Effects of responsive stimulation and nutrition interventions on children\u27s development and growth at age 4 years in a disadvantaged population in Pakistan: a longitudinal follow-up of a cluster-randomised factorial effectiveness trial

Background: A previous study in Pakistan assessed the effectiveness of delivering responsive stimulation and enhanced nutrition interventions to young children. Responsive stimulation significantly improved children\u27s cognitive, language, and motor development at 2 years of age. Both interventions significantly improved parenting skills, with responsive stimulation showing larger effects. In this follow-up study, we investigated whether interventions had benefits on children\u27s healthy development and care at 4 years of age.Methods: We implemented a follow-up study of the initial, community-based cluster-randomised effectiveness trial, which was conducted through the Lady Health Worker programme in Sindh, Pakistan. We re-enrolled 1302 mother-child dyads (87% of the 1489 dyads in the original enrolment) for assessment when the child was 4 years of age. The children were originally randomised in the following groups: nutrition education and multiple micronutrient powders (enhanced nutrition; n=311), responsive stimulation (n=345), combined responsive stimulation and enhanced nutrition (n=315), and routine health and nutrition services (control; n=331). The data collection team were masked to the allocated intervention. The original enrolment period included children born in the study area between April 1, 2009, and March 31, 2010, if they were up to 2·5 months old without signs of severe impairments. The primary endpoints for children were development and growth at 4 years of age. Interventions were given in monthly group sessions and in home visits. The primary endpoint for mothers was wellbeing and caregiving knowledge, practices, and skills when the child was 4 years of age. Analysis was by intention to treat. The original trial is registered with ClinicalTrials.gov, number NCT00715936.Findings: 1302 mother-child dyads were re-enrolled between Jan 1, 2013, and March 31, 2013, all of whom were followed up at 4 years of age. Children who received responsive stimulation (with or without enhanced nutrition) had significantly higher cognition, language, and motor skills at 4 years of age than children who did not receive responsive stimulation. For children who received responsive stimulation plus enhanced nutrition, effect sizes (Cohen\u27s d) were 0·1 for IQ (mean difference from control 1·2, 95% CI -0·3 to 2·7), 0·3 for executive functioning (0·18, -0·07 to 0·29), 0·5 for pre-academic skills (7·53, 5·14 to 9·92) and 0·2 for pro-social behaviours (0·08, 0·03 to 0·13). For children who received responsive stimulation alone, effect sizes were 0·1 for IQ (mean difference with controls 1·7, -0·3 to 3·7), 0·3 for executive functioning (0·17, 0·07 to 0·27), 0·2 for pre-academic skills (3·86, 1·41 to 6·31), and 0·2 for pro-social behaviours (0·07, 0·02 to 0·12). Enhanced nutrition improved child motor development, with effect size of 0·2 for responsive stimulation plus enhanced nutrition (0·56, -0·03 to 1·15), and for enhanced nutrition alone (0·82, 0·18 to 1·46). Mothers who received responsive stimulation (with or without enhanced nutrition) had significantly better responsive caregiving behaviours at 4 years of child age than those who did not receive intervention. Effect size was 0·3 for responsive stimulation plus enhanced nutrition (1·95, 0·75 to 3·15) and 0·2 for responsive stimulation (2·01, 0·74 to 3·28). The caregiving environment had a medium effect size of 0·3 for all interventions (responsive stimulation plus enhanced nutrition 2·99, 1·50 to 4·48; responsive stimulation alone 2·82, 1·21 to 4·43; enhanced nutrition 3·52, 1·70 to 5·34).Interpretation: Responsive stimulation delivered in a community health service can improve child development and care, 2 years after the end of intervention. Future analyses of these data are needed to identify which children and families benefit more or less over time.FUNDING: Grand Challenges Canada

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Laparoscopic cholecystectomy in empyema of gall bladder: An experience at Liaquat University Hospital, Jamshoro, Pakistan

Objective: To find out the safety profile of laparoscopic cholecystectomy in empyema of gallbladder. Background: Empyema of gall bladder is a severe form of acute cholecystitis with superadded suppuration. It has been considered a contraindication for the laparoscopic cholecystectomy (LC) because of fear of life-threatening complications. This study aimed to determine the safety and feasibility of LC in empyema of gallbladder. Materials and Methods: LC was attempted in 67 patients of empyema of gallbladder within 24h. However in few cases there was a delay because of reluctance for surgery or delay in giving consent etc. The procedure was performed by standard four-port technique with few changes made to facilitate dissection according to situation. Results: Between April 2003 to June 2006, 970 LC performed for gallstone disease at surgical unit-1 of LUMHS by the same surgical team. Among these, 67 (6.90%) patients were diagnosed to have empyema gall bladder. LC successfully completed in 54 (80.59%) patients. In 13 (19.40%) patients the procedure was converted to open cholecystectomy (OC) due to various operative difficulties of which the most serious injuries included bleeding from cystic artery (four cases), common bile duct injury (two cases) and duodenal injury in one case. Maximum operating time was up to 160 minutes (one case). Postoperative complications occurred in 10 (18.51%) successfully operated patients. Maximum patients (n=45, 83.33%) were discharged in 48-96 hours while three patients were discharged after two weeks. Conclusion : Laparoscopic cholecystectomy can be performed in empyema of gallbladder keeping in mind a slightly increased risk of complications even in the best hands. However, the experience of the surgeon plays a key role in the overall outcome

Effects of responsive stimulation and nutrition interventions on children's development and growth at age 4 years in a disadvantaged population in Pakistan: a longitudinal follow-up of a cluster-randomised factorial effectiveness trial

