the recent reports of the Centers for Disease Control and Prevention; there is a need for a closer look at the prevailing issues. The trends are reflecting marked underdiagnosis, late diagnosis, lack of evidence-based diagnostic measures and interventions. These factors interplay in worsening the mental health crisis and there is an urgent need for corrective measures to address these highly modifiable problems.

Do antibullying laws in the United States have an impact?

Bullying is an omnipresent problem with high prevalence in children and adolescents. There are many antibullying state laws and practices in place however its real level impact is ambiguous at best. We studied the prevalence of bullying in the United States, examine the practices, laws, and interventions in place to prevent bullying and its real-life impact. Various studies have reported that the ground-level change brought about by these policies and programs varies and is not quite significant. The effectiveness of existing policies and legislations remains unclear and measurable objective change or impact is not yet observed. Therefore, a rethink of the strategies is needed. The focus must be on community-level programs and interventions with inclusive approaches involving all the stakeholders are critical for addressing this menace.

Nebulized dexmedetomidine for attenuating hemodynamic response to laryngoscopy and endotracheal intubation in adult patients undergoing surgeries under general anaesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sympathetic stimulation associated with laryngoscopy and endotracheal intubation (ETI) may lead to adverse cardio-/cerebro-vascular events in susceptible patients. Nebulization is a novel route for dexmedetomidine administration providing a large surface area for absorption while avoiding bradycardia and hypotension associated with intravenous route. We aimed to evaluate the efficacy and safety of dexmedetomidine nebulization for attenuating hemodynamic response to ETI in adult patients undergoing surgery under general anaesthesia. METHODS: This systematic review was registered prospectively in the International Prospective Register of Systematic Reviews (CRD42023403624). PubMed, Embase (OvidSP), Cochrane library, Scopus (Elsevier), Web of Science (Clarivate) and Google Scholar were systematically searched from database inception until March 31, 2023. Two reviewers independently screened titles, abstracts and then full text against pre-specified eligibility criteria. Randomized controlled trials (RCTs) assessing effect of dexmedetomidine nebulization on hemodynamic response to ETI in adult patients undergoing surgeries under general anaesthesia were included. All studies reporting heart rate and systolic blood pressure at baseline and various time points after ETI were included. A pre-piloted data extraction form, Cochrane revised risk-of-bias tool (ROB 2) tool, GRADE approach and RevMan 5.4.1 (Cochrane Collaboration, Copenhagen, Denmark) were used for data extraction, risk of bias assessment, rating certainty of evidence and data synthesis respectively. Mean difference and relative risk with 95% Confidence Interval (CI) were used for continuous and dichotomous variables respectively. RESULTS: Six RCTs randomized 480 patients with ASA I/II patients aged < 60 years of age and undergoing elective surgeries to receive either dexmedetomidine (n = 240) or saline nebulization (n = 240). Except for one RCT which used 2 µg/kg, all other RCTs used dexmedetomidine dose of 1 µg /kg. Heart rate, systolic, diastolic and mean blood pressure were significantly lower in the dexmedetomidine group at all the measured time points after laryngoscopy and ETI with the only exception being systolic blood pressure at 3 min [mean difference -13.86 (95% CI -30.01 to 2.99), p = 0.09]. Bradycardia and hypotension as adverse effects were absent across the included studies. However, only one-third of the included studies had a low risk of bias and strength of evidence was very low according to the GRADE assessment. CONCLUSIONS: Compared to placebo, premedication with dexmedetomidine nebulization was associated with lower HR and BP following ETI without any risk of bradycardia and hypotension. However, the strength of evidence was very poor and came from just one country. Future well designed and conducted studies in different populations are warranted. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023403624.

Comprehensive coordinated community based palliative care (C3PaC) model for cancer patients in North India: a mixed-method implementation research study protocol.

BACKGROUND: Cancer remains an escalating and challenging public health issue. The management, especially palliative care (PC), is disintegrated and out of reach of in need patients. The overall aim of the project is to develop a feasible and scalable Comprehensive Coordinated Community based PC model for Cancer Patients (C3PaC); congruent with socio-cultural, context and unmet needs in north India. METHODS: A mixed method approach will be used for three-phased pre- and post-intervention study in one of the districts of North India, having a high incidence of cancer. During phase I, validated tools will be used for quantitative assessment of palliative needs among cancer patients and their caregivers. Barriers and challenges for provision of palliative care will be explored using in-depth interviews and focus group discussions among participants and health care workers. The findings of phase I along with inputs from national experts and literature review will provide inputs for the development of the C3PAC model in phase II. During phase III C3PAC model will be deployed over a period of 12 months and its impact assessed. Categorical and continuous variables will be depicted as frequency (percentages) and mean ± SD/median (IQR) respectively. Chi-square test/Fischer test, independent samples Student t-tests and Mann-Whitney U tests will be used for categorical, normally and non-normally distributed continuous variables, respectively. Qualitative data will be analyzed using thematic analysis using Atlas.ti 8 software. DISCUSSION: The proposed model is designed to address the unmet palliative care needs, to empower community-based healthcare providers in comprehensive home-based PC and to improve the quality of life of cancer patients and caregivers. This model will provide pragmatic scalable solutions in comparable health systems particularly in low- and lower-middle Income countries. TRIAL REGISTRATION: The study has been registered with the Clinical Trial Registry-India (CTRI/2023/04/051357).

