Madras Medical College

Textbook of pediatric infectious diseases , Textbook of pediatric infectious diseases , کتابخانه دیجیتال جندی شاپور اهواز

Need for developing case definitions and guidelines for data collection, analysis, and presentation for low birth weight as an adverse event following maternal immunization\n\nThe birth weight of an infant is the first weight recorded after birth, ideally measured within the first hours after birth, before significant postnatal weight loss has occurred. Low birth weight (LBW) is defined as a birth weight of less than 2500 g (up to and including 2499 g), as per the World Health Organization (WHO) [1]. This definition of LBW has been in existence for many decades. In 1976, the 29th World Health Assembly agreed on the currently used definition. Prior to this, the definition of LBW was ‘2500 g or less’. Low birth weight is further categorized into very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) [1]. Low birth weight is a result of preterm birth (PTB, short gestation <37 completed weeks), intrauterine growth restriction (IUGR, also known as fetal growth restriction), or both.\n\nThe term low birth weight refers to an absolute weight of <2500 g regardless of gestational age. Small for gestational age (SGA) refers to newborns whose birth weight is less than the 10th percentile for gestational age. This report will focus specifically on birth weight <2500 g. Further details related to case definitions for PTB [2], IUGR and SGA are included in separate GAIA reports.

The recent emergence of coronavirus disease 2019 (COVID-19) pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID-19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID-19. PubMed, EMBASE, and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria. We included five studies reporting CPT to COVID-19 patients. The main findings from available data are as follows: (a) Convalescent plasma may reduce mortality in critically ill patients, (b) Increase in neutralizing antibody titers and disappearance of SARS-CoV-2 RNA was observed in almost all the patients after CPT therapy, and (c) Beneficial effect on clinical symptoms after administration of convalescent plasma. Based on the limited scientific data, CPT therapy in COVID-19 patients appears safe, clinically effective, and reduces mortality. Well-designed large multicenter clinical trial studies should be conducted urgently to establish the efficacy of CPT to COVID-19 patients.

1. The effect of dietary probiotic supplementation on the growth, nitrogen utilisation and serum cholesterol content of broiler chickens was studied in 2 trials. 2. In experiment 1, the birds receiving the 0, 75, 100, 125 mg probiotic/kg diets had weight gains of 1204.0, 1272.0, 1268.3 and 1210.5, respectively at the end of 8 weeks of feeding. The group of birds fed on the 75 mg probiotic supplemented diet retained significantly (P < 0.01) more nitrogen than the control birds. Serum cholesterol content was lower in the probiotic-supplemented birds (93.3 mg/100 ml) compared to the control birds (132.2 mg/100 ml). 3. In the second experiment the probiotic plus antibiotic-supplemented group of birds had the maximum weight gain (1148.5 g) followed by antibiotic (1141.3 g), probiotic-supplemented (1128.4 g) and control birds (1045.6 g) after 6 weeks. Nitrogen retention was greatest in the antibiotic--(48.5%) followed by the probiotic--(46.5%), probiotic plus antibiotic-supplemented groups (46.3%) compared to 40.2% in control birds. 4. The apparent metabolisable energy was greatest in birds receiving the probiotic plus antibiotic-supplemented diet (12.37 MJ/kg) followed by antibiotic--(12.00 MJ/kg), probiotic-supplemented birds (11.92 MJ/kg) than in control birds (11.62 MJ/kg). Serum cholesterol was significantly (P < 0.01) lower in probiotic-supplemented birds (86.1 mg/dl) compared to 118.4 mg/dl in control birds.