Background: A previous study in Pakistan assessed the effectiveness of delivering responsive stimulation and enhanced nutrition interventions to young children. Responsive stimulation significantly improved children's cognitive, language, and motor development at 2 years of age. Both interventions significantly improved parenting skills, with responsive stimulation showing larger effects. In this follow-up study, we investigated whether interventions had benefits on children's healthy development and care at 4 years of age. Methods: We implemented a follow-up study of the initial, community-based cluster-randomised effectiveness trial, which was conducted through the Lady Health Worker programme in Sindh, Pakistan. We re-enrolled 1302 mother–child dyads (87% of the 1489 dyads in the original enrolment) for assessment when the child was 4 years of age. The children were originally randomised in the following groups: nutrition education and multiple micronutrient powders (enhanced nutrition; n=311), responsive stimulation (n=345), combined responsive stimulation and enhanced nutrition (n=315), and routine health and nutrition services (control; n=331). The data collection team were masked to the allocated intervention. The original enrolment period included children born in the study area between April 1, 2009, and March 31, 2010, if they were up to 2·5 months old without signs of severe impairments. The primary endpoints for children were development and growth at 4 years of age. Interventions were given in monthly group sessions and in home visits. The primary endpoint for mothers was wellbeing and caregiving knowledge, practices, and skills when the child was 4 years of age. Analysis was by intention to treat. The original trial is registered with ClinicalTrials.gov, number NCT00715936. Findings: 1302 mother–child dyads were re-enrolled between Jan 1, 2013, and March 31, 2013, all of whom were followed up at 4 years of age. Children who received responsive stimulation (with or without enhanced nutrition) had significantly higher cognition, language, and motor skills at 4 years of age than children who did not receive responsive stimulation. For children who received responsive stimulation plus enhanced nutrition, effect sizes (Cohen's d) were 0·1 for IQ (mean difference from control 1·2, 95% CI −0·3 to 2·7), 0·3 for executive functioning (0·18, −0·07 to 0·29), 0·5 for pre-academic skills (7·53, 5·14 to 9·92) and 0·2 for pro-social behaviours (0·08, 0·03 to 0·13). For children who received responsive stimulation alone, effect sizes were 0·1 for IQ (mean difference with controls 1·7, −0·3 to 3·7), 0·3 for executive functioning (0·17, 0·07 to 0·27), 0·2 for pre-academic skills (3·86, 1·41 to 6·31), and 0·2 for pro-social behaviours (0·07, 0·02 to 0·12). Enhanced nutrition improved child motor development, with effect size of 0·2 for responsive stimulation plus enhanced nutrition (0·56, −0·03 to 1·15), and for enhanced nutrition alone (0·82, 0·18 to 1·46). Mothers who received responsive stimulation (with or without enhanced nutrition) had significantly better responsive caregiving behaviours at 4 years of child age than those who did not receive intervention. Effect size was 0·3 for responsive stimulation plus enhanced nutrition (1·95, 0·75 to 3·15) and 0·2 for responsive stimulation (2·01, 0·74 to 3·28). The caregiving environment had a medium effect size of 0·3 for all interventions (responsive stimulation plus enhanced nutrition 2·99, 1·50 to 4·48; responsive stimulation alone 2·82, 1·21 to 4·43; enhanced nutrition 3·52, 1·70 to 5·34). Interpretation: Responsive stimulation delivered in a community health service can improve child development and care, 2 years after the end of intervention. Future analyses of these data are needed to identify which children and families benefit more or less over time. Funding: Grand Challenges Canada

Household food access and child malnutrition: Results from the eight-country MAL-ED study

Background: Stunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites.Methods: We administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites.Results: Average age of study children was 41 months. Mean food access insecurity score (range: 0-27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17).Conclusions: Our study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition

Progesterone Inhibits Basal and Gonadotropin-Releasing Hormone Induction of Luteinizing Hormone β-Subunit Gene Expression

LH and FSH play critical roles in mammalian reproduction by mediating steroidogenesis and gametogenesis in the gonad. Gonadal steroid hormone feedback to the hypothalamus and pituitary influences production of the gonadotropins. We previously demonstrated that progesterone differentially regulates the expression of the LH and FSH β-subunits at the level of the gonadotrope: FSHβ transcription is induced, whereas LHβ is repressed. In this study, we investigated the mechanism of progesterone repression of LHβ gene expression using immortalized gonadotrope-derived LβT2 cells. The progesterone suppression of both basal and GnRH-induced LHβ gene expression occurs in a hormone- and receptor-dependent manner. Chromatin immunoprecipitation demonstrates that the hormone-bound progesterone receptor (PR) is recruited to the endogenous mouse LHβ promoter. In addition, suppression requires both the amino-terminal and DNA-binding regions of PR. Furthermore, progesterone suppression does not require direct PR binding to the promoter, and, thus, PR is likely recruited to the promoter via indirect binding through other transcription factors. These data demonstrate that the molecular mechanism for progesterone action on the LHβ promoter is distinct from FSHβ, which involves direct PR binding to the promoter to produce activation. It also differs from androgen repression of LHβ gene expression in that, rather than Sp1 or steroidogenic factor-1 elements, it requires elements within −300/−250 and −200/−150 that also contribute to basal expression of the LHβ promoter. Altogether, our data indicate that progesterone feedback at the level of the pituitary gonadotrope is likely to play a key role in differential production of the gonadotropin genes

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable