Two-Year Duration of Immunity of Inactivated Poliovirus Vaccine: A Follow-up Study in Pakistan in 2020.

This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies 2 years postimmunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% 1 year and 2 years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trials Registration . NCT03286803.

One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh.

BACKGROUND: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. METHODS: We conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9-13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. RESULTS: A single fIPV dose at age 9-13 months yielded 75% (95% confidence interval [CI], 6%-82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%-97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion. CONCLUSIONS: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic. CLINICAL TRIAL REGISTRATION: NCT03890497.

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique.

BACKGROUND: The monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2. METHODS: We conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9-22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p). RESULTS: We enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%-62.1%) and 60.6% (52.2%-68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, -5.0% to 19.0%). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.

Randomized Controlled Clinical Trial of Bivalent Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine in Nigerian Children.

BACKGROUND: We conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016-March 2017, well past the trivalent OPV-bOPV switch in April 2016. METHODS: This was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age. RESULTS: Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7-99.8) and 98.1% (95% CI, 88.2-94.8) in Arm A and 89.6% (95% CI, 85.4-93.0) and 98.5% (95% CI, 96.3-99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2-77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8-97.9). CONCLUSIONS: This first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.

Immunogenicity of Intramuscular Fractional Dose of Inactivated Poliovirus Vaccine.

BACKGROUNDS: Intradermal (id) fractional inactivated poliovirus vaccine ([fIPV] one fifth of normal IPV dose) is safe and immunogenic; however, id administration is perceived as difficult. We compared fIPV immunogenicity administered id or intramuscularly (im). METHODS: This noninferiority trial was conducted among polio vaccine-naive Cuban infants who received 2 IPV doses at 4 and 8 months of age. Infants were randomized into 4 arms: (A) fIPV, 0.1 mL im; (B) fIPV, 0.2 mL im; (C) fIPV, 0.1mL id; and (D) IPV, 0.5 mL im. Blood collected before and after vaccinations was tested for poliovirus-neutralizing antibodies. RESULTS: A total of 196 of 214 (91.6%) enrolled children completed study. Seroconversion after 2 IPV doses in each arm were as follows: (A) 97.3% (90.6-99.7), 98.7% (92.7-99.9), and 90.5% (81.5-96.1) for serotypes 1, 2, and 3, respectively; (B) 97.2% (90.3-99.7), 100%, 95.8% (88.3-99.1) for serotypes 1, 2, and 3, respectively; (C) 89.3% (71.8-97.7), 92.9% (76.5-99.1), 82.1% (63.1-93.9) for serotypes 1, 2, and 3, respectively; and (D) 100%, 100%, 100% for serotypes 1, 2, and 3, respectively. Seroconversion with fIPV im was noninferior to fIPV id for all serotypes. CONCLUSIONS: We demonstrated noninferiority of fIPV im compared with id when administered at 4 and 8 months of age. Further investigations in an earlier infant schedule should be pursued to explore fIPV im as option for dose-sparing strategy in countries reluctant to use fIPV id due to programmatic difficulties of id administration.

Structured, functional histology practical modules: An answer to medical students' histology nightmare and the way forward for relevant histology instruction in the Indian undergraduate medical curriculum?

Background: . It is often a challenge to make histology instruction relevant and interesting. We assessed whether structured, worksheet-based histology practical modules with emphasis on functional histology and clinical application, would improve the learning experience and help students focus on relevant functional and clinical correlates. Methods: . In eight practical sessions, 100 students worked as two groups, one group undergoing new intervention practical modules and another group undergoing the routine laboratory practical exercises as a control group. For every pair of laboratory practical exercises, the groups alternated. Spot tests administered in the following week assessed identification ability as well as application of knowledge. Feedback was collected in the form of written questionnaires from faculty and students, student focus group discussion and in-depth interviews. Analysis of test scores as well as feedback was done. Results: . Test scores were better following the intervention method when comparing the overall score as well as its subcomponents of identification and analysis-type questions (p<0.001). The weaker performers in the class as well as high achievers showed better test scores with the intervention method (p<0.001). Feedback from faculty and students reflected better student experience with the intervention method. Suggestions were made to improve the approach further. Conclusion: . Studying histology through structured modules, which emphasize functional and clinical correlates, appears to improve the identification and application ability of the student as well as the student experience.