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial.

OBJECTIVE: This study aimed to assess the safety and effectiveness of a new charge-distributed multiphase stimulation paradigm during an extended spinal cord stimulation (SCS) trial. MATERIALS AND METHODS: This prospective, multicenter, randomized, single-blind, feasibility study included participants with chronic low back and/or leg pain and baseline numerical rating scale (NRS) for overall pain intensity ≥6. After a successful commercial SCS trial, participants were randomized to multiphase SCS therapy A (approximately 600-1500 Hz) or B (approximately 300-600 Hz), delivered via an investigational external pulse generator and existing leads during an 11-to-12-day testing period. Primary end points were mean NRS change from baseline to final in-office visit for each multiphase therapy and between therapies. Secondary end points included mean NRS change from end of commercial trial to final study visit and incidence of device-related adverse events (AEs). Additional measures included patient-reported outcomes collected at home through electronic watches and written diaries. Power usage was compared between multiphase and commercial therapies. RESULTS: A total of 122 participants initiated a commercial trial; 77 were randomized to a multiphase arm, and 65 completed the study. Reductions in mean NRS scores from baseline to final study visit were significant for multiphase therapy A and B (-4.3 and -4.7, respectively; both p < 0.0001). There was no statistically significant difference in mean NRS reduction or percent pain relief between multiphase therapies. In an additional analysis, 63.9% of participants reported greater pain relief with multiphase than with commercial SCS therapy in the at-home setting. On average, multiphase required less power than did commercial devices. One non-serious device-related AE was reported, and no infections occurred during the extended trial. CONCLUSIONS: Multiphase SCS effectively reduced pain in participants with chronic low back and/or leg pain during a trial, with no unanticipated device-related AEs reported. Future studies should evaluate long-term effectiveness of multiphase stimulation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03594266.

Microbial methylglyoxal metabolism contributes towards growth promotion and stress tolerance in plants.

Plant growth promotion by microbes is a cumulative phenomenon involving multiple traits, many of which are not explored yet. Hence, to unravel microbial mechanisms underlying growth promotion, we have analysed the genomes of two potential growth-promoting microbes, viz., Pseudomonas sp. CK-NBRI-02 (P2) and Bacillus marisflavi CK-NBRI-03 (P3) for the presence of plant-beneficial traits. Besides known traits, we found that microbes differ in their ability to metabolize methylglyoxal (MG), a ubiquitous cytotoxin regarded as general consequence of stress in plants. P2 exhibited greater tolerance to MG and possessed better ability to sustain plant growth under dicarbonyl stress. However, under salinity, only P3 showed a dose-dependent induction in MG detoxification activity in accordance with concomitant increase in MG levels, contributing to enhanced salt tolerance. Furthermore, salt-stressed transcriptomes of both the strains showed differences with respect to MG, ion and osmolyte homeostasis, with P3 being more responsive to stress. Importantly, application of either strain altered MG levels and subsequently MG detoxification machinery in Arabidopsis, probably to strengthen plant defence response and growth. We therefore, suggest a crucial role of microbial MG resistance in plant growth promotion and that it should be considered as a beneficial trait while screening microbes for stress mitigation in plants.

Disruptive mood dysregulation disorder: does variance in treatment responses also add to the conundrum? The widening gap in the evidence is a signal needing attention.

The new diagnosis of disruptive mood dysregulation disorder (DMDD) was introduced in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, to address the overdiagnosis of bipolar disorder in children and adolescents. However, there are ongoing debates about its nosology given chronic persistent irritability in children and adolescents has contextual valence. Those meeting the criteria for DMDD may, in fact, have an oppositional defiant disorder, attention deficit hyperactivity disorder, or other behavioral disorders. Similarly, in the last few years, there are many different types of treatment studies that have also yielded mixed results. These counterintuitive findings need a meticulous review for a wider debate given its clinical utility for patients, families, and practicing clinicians.

Pulse Dosing of 10-kHz Paresthesia-Independent Spinal Cord Stimulation Provides the Same Efficacy with Substantial Reduction of Device Recharge Time.