We would like to admit that if we were purists, it would prove to be a difficult task to choose between the terms “epidemic” and “hyperendemic” to describe the current alarming situation of increased incidence as well as the prevalence of superficial dermatophytosis in India. For both terms, it would be essential to have comparative epidemiological data of the past and the present, and sadly, we are lacking in both. There is a dire need for well-designed studies as well as more solid evidence for various issues pertaining to the dermatophytosis scenario in India.[1] It is an indisputable fact that there is an increase in the prevalence of dermatophytosis over the past 4–5 years across the country. Comparison of studies done on superficial fungal infections in cities such as Kolkata, Ahmedabad, and Chennai during different time frames have revealed an increasing trend of dermatophytosis.[2,3,4,5,6,7] We, however, need larger epidemiological studies to further bolster our nationwide observation of the alarming increase in its incidence as well as the prevalence.[1] Dermatophytosis has undergone a sea change in its clinical pattern in the past few years. The standard treatment recommendations which we have been following from the Western and Indian literature are no longer valid or even realistic[8,9,10] [Table 1]. In a country like India, where there is a paucity of original studies of dermatophytosis and its treatment, it is becoming amply clear that experience-based treatment of dermatophytosis is ruling the roost and is proving to be more effective than the standard guidelines provided in current literature that one often considers most valid and evidence based. While environmental factors, erratic use of topical and oral antifungal agents, increased prevalence of Trichophyton mentagrophytes infections causing inflammatory lesions and probably a growing resistance to antifungal agents may play an important role, one of the most formidable enemies that we have encountered in the recent times is the irrational fixed drug combination (FDC) creams containing a steroid, antifungal, and antibacterial with three to five molecules in the product.[1,11]Table 1: Treatment schedule of tinea corporisThere are many proponents of topical FDCs containing an antifungal and corticosteroid. An important article highlighting the conclusions of an expert panel meeting on topical treatment of superficial dermatophytoses written after reviewing numerous meta-analyses arrived at some conclusions supporting these combination creams. The authors of this seminal article concluded that adding topical corticosteroid to a topical antifungal agent in the beginning of the therapy can mitigate bothersome inflammation, reduce secondary colonisation with bacteria and enhance the efficacy of the antifungal drug. All the five authors practice in European countries where laws controlling the production and sales of drugs are stringent and are implemented. Therefore, this publication though comprehensive and erudite is not entirely relevant in the Indian context. The authors have specifically mentioned that the corticosteroid may be added in the initial part of the treatment and improper use of the combination creams may lead to both failure of treatment and adverse reactions.[12,13] Both points are very relevant for India. Topical corticosteroids used in combination with antifungal agents are very often potent molecules like clobetasol propionate, they are available over the counter and are grossly abused which includes buying over the counter and applying at will for weeks, months and sometimes years.[1,11,14,15,16,17,18,19] This leads to chronic, treatment resistant dermatophytosis which is causing a havoc in India. This editorial is aimed at highlighting what seems a significant putative role of these FDCs in the dramatic increase in the number of chronic, recurrent, refractory cases of superficial dermatophytosis that we are encountering for the past 4–5 years. A significant temporal association has also been observed between the free availability of irrational FDCs and the epidemic proportion superficial dermatophytosis has assumed. We have categorized this editorial into an elaboration on changing clinical patterns of tinea corporis and tinea cruris which are the most frequently encountered, the effect of freely available irrational FDC creams, the current drug control policies of the government, which the errant companies are taking advantage of and finally some recommendations based on our own experiences and those of several key opinion leaders from India. Changing Clinical Patterns There is a veritable epidemic of steroid modified tinea in India. Topical antifungals used for this condition are most often in combination with potent topical steroids and antibacterials.[1,11] Such formulations account for about 50% of the sales of all topical steroids. The most common combination in India at present is clobetasol propionate, ornidazole, ofloxacin, and terbinafine.