Poliovirus Type 2 Seroprevalence Following Full- or Fractional-Dose Inactivated Poliovirus Vaccine in the Period After Sabin Type 2 Withdrawal in Sri Lanka.

BACKGROUND: In July 2016, Sri Lanka replaced 1 intramuscular dose of inactivated poliovirus vaccine (IPV) with 2 doses of intradermal fractional-dose IPV (fIPV) in its routine immunization schedule. We carried out a survey of seroprevalence of antipolio antibodies in children who received 2 fIPV doses and compared it with those who received 1 full IPV dose. METHODS: Children born between March and December 2016 were randomly selected from 3 Sri Lankan districts (Colombo, Badulla, and Anuradhapura). Serum samples were collected and tested for presence of neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS: Seroprevalence of antipolio antibodies was 100% in all districts for poliovirus type 1 and poliovirus type 3; it ranged between 90% and 93% for poliovirus type 2 (PV2) in children who received 1 full IPV dose and between 78% and 100% in those receiving 2 fIPV doses (P = .22). The median reciprocal titers of anti-PV2 antibodies were similar in children who received full-dose IPV and those who received fIPV (1:64 vs 1:45, respectively; P = .11). CONCLUSIONS: Our study demonstrated not only that Sri Lanka succeeded in maintaining very high primary immunization coverage also but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application. The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV.

Rapid Disappearance of Poliovirus Type 2 (PV2) Immunity in Young Children Following Withdrawal of Oral PV2-Containing Vaccine in Vietnam.

BACKGROUND: Due to global shortage of inactivated poliovirus vaccine and withdrawal of oral vaccine containing poliovirus type 2 (PV2), a PV2-containing vaccine was not used in Vietnam May 2016 to October 2018. We assessed the population immunity gap to PV2. METHODS: A cross-sectional survey in children aged 1-18 months was carried out in January 2018. One blood sample per child was analyzed for presence of poliovirus neutralizing antibodies. In children with detectable anti-PV2 antibodies, a second sample was analyzed 4 months later to distinguish between passive (maternally derived) and active (induced by secondary transmission or vaccination) immunity. RESULTS: Sera were obtained from 1106/1110 children. Seroprevalence of PV2 antibodies was 87/368 (23.6%) at age 1-7 months, 27/471 (5.7%) at 8-15 months, and 19/267 (7.1%) at 16-18 months. Seroprevalence declined with age in the 1-7 months group; in the 8-18 months group there was no significant change with age. Four months later, 11/87 (14%), 9/27 (32%), and 12/19 (37%) remained seropositive in 1-7, 8-15, and 16-18 months age groups, respectively. CONCLUSIONS: We found declining immunity to PV2, suggesting Vietnam is at risk for an outbreak of type 2 vaccine-derived poliovirus following virus importation or new emergence.

End-of-life decisions: A retrospective study in a tertiary care teaching hospital in India.

Background & objectives: In developing countries like India, there is a lack of clarity regarding the factors that influence decisions pertaining to life supports at the end-of-life (EOL). The objectives of this study were to assess the factors associated with EOL-care decisions in the Indian context and to raise awareness in this area of healthcare. Methods: This retrospectively study included all patients admitted to the medical unit of a tertiary care hospital in southern India, over one year and died. The baseline demographics, economic, physiological, sociological, prognostic and medical treatment-related factors were retrieved from the patient's medical records and analysed. Results: Of the 122 decedents included in the study whose characteristics were analyzed, 41 (33.6%) received full life support and 81 (66.4%) had withdrawal or withholding of some life support measure. Amongst those who had withdrawal or withholding of life support, 62 (76.5%) had some support withheld and in 19 (23.5%), it was withdrawn. The documentation of the disease process, prognosis and the mention of imminent death in the medical records was the single most important factor that was associated with the EOL decision (odds ratio - 0.08; 95% confidence interval, 0.01-0.74; P=0.03). Interpretation & conclusions: The documentation of poor prognosis was the only factor found to be associated with EOL care decisions in our study. Prospective, multicentric studies need to be done to evaluate the influence of various other factors on the EOL care.