OBJECTIVE: This study was designed to assess whether using pulse dosing (PD) (regularly cycled intermittent stimulation) of high-frequency 10-kHz spinal cord stimulation (10-kHz SCS) can reduce device recharge time while maintaining efficacy in patients with chronic intractable back pain with or without leg pain. DESIGN: Prospective, multicenter, observational study. METHODS: Patients successfully using 10-kHz SCS at 100%ON (i.e., continuously with no PD) for >3 months were consecutively enrolled. After a 1-week baseline period of documenting their pain twice daily on a 0-10 numerical rating scale (NRS) using 100%ON of their "favorite" program, all subjects were reprogrammed to 14%PD for 10-14 days. If subjects preferred 14%PD to 100%ON, they were programmed to 3%PD; otherwise, they were programmed to 50%PD. Subjects used this next program for another 10-14 days. Subjects then entered a 3-month observational period during which they were requested to use but not limited to their most preferred %PD program. Toward the end of 3 months, subjects completed a 7-day NRS diary and indicated a final %PD program preference. Study endpoints included %PD preference, mean diary NRS by %PD, and daily minutes and patterns of charging. RESULTS: Of 31 subjects completing the study, 81% preferred less than 100%ON. Among the subjects, 39% preferred 3%PD, 32% preferred 14%PD, 10% preferred 50%PD, and 19% preferred 100%ON. Average daily charge durations were 8.3 ± 3.1 minutes for 3%PD, 13.9 ± 4.9 minutes for 14%PD, 26.2 ± 7.4 minutes for 50%PD, and 43.8 ± 10.9 minutes for 100%ON. Regression modeling suggested that pain relief was weighted as more than twice as influential as charging in preference for reduced %PD. CONCLUSIONS: This prospective study suggests that 10-kHz SCS therapy with PD may be successfully used in a large majority of 10-kHz SCS responders, maintaining efficacy while reducing device charging time by nearly two thirds.

Cervical Spinal Cord Stimulation for Trigeminal Neuralgia: a Narrative Review.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic neuropathic pain condition affecting one or more divisions of the fifth cranial (trigeminal) nerve. TN is defined by recurrent unilateral electric shock-like pain that is abrupt in both onset and termination. The pain is triggered by innocuous sensory stimuli and is classified as either classic TN, related to vascular compression; secondary TN, due to a tumor along the trigeminal nerve or an underlying disease like multiple sclerosis; or idiopathic TN. Among the various therapies available for TN, carbamazepine remains the first-line treatment. Newer medications have demonstrated efficacy in patients who do not respond to or cannot tolerate carbamazepine. When medical management and neuroablative procedures fail, spinal cord stimulation (SCS) serves as a promising and popular option, with an estimated 34,000 SCS procedures performed annually worldwide. SCS employs the implantation of electrical leads in the epidural space to manage pain. PURPOSE OF REVIEW: A review of literature was conducted to explore the use of cervical spinal cord stimulation (SCS) for the treatment of trigeminal neuralgia. METHODS: A MEDLINE/PubMed search using the search terms "spinal cord stimulation" and "trigeminal neuralgia" was employed to find any case reports and research studies (retrospective studies, double-blinded studies, observational studies) on the topic. No date limiters were used for the search. The initial search resulted in 76 non-duplicate entries from the database. After application of the search criteria, 58 studies were excluded because they were not relevant to the study. A further detailed review of the included articles was conducted by all the reviewers. During this phase of the review, additional 6 studies were excluded. A total of 11 studies were included: 7 case reports and 4 retrospective review studies. RECENT FINDINGS: In the review, we discuss 7 different case reports on the use of cervical SCS for trigeminal neuralgia and an additional 4 retrospective studies reviewing outcomes and pain relief in patients who underwent treatment. The case reports and retrospective studies reviewed demonstrated that TN patients realized > 50% pain relief following permanent electrode implantation. In all the cases discussed, complications from SCS were rare and/or not reported. Additionally, most of the cases report that patients who had adequate pain relief from SCS were able to wean off, or significantly reduce, oral medications given the vast improvement in pain reduction. CONCLUSIONS: Cervical spinal cord stimulation (SCS) is a safe and effective procedure for patients with trigeminal neuralgia (TN) who have refractory pain despite the use of medications. In many cases, the procedure provides an adequate level of pain relief with very few complications or side effects. The vast majority of current research on the use of cervical SCS for TN currently consists of case reports and retrospective analysis. In order to further evaluate the efficacy of SCS for treatment, large-scale randomized controlled studies or observational studies need to be conducted to properly evaluate SCS as a treatment modality for trigeminal neuralgia.

IgG4-Related Disease: A Clinical Case Series From a Tertiary Care Center in India.