[1,11] This speaks volumes about the inadequate understanding of the drug control authorities of India who grant permissions to companies manufacturing them. They cost a mere fraction of pure antifungal creams and hence are very popular. They are often bought over the counter, suggested and sold by the pharmacist or prescribed by the general practitioners. Moreover, they are used erratically, often only for symptom control and that too without any instructions or supervision. People often stop using them when the itching and redness are mitigated and begin to apply again when the symptoms reappear. The cutaneous inflammatory response that the skin mounts to resist and limit the fungal infection is majorly suppressed by topical as well as systemic steroids. However, this effect of topical steroids is said to be more profound than with the other routes. Concomitantly, there is local suppression of T-cell mediated immune response to the dermatophyte. It is this “double trouble” that is most likely responsible for the altered patterns seen increasingly in the past few years. This temporary suppression of the host-induced inflammation leads to ineffective elimination of the dermatophyte, and the process becomes chronic and also widespread. At times, the borders of lesions become unclear resulting in ill-defined and bizarre-shaped lesions. The dermatophyte continues its centrifugal march albeit without adequate central clearing. This phenomenon leads to lesions that insidiously increase in size, adopt unusual shapes including tinea pseudoimbricata, eczematous lesions in the center, etc. It is a common observation that severity of changes in the clinical pattern correlates with the duration of the abuse of topical steroids. The following are observations regarding the most common patterns occurring in India, namely, tinea cruris and tinea corporis: the classic description of lesion of tinea corporis or tinea cruris being circinate with an active erythematous well-defined border and central clearing is no longer valid [Figure 1]. We are seeing an increasing number of atypical presentations, cases that have been vitiated by topical steroids due to the adverse reactions over the treated and surrounding areas and many patients with chronic, recurrent, widespread lesions, many of whom do not respond to standard protocols of therapy. This trend is evident both in private practice as well as in large teaching hospitals. A tertiary care academic department in North India reported a prevalence of about 5%–10% of all new cases, many presenting with recurrent, chronic dermatophytosis with varied clinical presentations.[14]Figure 1: Scaly patch with an erythematous edgeWe are seeing larger sized and greater number of lesions in individual patients [Figure 2a and b]. It is now more common to see patients with more than one lesion of tinea in more than one anatomical location. Tinea cruris et corporis is getting more common.Figure 2: (a and b) Large sized, erythematous patches with active border over the gluteal regions and legsWe are seeing more women with active tinea corporis, tinea cruris, and tinea corporis et tinea cruris. These women often present secondary to the index case that is most often a male. Fashion trends are changing, and tight fitting clothing such as figure hugging denims, leggings, and jeggings are increasingly preferred by youngsters who do not pay heed to practical aspects like their nonsuitability to our hot and humid climate. This could explain the increased prevalence of tinea cruris and tinea corporis not only in overweight but also in otherwise hygiene conscious, young, slim women with no other risk factors. A large number of women present with a submammary location of the infection that involves the inframammary fold more than the skin of the breasts. This underscores the role of friction and maceration resulting from moisture of perspiration. We are also seeing more children with dermatophytosis [Figure 3]. In the past, tinea capitis was considered to be the most common fungal infection occurring in children.[10] Tinea cruris and few small lesions of tinea corporis were uncommonly seen in infants and toddlers being handled by mothers and grandmothers suffering from tinea corporis with lesions on the trunk. In contrast, it is not uncommon now, to see children present with large-sized lesions and involvement of multiple sites. This can be explained by the increased spore load in the families by virtue of multiple family members being affected or perhaps an increased virulence and infectivity of the organism. It is also an indicator of the easy transmissibility of the dermatophyte. The role of fomites seems to be highlighted in the case of children because sharing of beds, linen, and clothing is all too common in them. In the author's experience, obese children are afflicted more. We are seeing a similarity between superficial dermatophytosis and scabies in that both show a distinct familial tendency. This underscores the importance of eliciting a careful family history during all visits. The importance of an untreated and undocumented affected family member being a constant source of reinfection that is often mistaken for treatment failure is being widely recognized in India. The practice of sharing the prescription of one family member with others for the purpose of symptom relief is common, which can also lead to clinical resistance.Figure 3: Tinea faciei in a childWe are seeing an increasing number of lesions with multiple concentric circles. It has also been described as “tinea pseudoimbricata” because it is reminiscent of tinea imbricata characterized by multiple concentric rings and has been explained to be occurring due to partial immune response. It has been seen in persons with immune suppression and those applying corticosteroids.[20] This has been described in India too, after associating its appearance with the use of topical corticosteroid combinations.