Study of serial serum myeloid-related protein 8/14 as a sensitive biomarker in Takayasu arteritis: a single centre study.

The aim of the study was to explore utility of serial serum myeloid-related protein 8/14 (MRP8/14) as a biomarker of clinical disease activity and angiographic progression in Takayasu arteritis (TA). Serum MRP8/14 levels were assayed by commercial ELISA for 85 TA patients and 24 healthy controls at baseline, and for 56 and 21 TA patients during follow-up visits R1 and R2, respectively. Disease was categorised as active, indeterminate and stable according to Indian Takayasu Arteritis score (ITAS 2010), ITAS-A(CRP) and angiography. Patients were divided into responders and non-responders/relapsers based on treatment response. Non-parametric tests were used for inter-group comparisons at baseline and during follow-up time points. Generalised Estimating Equation was used to study association between changes in serial MRP8/14 levels and disease activity. At baseline, median MRP8/14 levels were higher in patients with TA than healthy controls [7353 (4524 to11283) vs 4896 (3194 to 8474.5) ng/ml, p = 0.011]. Patients with active disease had higher levels [8552 (5463-12488)] than stable disease [5292.5 (3140.5-7310)], p = 0.002, and healthy controls [4896 (3194-8474.5)], p = 0.001. Changes in serial MRP8/14 level were associated with changes in disease activity, independent of steroid dose, p = 0.000. At R1, MRP 8/14 levels were lower than baseline in responders (n = 38) [9146.0 (6296.8-13693.8) vs 6501 (4314.8-8304.5), p = 0.004], but did not change in non-responders/relapsers (n = 14) [6693.5(4210.8-10516.3) vs 7755.0(5342-10741.0), p = 0.42]. Similar trend was observed at R2. MRP8/14 levels increased during follow-up in 66% and 26.3% of angiographic progressors and non-progressors, respectively. MRP8/14 in TA may act as a novel biomarker with prognostic implications.

Routine placement of subdural drain after burr hole evacuation of chronic and subacute subdural hematoma: a contrarian evidence based approach.

The objective of this paper was to evaluate whether available evidence supporting placement of subdural drain placement after evacuation of chronic subdural haematoma (CSDH) is applicable to a cohort of patients managed by us. In this observational cohort study, clinical follow-up was obtained in 166 patients who underwent burr hole evacuation of CSDH without placement of subdural drain followed by 3 days of bed rest. The primary outcome studied was recurrence requiring reoperation. Factors predicting recurrence were also analysed. We compared the patient characteristics and management protocols in our cohort with that in reports supporting drain placement to determine whether such evidence is relevant to our patient group. The mean age of our patients was 58 ± 17 years (range, 1 to 89 years). Sixteen of the 166 (9.6%) patients presented with symptomatic recurrence. The median time to reoperation for recurrence (15 of 16 patients) after the primary procedure was 17 days (range, 2 to 68 days). Antiplatelet and anticoagulant therapy was the only factor that was significantly associated with recurrence (p = 0.01). There were no infective or non-infective complications in our patient cohort. Our patient cohort and outcomes differed from those reporting drain placements in the following parameters: they were a decade younger, all patients received bed rest for 3 days after surgery and the recurrence rate was similar to that reported in the drained groups but significantly less than that reported in the non-drained groups. Routine placement of drain following burr hole evacuation of CSDH should only be done after careful comparison of the patient cohort under consideration and those reporting superior outcomes with drains. Evidence-based medicine supports such an approach.

Evaluation of reliability and performance of hepatitis B virus-e-antigen assays in tertiary care setting.