AIM: Immunoglobulin G4-related disease (IgG4-RD) is often an unrecognized, rare fibroinflammatory condition that can involve various organ systems. This study aimed to identify the different clinical patterns of this disease in a single center in North India. METHODS: Patients were diagnosed on the basis of published diagnostic criteria for IgG4-RD. Patients' presenting complaints; epidemiologic profiles; and laboratory, radiologic, and histologic findings along with the treatment and outcomes were collected and analyzed. RESULTS: In total, 70 patients were diagnosed with the disease. The female-to-male ratio was 0.94:1, and it increased with multiorgan involvement. The mean age of patients was 41.4 years, and the majority of the patients (65.7%) were younger than 50 years. Patients were diagnosed as possible (38.57%), probable (32.85%), and definite (28.57%) IgG4-RD. The incidence of the involvement of orbital and periorbital tissues was the highest (52.9%); however, 13% of the patients had multiple organ involvement. Patients with involvement of the retroperitoneal tissues and the lymph nodes were 8.5% and 5.7%, respectively. Increased serum IgG4 levels were found in 74.3% of the patients with single-organ involvement, whereas all patients with multiorgan involvement had increased IgG4 levels. The majority of patients (94.3%) required immunosuppressive medications along with corticosteroids. Azathioprine was the most commonly used (72.8%) immunosuppressive medication. Rituximab was used in 17.1% of the patients, of whom only one had multisystem involvement. CONCLUSIONS: This study depicts the most common patterns of organ involvement, along with the epidemiologic, laboratory, histologic, and radiologic data and response to treatment, in IgG4-RD, with a definite ophthalmology referral bias.

COVID-19 Palliative and End-of-Life Care Plan: Development and Audit of Outcomes.

Objectives: Palliative care (PC) referral in serious and critical COVID-19 improves decision-making, health resource utilisation, end-of-life symptom management and family support. In this study, we explored developing a systematic decision-making matrix for PC referral in COVID-19 and audited its outcomes. Materials and Methods: A team of interdisciplinary experts developed a hospital COVID-19 PC plan. PC referral and outcomes of PC referral in hospitalised COVID-19 patients were audited. Results: Out of 1575 inpatients, 1066 (67.7%) had mild and 509 (32.3%) had serious and critical COVID-19 illness. Among 50 (3.1%) referred to PC, 5 (0.4%) had mild and 45 (8.8%) had serious and critical COVID-19 illness. Out of 45 serious and critical COVID-19 patients referred to PC, 38 (84%) received end-of-life care (EOLC), 4 (9%) self-discharged against medical advice and 3 (7%) recovered. Forty-seven (94%) were referred for goals-of-care discussion. About 78% received opioids, 70% benzodiazepines and 42% haloperidol for symptom management. Among 45 serious and critical COVID-19 patients referred to PC, foregoing life-sustaining treatment was documented in 43 (96%) but implemented only in 23 (53%). Out of 38 who received EOLC, ICU was the place of death in 31 (82%) and ward in 7 (18%). Conclusion: Despite interdisciplinary experts developing a hospital COVID-19 PC, low referral of serious and critical COVID-19 patients to PC was observed. PC referral enabled access to management of end-of-life symptoms and facilitated limitation of life-sustaining treatment in some COVID-19 patients with serious illness. Educating critical care physicians about the scope of PC in the COVID-19 setting might improve PC referral.

The Concept of Respite in Palliative Care: Definitions and Discussions.

PURPOSE OF THE REVIEW: The definition of respite care remains unclear and its purpose and effectiveness are unproven till date. This paper reviews the current evidence regarding definition and efficacy of respite care, as well as the different programs, models, and interventions employed to deliver the same. RECENT FINDINGS: A scoping search identified the relevant literature to be included in the review. The current evidence reiterates the lack of clarity in defining and delineating the purpose of respite care. Recent empirical evidence supports the effectiveness of respite care with clear benefits for the carers, patients, their families, and the healthcare system. Along with inpatient, home, and hospice care, respite care is considered as an essential component of palliative care. Evidence, although weak, supports the efficacy of respite care. High-quality studies with clear outlining of the scope of the services and resolution of ambiguities pertaining to its definition are warranted to fill the gaps in knowledge.

Three confounded high-risk groups for suicide in adolescents and young adults.

Suicide rates among adolescents and young adults have been increasing in the last decade. The current knowledge of the warning signs, risk factors, and the use of screening tools has many gaps. There are many views from within, critics, survivors, and advocacy groups to focus more on the contextual understanding of symptomatology. In clinical practice, many of these high-risk groups fail to raise the red flags due to the complex and ambiguous nature of presentations. Therefore, these groups need greater attention, and given their counter-initiative nature, they challenge the current approaches to address suicidality in adolescents and young adults.