[21] The authors have suggested that this is included as a of tinea or steroid modified tinea by erratic use of antifungal and topical steroids The of concentric can be explained by the topical corticosteroid local and also its The centrifugal of dermatophytosis is because of the clearing the in the of the lesion and the dermatophyte further at a that is than the of of the to It is that use of would lead to suppression of inflammation and of the dermatophyte which but also in the due to inadequate this it would lead to multiple active borders with clearing in areas where the has been to “tinea one of has used the terms “tinea and “tinea pseudoimbricata” in we the following terms and more at lesions of tinea pseudoimbricata, one that the lesions do not have multiple concentric but very rings and those too are not the which is an important clinical to the of corticosteroid modified tinea is more and to for care [Figure and There is also a between the terms “tinea and modified We the “tinea be used only in cases where the is due to its altered most due to topical However, in most cases of superficial dermatophytosis in which topical steroids and their irrational have been it is to the fungal Therefore, modified is a more it is the “tinea is and be “tinea (a and b) in the and mentioned a large number of lesions do not show central clearing. there are the lesions of tinea cruris and tinea corporis [Figure explained in the of tinea pseudoimbricata, the central could be due to inadequate clearing of the to topical steroid and the inflammatory response that the would in those patch a lesion of tinea see lesions, an increasing number of multiple lesions of various the tinea by the of large lesions with and at times a of multiple small lesions with active erythematous borders [Figure lesions show borders [Figure The has been to a virulence of the a inflammatory erythematous and lesions with in the to a large lesions with erythematous borders by of large lesions. Tinea lesion with distinct of dermatophytosis which seems to have been and the more of tinea cruris is There have been of tinea written over in which Indian authors have observed it frequently there have been of the from There has been a paucity of recent literature from India on dermatophytosis one written by the and which the current increase in tinea the of steroid dermatophytosis is observed to be seen more in and more on the than the It is by tinea cruris or tinea cruris et corporis treated by irrational it in it the and While lesions with classic active borders may be seen on the some like areas of ill-defined lesions and are also seen [Figure and b]. these patients have lesions on the of the that are by as well as on the and [Figure The aspects of the too may be affected [Figure This it essential to the by it from the which too may be affected The be in a that the lesions, often of tinea cruris, do not this to the often in inadequate treatment because of the The untreated lesions become a of a chronic infection to (a and b) Scaly patch over the of The aspects of the too may be patch over the of the number of tinea faciei are being of these patients have an infection of other areas such as tinea corporis or tinea cruris. of these cases of tinea faciei are probably of tinea because it is often difficult to the active borders of these lesions [Figure However, the of the affected is often as has been reported in tinea capitis in children as Tinea tinea are said to be more number of cases of tinea and these have been to be an from the or the and is as of tinea which is the most common of tinea capitis in [Figure of tinea capitis in an are seeing more of of tinea corporis, where there is widespread involvement of with with of these patients are of the have of topical steroid abuse the lesions of dermatophytosis as well as in their The most frequently seen in steroid modified tinea are and [Figure it is the that show the have we seen many dramatic of by topical steroids. They sometimes as as of of FDCs containing and potent steroid molecules such as clobetasol a of them and even with Moreover, it is to see patients to apply the to the to a patients are seen with a of active of the skin with resulting from steroid over the areas over both the also and seen with erythematous tinea corporis and tinea cruris due to the topical steroid fact is the that superficial dermatophytosis on the and there are multiple family members and for effective treatment, member has to a and drugs of their own This is often a to many for who drugs only for one member and with them for other members by taking for which further the Changing of In the recent there seems to be an epidemiological of in India. many studies done across India have Trichophyton to be the most common the prevalence is to the In all these Trichophyton mentagrophytes has as the with an increased prevalence in to what was seen in the A in the of the of has also been studies across the country have Trichophyton mentagrophytes to be the This has been to a in the This change may be responsible for the widespread and inflammatory lesions that mentagrophytes is This change also the we the role of fomites in of In an for on a mentagrophytes for on This fact the importance of of which could be done by in hot at and in as is considered to be the most effective for antifungal resistance to be the most important for the treatment failure of the it is essential for to few about antifungal the of which has to be considered for antifungal and for fungal resistance is into resistance and clinical resistance to of a to an antifungal agent as by in in which the the for that organism. resistance can be or secondary or the resistance without to the drug as is the resistance of to and to or the resistance which after to the antifungal agent is on altered This is by resistance and Clinical resistance is the failure to a fungal infection the of an antifungal agent which may or may not in the resistance for that organism. Clinical resistance may be due to a combination of to the the or the antifungal There have been few of resistance of to and antifungal for the are to than the antibacterial they are by At present, standard guidelines have been by the Clinical and European on for in antifungal of of by and is as the standard of is as the of an antifungal agent that will the of antifungal resistance is with increased do not with clinical response to antifungal The between the in and in resistance in has been by the which that that