Hepatitis B virus-e-antigen (HBeAg) is a viral marker to assess hepatitis B virus (HBV) replication. We have evaluated the reliability of three commonly available HBeAg immunoassays using World Health Organization-International Standard and clinical samples. In addition the performance of enzyme immunoassays (EIAs) was assessed by kinetic binding and reagent exchange experiments. Analytical and diagnostic sensitivity were significantly different among HBeAg assays (P < 0.01). The affinity of capture/detector antibodies varied significantly between EIAs (P < 0.01). Our findings suggest that significant difference in the affinity of capture/detector antibodies to HBeAg may impact the overall performance and the reliability of currently available HBeAg assays in HBV diagnosis and management.

Do turbinate reduction procedures restore epithelial integrity in patients with turbinate hypertrophy secondary to allergic rhinitis? A histopathological study.

PURPOSE: Consensus has not been reached regarding the optimal reduction procedure for inferior turbinate hypertrophy in allergic rhinitis and whether such procedures result in improvement in mucosal architecture. METHODS: Twenty-nine patients aged 18-45 years (mean 26.8 years), with allergic rhinitis and inferior turbinate hypertrophy not responsive to medical therapy who underwent endoscopic submucosal diathermy (ESMD) (14 patients) or endoscopic submucosal resection (ESMR) (15 patients) with intraoperative and 3-6 months postoperative inferior turbinate biopsies, were included in the study. Epithelial and mucosal architecture was compared between the two groups. RESULTS: Both groups showed a significant decrease in epithelial denudation (p < 0.001), reversal of basement membrane thickening (p < 0.001) and increase in density of cilia (p < 0.001). The degree of improvement in histological characteristics between ESMD and ESMR groups was not significant. CONCLUSIONS: Surgical intervention for inferior turbinate hypertrophy by both ESMD and ESMR results in significant restoration of nasal mucosal epithelium in patients with allergic rhinitis as early as 3-month postoperatively. There was, however, no significant difference in the histological changes between those who underwent ESMD and ESMR. CLINICAL TRIALS OF INDIA, REGISTRY NUMBER: CTRI/2015/01/005373.

Accuracy and reliability of Babinski sign versus finger and foot tapping in the diagnosis of corticospinal tract lesions.

INTRODUCTION: The Babinski sign is one of the most important clinical signs for detecting corticospinal tract (CST) lesions. However, due to variations in testing and interpretation, it has been associated with low interobserver agreement rates. In this study, the diagnostic value of finger and foot tapping in detecting CST lesions was compared to that of the Babinski sign. MATERIALS AND METHODS: Three groups of participants were recruited: Group 1 - individuals having CST lesions diagnosed on the basis of clinical examination as well as neuroimaging; group 2 - individuals having a non-CST neurological illness; group 3 - normal individuals who were relatives of the patients recruited. The sensitivity and specificity of finger tapping, foot tapping, and Babinski sign were calculated. RESULTS: 375 patients, 125 in each group, were included. The overall sensitivity for Babinski sign was 49.6% and specificity was 85.8%. The overall sensitivity for finger and foot tapping was 79.5% and specificity was 88.4%. The interobserver agreement between the medical students and the neurologist was greater for finger and foot tapping (Kappa = 0.83) when compared to Babinski sign (Kappa = 0.45). CONCLUSION: Finger and foot tapping is a valid and reliable test in the clinical diagnosis of corticospinal lesions. The reliability and validity of Babinski sign is variable and thus its ability to diagnose the manifestations of corticospinal lesions is less when compared to the finger and foot tapping test.

Randomized double-blind placebo controlled study of preinduction cervical priming with 25 µg of misoprostol in the outpatient setting to prevent formal induction of labour.

OBJECTIVE: To compare the efficacy of preinduction outpatient use of a single dose of 25 µg vaginal misoprostol between 381/2 and 40 weeks with that of placebo, to decrease the interval from intervention to delivery after stretch and sweep in low-risk gravid women with Bishop's score <4. METHOD: Sixty three women received 25 µg vaginal misoprostol and 63 women received placebo after stretch and sweep. RESULTS: The duration from intervention to delivery was 3.35 (1.12-9.46) days in the misoprostol group and 5.42 (2.39-10.11) days in the placebo group which was statistically significant (p = 0.029). Spontaneous labor was seen in 39 women (61.9 %) in the misoprostol group and 35 women (55.6 %) in the placebo group (p = 0.531). Eight women in the misoprostol group and 18 in the placebo group had Lower Segment Caesarean Section (LSCS) and this difference was also statistically significant (p = 0.027). There were no major maternal and neonatal complications in both groups. CONCLUSION: Preinduction use of 25 µg vaginal misoprostol after stretch and sweep in the outpatient setting decreased the intervention to delivery interval when compared to placebo.

INCIDENCE OF, AND RISK FACTORS FOR, MALNUTRITION AMONG CHILDREN AGED 5-7 YEARS IN SOUTH INDIA.

Protein-energy malnutrition is a major health problem contributing to the burden of disease in developing countries. The aim of this study was to assess the incidence of, and risk factors for, malnutrition among school-going children in south India. A total of 2496 children aged 5-7 years from rural and urban areas of south India were recruited in 1982 and followed up for malnutrition over a period of 9 years. Their body heights and weights were measured every six months and socio-demographic factors such as mother's education and father's education and relevant household characteristics and hygiene practices collected. Body mass index and height-for-age z-scores were used to determine children's levels of underweight and stunting, respectively, classified as normal, mild/moderate or severe. Risk factor analysis was done for pre-pubertal ages only using Generalized Estimating Equations with cumulative odds assumption. There was a significant difference between male and female children in the incidence of severe underweight and stunting (6.4% and 4.2% respectively). Children in households with no separate kitchen had 1.3 (1.0-1.6) times higher odds of being severely underweight (p=0.044) compared with those with a kitchen. Children without a toilet facility had significantly higher odds of severe underweight compared with those who did. Children with illiterate parents had higher odds of severe stunting than those with literate parents. In conclusion, the prevalence of malnutrition among these south Indian children has not changed over the years, and the incidence of severe malnutrition was highest in children when they were at pubertal age. The risk factors for stunting were mostly poverty-related, and those for underweight were mostly hygiene-related. Adolescent children in south India should be screened periodically at school for malnutrition and provided with nutritional intervention if necessary.

Cultural adaptation of the Brief COPE for persons living with HIV/AIDS in southern India.

Physical and psychological stressors of HIV infection demand adequate coping responses from persons living with HIV/AIDS (PLHA) and coping strategies may vary by cultural context. The Brief COPE is a well validated scale that has been used extensively to assess coping with cancer, depression, and HIV infection in other settings, but never in India. In this study we translated and validated the 28 item Brief COPE among 299 PLHA in South India, assessing reliability, validity, and cultural appropriateness. Although the original scale demonstrated acceptable internal consistency (alpha = 0.70) and good convergent validity with depression, the test-retest reliability was marginal (test-retest = 0.6) and the original factor structure demonstrated poor fit in a confirmatory factor analysis (CFA). An exploratory factor analysis yielded a 16 item scale with five factors (active planning, social support, avoidant emotions, substance use, religion). A second CFA demonstrated good model fit and acceptable reliability (alpha = 0.61) of the adapted scale.

DOWRY DEMAND AND HARASSMENT: PREVALENCE AND RISK FACTORS IN INDIA.

The practice of dowry is widespread in India and refers to the payment of cash/gifts by the bride's family to the bridegroom's family before marriage. Though prohibited by law, dowry is widely practised, and often contributes to severe injuries and even death of young brides. This study examined the prevalence and risk factors for dowry demand and dowry harassment and its psychosocial correlates across different social strata in India, and also by husband and mother-in-law characteristics. In a cross-sectional survey of 9938 women in rural, urban and urban non-slum sites across India conducted in 1998-99, dowry demand was found to be significantly higher (p<0.001) in the urban non-slum and rural areas (26% and 23% respectively) than in urban slum areas (18%). Overall, 17% of groom's families were not satisfied with the dowry, this being higher in rural areas (21%) than in urban slum and non-slum areas (about 14% in both). The overall prevalence of dowry harassment among this group of women was 13.3%. Mothers-in-law who had themselves experienced dowry demand were 14 (95% CI 5.0-40.4) and 5 (95% CI 1.3-18.9) times more likely to demand and harass daughters-in-law over dowry, respectively. Another significant risk factor for dowry-related harassment was mother-in law's status in the family. Interventions related to modifiable risk factors, such as increased social support at the community level, should help reduce dowry harassment.

