Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines.

Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.

Narrative storytelling as mental health support for women experiencing gender-based violence in Afghanistan.

RATIONALE: Experiencing gender-based violence (GBV) can have serious consequences for women's mental health. However, little is known about how to address the health consequences of GBV against women in high-prevalence settings where GBV is widely accepted as normal. OBJECTIVE: This study examines the potential for narrative storytelling to support women's mental health and alleviate the suffering caused by GBV in high-prevalence settings. It adopts a symbolic interactionist perspective to explore the perceptions and lived experiences of women living in safe houses for GBV in Afghanistan. METHOD: In-depth semi-structured interviews were carried out with women (n = 20) in two Afghanistan safe houses between March and May 2017. The data were analysed both inductively and deductively using thematic network analysis. RESULTS: The findings reveal the stigmatising and traumatic experiences many women have had when telling their stories of GBV in this context. In contrast, storytelling under supportive conditions was perceived to be a highly valuable experience that could help formulate positive social identities and challenge broader social structures. The supportive conditions that contributed to a positive storytelling experience included the presence of a sympathetic non-judgemental listener and a supportive social environment. CONCLUSIONS: These findings offer an alternative to biomedical models of mental health support for women experiencing GBV in high-prevalence settings. They raise the importance of tackling broader social changes that challenge patriarchal social structures, and highlight the potential role that narrative storytelling approaches can play in high-prevalence settings like Afghanistan.

Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin.

Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to pain-related maladaptive plasticity in the frontal cortex. We sought to model cognitive deficits in mice with neuropathic pain to examine maladaptive morphological plasticity in the mPFC and to assess the effects of several therapeutics. We used an attentional set-shifting task in mice with spared nerve injury (SNI) who received either a single intrathecal injection of an analgesic dose of clonidine, 7 d of 100 mg/kg gabapentin, or 7 d of 200 mg/kg metformin. Male SNI mice were significantly more impaired in the set-shifting task than females. This deficit correlated with a loss of parvalbumin (PV) and reductions in axon initial segment (AIS) length in layers 5/6 of the infralimbic (IL) cortex. Acute pain relief with clonidine had no effect on set-shifting performance, whereas pain relief via 7 day treatment with gabapentin worsened the impairment in both SNI and sham mice. Gabapentin reversed the PV loss in the IL but had no effect on AIS length. Treatment with the AMPK-activator metformin completely reversed the pain-related cognitive impairment and restored AIS length in the IL but had little effect on PV expression. Our findings reveal that neuropathic pain-related cognitive impairments in male mice are correlated to bilateral morphological changes in PV interneurons and layer 5/6 IL pyramidal neuron AIS. Pain relief with metformin can reverse some of the functional and anatomical changes.SIGNIFICANCE STATEMENT Cognitive impairments are a comorbidity of neuropathic pain but are inadequately addressed by existing therapeutics. We used a neuropathic pain model in mice to demonstrate that male (but not female) mice show a robust pain-related deficit in attentional set-shifting, which is associated with structural plasticity in axon initial segments in the infralimbic cortex. These deficits were completely reversed by 7 day treatment with the antidiabetic drug metformin, suggesting that this drug can be repurposed for the treatment of neuropathic pain and its cognitive comorbidities. Our findings have implications for our understanding of how neuropathic pain causes structural plasticity in the brain, and they point to a marked sexual dimorphism in neuropathic pain mechanisms in mice.

Comparison of Topical Versus Peribulbar Anesthesia for 23G Pars Plana Vitrectomy.

OBJECTIVE: To compare the safety and efficacy of topical anesthesia versus peribulbar anesthesia for 23-gauge pars plana vitrectomy. STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Ophthalmology Department, Lahore General Hospital, Ameer-ud-Din Medical College, Postgraduate Medical Institute, Lahore from April 2013 to March 2016. METHODOLOGY: A total of 110 patients were equally divided (n=55) in group A (topical anesthesia) and group B (peribulbar anesthesia). In group A, pledget soaked with 0.5% proparacaine hydrochloride were placed in the superior and inferior fornices three minutes before surgery, and removed just before surgery. For group B patients, 3 ml of 0.5% bupivacaine was used for peribulbar anesthesia three minutes before surgery. Surgical time was noted from the placement of pledget in fornix till the eye pad placed in group A, and from the time of peribulbar anesthesia in group B till the eye pad placed at the end of surgery. All data was recorded in Excel sheet and p-values were calculated using online OpenEpi. RESULTS: The mean age of the patient was 56.28 ±13.76 years. Male patients were 78 (70.9%) and female patients were 32 (29.1%). Mean duration of surgery was 30.32 ±7.07 minutes and mean pain score was 2.30 ±0.98. There was a significant difference with respect to mean duration of surgery in patients who were given topical anesthesia (32.52 ±6.92 minutes) versus those given peribulbar anesthesia (28.12 ±6.57 minutes, p<0.001). Mean pain score in topical anesthesia group (3.11 ±0.89) was significantly higher as compared to peribulbar anesthesia group (2.67 ±0.91, p=0.011). CONCLUSION: Topical anesthesia is as effective as peribulbar anesthesia in terms of patient comfort and duration of surgery for 23-G pars plana vitrectomy in patients with vitreous hemorrhage.

Computerized stereotactic brain biopsies: an experience of 15 patients at Ayub Teaching Hospital.

BACKGROUND: Deep seated lesions of the brain cannot be approached by conventional neurosurgical approach stereotactic system offers minimally invasive and accurate approach to such lesions. This study was carried out with an objective to determine the safety, efficacy and diagnostic yield of stereotactic biopsies of brain lesions using Brown-Roberts-Wells (BRW) system. METHODS: This study was carried out in patients with intracranial lesions at Ayub teaching hospital Abbottabad from September 1999 to October 2003. Suitable patients with intra cranial lesions underwent computerized stereo tactic biopsy with BRW system. Tissue specimens were analyzed in histopathology department of the Ayub Medical College and results were obtained. Data was analyzed via computer software SPSS 8.0 version for windows. RESULTS: Fifteen patients were selected for stereotactic brain biopsy. Age ranged from 15 years to 54 years. Among them 09 (60%) were male and 06 (40%) were female patients. Out come of the procedure was highly promising in terms of safety and positive diagnostic yield in 14 patients (93.3%), and histopathalogical validity of results (93.3%). Only one patient suffered mild neurological deficit (6.7%), one patient had inconclusive tissue diagnosis and invalid result (6.7%). biopsy proven lesion was astrocytoma in 04 patients (26.7%), anaplastic astrocytoma in 04 (26.7%), gliomatosis in 02 (13.3%), tuberculomas in 03 (20.0%). metastatic adenocarcinomas in 01 (6.7%) and lymphoma in 01(6.7%). CONCLUSIONS: We conclude that computerized stereotactic brain biopsy is safe and effective procedure with a high diagnostic yield at our center.