infections due to respond to therapy in of cases, infections due to resistant respond in of also as are used to and resistance to antifungal agents, as the of They are categorized as and However, now, the have not been for the due to of data on the clinical or epidemiological that it is to not to use the in the of these for this increase in the of to and observed in various studies not that there is an this only the use of adequate or of these drugs or a longer duration of treatment to the clinical response. scenario for antifungal studies across the country to the pattern and any increase in of the of for by the The the observations and in the recent editorial in the regarding the dire need for more studies and a evidence for the and treatment recommendations of the current epidemic of superficial dermatophytosis in The of Topical and Topical steroids of all or in combination with other have for all practical been sold over the counter because of laws to different The of India finally heed to the constant and recommendations of Indian of and in and included most topical steroid molecules as drugs they be sold over the counter and without a valid prescription of a However, the to this effect in the of has not been and all topical steroids to be sold freely in the The in also many irrational and available topical FDCs containing an antifungal, steroid, and antibacterial the have in a in a of India and they to be and sold with It is that no has been to to many irrational A of this of topical drugs is the FDC containing ofloxacin, and other which are and of a topical antifungal, an and a steroid are freely available in the and have become the of Indian The and authorities have also permissions to irrational with a to antifungal resistance such as topical and oral FDCs containing and These permissions as irrational and a the fact that the is to resistance We would like to relevant key from the fact by as as is an increasingly to that across all and cost of care for patients with resistant infections is than care for patients with infections due to longer duration of and use of more All new drugs and their are by to their and efficacy data to the if data pertaining to such FDCs have been at all and if on what and with what understanding of has the them. It is common that often authorities permissions without the or of the a of and in a that with the of the Treatment We are seeing a sea change in the prescription patterns of in private practice as well as in academic The guidelines of do not We are using of oral antifungals for a longer time and these to the patients more. we have observed that even topical antifungal creams need to be for a longer the oral or topical therapy is often with a of lesions or even new lesions in other of of oral as well as topical antifungal drugs are available in India. We have observed that many by companies often do not have efficacy when to of It would be a of of various It is also to see drug companies to to antifungal formulations such as as well as and of and of of a of for and for or for is to be more [Table 1]. the antifungal agents such as in a of a for or in a of for to lead to a clinical in patients with However, it is important to and and a one the use of systemic antifungals in a the in patients who are on multiple The recommendations by three of the most of in India in do not relevant in We need treatment guidelines based on Indian experiences that are by our own A large number of for the of of for and are of the drug for or more and have observed clinical response. topical antifungals such as and are to be more to the like probably because they The is that all these changes in pattern of are even if to the of the without a in most patients in the case of private who the of it is to be essential in many it is not practical because it is time and most often the do not have to do While the initial of dermatophytosis not in there is a need for the the treatment with the oral antifungals in case of partial The following are to be by of any antifungal a steroid is highlighting the of these FDCs is on the importance of of and to the of the The topical antifungals be the of the lesion for at clinical We this of applying topical antifungals the a for clinical of tight such as leggings, and jeggings sharing of if and of and only after the and in hot and them. is to In the of the would be too of well after about of if is not patients with tinea cruris to of the tight fitting that the and into it etc. or the by with as to reduce the spore load in the all this is however, it is to the and to enhance the of the We could or use to the to all these The and the We need to and the fact that there is a of and evidence in that we have regarding this epidemic of superficial dermatophytosis in India. The are studies proving the association of topical the and chronic widespread which is a task for We are beginning to the resistance if by antifungal We need to into more aspects and aspects that are to lead to chronic widespread dermatophytosis However, it is clear that the of topical steroids has to be The easy availability of and containing and antifungals has to be Topical steroids and their need to be sold as The will most likely resistance from but the has to be with for we see a in steroid modified tinea and many cases of chronic widespread The in and all authorities need to the of an expert panel of to new They need to the has to and about this The association has also several to the and other in the of and FDCs and formulations are also to many It is that the one of the in manufacturing as well as is responsible for this situation which could have been of The authors that they have all In the the for and other clinical to be reported in the The patients that their and will not be and due will be to their but be

BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

BACKGROUND: Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment. METHODS: This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD. FINDINGS: Globally, in 2023, 788 million (95% uncertainty interval 743-843) people aged 20 years and older were estimated to have CKD, up from 378 million (354-407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4-15·2), a relative rise of 3·5% (2·7-4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9-19·4). Most people had stage 1-3 CKD, with a combined prevalence of 13·9% (13·1-15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30-1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8-857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4-14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. INTERPRETATION: CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes. FUNDING: Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.

The disease burden of chronic-relapsing and therapy-refractory superficial dermatophytosis dramatically increased in India within the past 5-6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR-ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)-1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte-positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR-ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte-positive showing 151 (93.21%) T mentagrophytes- and 11 (6.79%) T rubrum-positive samples. In this study, we show for the first time a dramatic Indian-wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes "Indian ITS genotype" that might be disseminated Indian-wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.

The case of eighty-one patients who had tuberculosis of the spine that was treated by debridement and anterior arthrodesis were reviewed eight years or more postoperatively. We studied the progression of the kyphosis and evaluated the function and fate of the bone grafts that were used. At eight years, the results with respect to the progression of the kyphosis were classified as excellent or good in forty-eight patients (59 per cent), all of whom had had minimum destruction of the vertebral bodies; limited surgical excision of bone, resulting in a small post-debridement defect that needed only a short graft; marked intraoperative correction of the deformity; and involvement of lower lumbar segments. Fifteen patients (19 per cent) had a fair result and eighteen (22 per cent), a poor result. An increase in the deformity was common in patients who had extensive involvement of the vertebral bodies that had resulted in a large post-debridement defect necessitating a graft spanning more than two disc spaces. Lesions of the thoracic vertebrae were associated with many of the poor results, and patients who had a marked kyphosis before treatment also did not do well. A stable graft that provided structural support was observed in only thirty-three patients (41 per cent), and failure of the graft due to slippage, fracture, absorption, or subsidence was seen in forty-eight patients (59 per cent). The length of the graft also played a role: the graft failed most often in patients in whom it spanned more than two disc spaces. We concluded that it is unwise to rely solely on the graft to prevent vertebral collapse in patients in whom the length of the graft exceeds two disc spaces. These patients may benefit from additional measures, such as an extended period of non-weight-bearing, posterior arthrodesis after six to twelve weeks, and prolonged use of a brace until complete consolidation is evident.