Modification of Nurick scale and Japanese Orthopedic Association score for Indian population with cervical spondylotic myelopathy.

AIMS: Existing scales for functional grading of patients with cervical spondylotic myelopathy (CSM), such as the Nurick scale and modified Japanese Orthopedic Association (mJOA) scale, do not address certain culture-specific activities of the Indian population while grading patients with CSM. MATERIALS AND METHODS: We modified the Nurick scale and mJOA scale to develop the Indian modifications of Nurick (imNurick) and mJOA scales (imJOA and imJOA scales), respectively, and then evaluated these modified scales in 93 patients with CSM to determine whether these modifications had a meaningful impact on the functional scores of these patients. RESULTS: There was good interobserver agreement in the assessments documented in all the four scales (Nurick grade, imNurick grade, mJOA scale, and imJOA scale) (kappa = 1). Both Nurick grading (z = 4.4, P = 0.00) and imNurick grading (z = 5.5, P = 0.00) had a valid construct when tested against lower limb mJOA (llmJOA) score. The Indian modified upper limb JOA (imulmJOA) score too had a good construct with modified upper limb JOA (ulmJOA) score (z = 2.5, P = 0.01). There was substantial agreement between Nurick grade and imNurick grade (weighted kappa of 0.75) when taken as a whole group and between ulmJOA score and imulmJOA scores (weighted kappa of 0.75). However, there was significant disagreement between the Nurick grade and imNurick grade scales in patients who were Nurick grade 2 and 3 (kappa = 0.07). CONCLUSIONS: The proposed Indian modifications of Nurick grade and mJOA scale that incorporate the ethnic practices of the Indian population and some Asian population are better discriminators of different levels of functional ability among patients with CSM in this population, as compared to the existing Nurick grading and mJOA scale.

Pharmacokinetics of concentration-controlled mycophenolate mofetil in proliferative lupus nephritis: an observational cohort study.

BACKGROUND: Mycophenolate mofetil (MMF) has variable pharmacokinetics. This study examines the pharmacokinetic and clinical correlations in proliferative lupus nephritis. METHODS: Thirty-four patients were started on MMF, and the area under the concentration-time curve (AUC) was measured by limited sampling strategies, and dosing was adjusted to achieve an AUC of 30-60 mg·h·L. Twenty-seven patients had at least 2 measurements, and renal response was assessed within 1 year. RESULTS: About 61.8% of patients had mycophenolic acid (MPA) AUC <30 mg·h·L with an empiric starting dose of 30 mg/kg. About 79.4% of patients achieved renal response by 1 year, and the median time to renal response was 111 days. MMF dose per body weight had a weak correlation with the AUC and did not correlate with trough concentrations. The median dose was 1.5 g/d at entry and 2 g/d after dose modification during the induction phase. Trough concentrations had a weak correlation with AUC. Patients with serum albumin ≥35 g/L had a greater chance of having an AUC ≥30 mg·h·L. The between-patient coefficient of variability for dose-normalized AUC was 37.9% at entry and 31% within 1 year, whereas repeated measurements over time in an individual had a good intraclass correlation of 0.78. Infections occurred in 11.8% and toxicities in 5.9%. MPA exposure was not significantly associated with adverse events. Patients with an AUC ≥30 mg·h·L had greater renal response at 1 year. CONCLUSIONS: Lupus nephritis patients induced with concentration-controlled MMF had excellent renal response and fewer adverse events with lower than usual dosing. MPA exposure had high interpatient variability, requiring measurements for personalized dosing, and fewer adverse events. Long-term cost reduction is achievable with lower doses and good renal response in the majority of patients.