BACKGROUND: Dermatophytosis management has become an important public health issue, with a large void in research in the area of disease pathophysiology and management. Current treatment recommendations appear to lose their relevance in the current clinical scenario. The objective of the current consensus was to provide an experience-driven approach regarding the diagnosis and management of tinea corporis, cruris and pedis. METHODS: Eleven experts in the field of clinical dermatology and mycology participated in the modified Delphi process consisting of two workshops and five rounds of questionnaires, elaborating definitions, diagnosis and management. Panel members were asked to mark "agree" or "disagree" beside each statement, and provide comments. More than 75% of concordance in response was set to reach the consensus. RESULT: KOH mount microscopy was recommended as a point of care testing. Fungal culture was recommended in chronic, recurrent, relapse, recalcitrant and multisite tinea cases. Topical monotherapy was recommended for naïve tinea cruris and corporis (localised) cases, while a combination of systemic and topical antifungals was recommended for naïve and recalcitrant tinea pedis, extensive lesions of corporis and recalcitrant cases of cruris and corporis. Because of the anti-inflammatory, antibacterial and broad spectrum activity, topical azoles should be preferred. Terbinafine and itraconazole should be the preferred systemic drugs. Minimum duration of treatment should be 2-4 weeks in naïve cases and > 4 weeks in recalcitrant cases. Topical corticosteroid use in the clinical practice of tinea management was strongly discouraged. CONCLUSION: This consensus guideline will help to standardise care, provide guidance on the management, and assist in clinical decision-making for healthcare professionals.

OBJECTIVE: To assess the impact of supplementing newborn infants with vitamin A on mortality at age 6 months. DESIGN: Community based, randomised, double blind, placebo controlled trial. SETTING: Two rural districts of Tamil Nadu, southern India. PARTICIPANTS: 11 619 newborn infants allocated 24 000 IU oral vitamin A or placebo on days 1 and 2 after delivery. MAIN OUTCOME MEASURE: Primary outcome measure was mortality at age 6 months. RESULTS: Infants in the vitamin A group had a 22% reduction in total mortality (95% confidence interval 4% to 37%) compared with those in the placebo group. Vitamin A had an impact on mortality between two weeks and three months after treatment, with no additional impact after three months. CONCLUSION: Supplementing newborn infants with vitamin A can significantly reduce early infant mortality.

1. The effect of probiotic supplementation on egg production, on serum and yolk cholesterol and on egg shell thickness in 24 White Leghorn layers was studied from 28-38 weeks of age. 2. In 3 treatments the diet was supplemented with 0, 100 and 150 mg probiotic/kg food. 3. In the 100 mg probiotic group, egg production improved by 5%, and shell thickness improved slightly, with fewer thin-shelled eggs than in the control (8.6% compared to 18.6%). 4. The initial serum cholesterol concentration of 170.2 mg/dl in control birds remained similar throughout the 10-week experimental period, whereas in the 150 mg group the initial value of 176.5 mg/dl decreased to 114.3 mg by week 10. 5. Yolk cholesterol concentration was 14.69 mg in the control group and 11.28 and 11.37 mg/g in the 100 and 150 mg probiotic groups respectively. Overall mean total egg cholesterol was thus reduced by probiotic supplementation.

BACKGROUND: The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. METHODS: Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. RESULTS: C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). CONCLUSIONS: C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

We examined the presence and co-occurrence of psychosocial health conditions (depression, frequent alcohol use, and victimisation) among men who have sex with men (MSM) and transgender (TG) women in India, and their cumulative association with sexual risk. A survey questionnaire was administered among a convenience sample of 600 participants (MSM = 300; TG women = 300) recruited through six non-governmental organisations in four states. Prevalences of the number of psychosocial health conditions among MSM were: none = 31.3%, one = 43%, two = 20%, and three = 5.7%; and among TG women: none = 9%; one = 35.33%, two = 38.33%, and three = 17.33%. In bivariate and multivariate models, these conditions were positively and additively related to sexual risk, providing evidence for a syndemic of psychosocial health conditions among MSM and TG women and their synergistic effect on sexual risk. In addition to the number of syndemic conditions, resilient coping and social support were significant predictors of sexual risk among MSM and TG women, respectively. HIV preventive interventions in India should screen for and address co-occurring psychosocial health conditions - experiences of violence, mental health issues, and alcohol use - among MSM and TG women.

In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan.

CONTEXT: Chronic pancreatitis is common in India. However, its risk factors are not clear. There is sparse data on the current prevalence of tropical pancreatitis in India. OBJECTIVE: To undertake a prospective nationwide study of the risk factors and clinical profile of chronic pancreatitis. SETTING: Thirty-two major centers from different regions of India contributed data on 1,086 patients to a common online website (www.ipans.org). MAIN OUTCOME MEASURES: Risk factors, clinical features complications and treatment of chronic pancreatitis. RESULTS: Of the 1,086 subjects, complete data on risk factors were available for 1,033 subjects. Idiopathic pancreatitis was the most common form of pancreatitis (n=622; 60.2%) and alcoholic chronic pancreatitis accounted for about a third of the cases (n=400; 38.7%); the rest (n=11; 1.1%) had rare risk factors. Smoking and cassava intake were documented in 292 (28.3%) and 189 (18.3%) subjects, respectively. Using well-defined criteria, only 39 (3.8%)cases could be labeled as 'tropical pancreatitis'. Pain occurred in 971 patients (94.0%). Four hundred and eighteen (40.5%) subjects had diabetes mellitus. Of alcohol consumers, alcoholism and female gender were independent risk factors for diabetes in subjects with chronic pancreatitis (OR=1.48, P=0.003; and OR=1.75, P<0.001, respectively). The most common complications were pseudocysts (15.8%) and biliary obstruction (8.2%). Pancreatic cancer occurred in 42 subjects (4.1%). Ultrasound detected calculi in 69.7%, ductal dilatation in 63.4% and atrophy in 27.3%. The majority of patients were on medical therapy (n=849; 82.2%); endotherapy and surgery accounted for the rest. About 50% percent of the patients with diabetes required insulin (198/418). CONCLUSIONS: In this first nationwide prospective survey of chronic pancreatitis in India, idiopathic pancreatitis was the most common form, followed by alcoholic pancreatitis. The classical form of tropical chronic pancreatitis is becoming less common.

This is a qualitative study of 76 women with schizophrenia whose marriages had broken. The sample was drawn from three different centres. Using qualitative methods of exploration, information regarding their illness, the marriage and its separation and the various consequences of this event was gathered. Many of them had not separated legally and were not receiving any maintenance from their husbands. Their concerns centred around their future, the fact they would be a burden to their ageing parents and in some cases about their children. Stigma attached to separation was as poignant as that of being mentally ill, if not more. However, a striking aspect was that even after several years of separation, these women still harboured a lot of hope that they would be able to reunite with their husbands.

RAMAKRISHNAN, K. MATHANGI F.R.C.S. (ENG.); THOMAS, K. POTHAN M.S.; SUNDARARAJAN, CHEYYUR R. M.S. Author Information

The paper describes the two-year follow-up results from 323 out of 386 patients fulfilling a modified version of Feighner's criteria for diagnosis of schizophrenia, in Lucknow, Vellore, and Madras. There was remission in 66% of cases. Short duration of illness, consistent compliance with medication, positive attitudes of relatives and neighbours, absence of economic difficulties, increase in religious activities on the part of patients, a rural background, and a non-schizoid pre-morbid personality were associated with good outcome. Features of depression, dangerous behaviour, and absence of agitation were associated with poor outcome.