Enhanced autophagy and phagocytosis of apoptotic lymphocytes in splenic macrophages of acute ethanol-treated rats: Light and electron microscopic studies.

Autophagy is a prosurvival mechanism for the clearance of damaged cellular components, specifically upon exposure to various stressors. In lymphoid organs, excessive ethanol consumption increases lymphocyte apoptosis, resulting in immunosuppression. However, ethanol-induced autophagy and related phagocytosis of apoptotic lymphocytes in the spleen have not been studied yet. Adult male Wistar rats were injected intraperitoneally either with 5 g/kg ethanol or phosphate-buffered saline (as a control group) and then sacrificed 0, 3, 6, and 24 hours after injection. Light and transmission electron microscopy (TEM) findings indicated enhanced T cell apoptosis in the white pulps of ethanol-treated rats (ETRs) compared with the control group, which peaked at 6 h and was associated with the accumulation of tingible body macrophages (TBMs). These macrophages exhibited an upregulated autophagic response, as evidenced by enhanced LC3-II (a specific marker of autophagosomes) expression, which peaked at 24h. In addition, double labeling immunofluorescence of LC3-II with lysosomal markers revealed the enhanced formation of autolysosomes in TBMs of ETRs, which was associated with suppression of p62 immunostaining, indicating the enhanced autophagic flux. Interestingly, this elevated autophagic response in ETR TBMs was accompanied by evidence of LC3-associated phagocytosis (LAP) of apoptotic splenocytes. This is based on TUNEL/LC3-II double labeling and TEM observations of phagosomes containing apoptotic bodies, enclosed within phagosomal membranes adjacent to the autophagic vacuoles. It can be concluded that enhanced prosurvival autophagy in splenic TBMs of ETRs and clearing of apoptotic lymphocytes via LAP may contribute to preventing secondary necrosis and autoimmune diseases.

Biallelic Variants in Seven Different Genes Associated with Clinically Suspected Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the IFT27 (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the WDPCP (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the MKKS/BBS5 (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in BBS1 (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in BBS1 (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in MKKS (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in BBS5 (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders.

Emerging mechanistic insights of selective autophagy in hepatic diseases.

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria (via mitophagy), and lipid droplets (LDs; via lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses (via virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases. For example, lipophagy has emerged as a defensive mechanism against chronic liver diseases. There is a prominent role for mitophagy and lipophagy in hepatic pathologies including non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and drug-induced liver injury. Moreover, these selective autophagy pathways including virophagy are being investigated in the context of viral hepatitis and, more recently, the coronavirus disease 2019 (COVID-19)-associated hepatic pathologies. The interplay between diverse types of selective autophagy and its impact on liver diseases is briefly addressed. Thus, modulating selective autophagy (e.g., mitophagy) would seem to be effective in improving liver diseases. Considering the prominence of selective autophagy in liver physiology, this review summarizes the current understanding of the molecular mechanisms and functions of selective autophagy (mainly mitophagy and lipophagy) in liver physiology and pathophysiology. This may help in finding therapeutic interventions targeting hepatic diseases via manipulation of selective autophagy.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

Current Scenario and Future Direction of Newborn Screening and Management Program for Phenylketonuria in Bangladesh

Abstract Phenylketonuria (PKU) is a correctable inborn error of metabolism which causes lethal intellectual delay and neurobehavioral anomalies. A screening package, especially for early recognition can support to regulate the PKU process of most patients. New-born screening program in any country focuses at the earliest detection of inheritance deficiency disorders in order to avoid the most severe repercussion by appropriate medication. This screening program needs a concomitant diagnosis and involves additional clinical research. Strategies from developed countries recommend that new-born screening should be done as soon as possible after birth before hospital/clinic discharge because if detected later, it conveys to significantly increase in disability as well as morbidity. Although exact protocol differs among different countries, testing procedures for PKU should be followed universally recognized in the developed world. Unfortunately, new-born screening program in Bangladesh is in lying-in room or possibly in pilot study in particular hospital, because the health-care system is classically targeted mortality (like childbirth complications) and transmittable morbidities (such as COVID-19) but not inborn frailties. Although policies and management of childbirth complications have been successfully lowered infant and mother mortality rates, the number of disabled babies increased tremendously. The study aims to investigate the current status of new-born screening (NBS) program of PKU in the Rajshahi Division Bangladesh, and focus on future plans to manage with life-long treatment. The primary challenges such as financial support for newborn screening, publicity, should be identified and implemented for national PKU-NBS policy as a role model of Bangladesh for developing countries.

Cold storage-mediated rearing of Trichogramma evanescens Westwood on eggs of Plodia interpunctella (Hübner) and Galleria mellonella L.

The egg parasitoid Trichogramma evanescens Westwood is considered as an efficient biological control agent for managing several lepidopteran pests and it is widely distributed throughout the world. Mass rearing protocols of parasitoids that are currently in use in biocontrol programs require a meticulous quality control plan, in order to optimize their efficacy, but also their progeny production capacity. In this paper, the effect of different factors on the quality control in mass rearing of T. evenescens, using Plodia interpunctella (Hübner) and Galleria mellonella L. as host species, were investigated. The impact of egg agewas significant in the rates of parasitism, for both host species tested. Significantly highest percent of parasitoid emergence was noticed in two day-old eggs for both host species, while one day-old eggs day exhibited the maximum emergence when both species were used togetherin the same trials. Age-dependent storage egg preservation at either 4 or 9°C significantly influenced the parasitism percentages on both species. The highest parasitism percentage was recorded in two day-old G. mellonella eggs that are kept for 15 days at 9°C while the lower in one day-old P. interpunctella eggs for 60 d storage. Moreover, the highest parasitoid mortality was recorded in T. evanescens reared either on P. interpunctella or G. mellonella at 20°C. Rearing of the parasitoid on a mixture of eggs of both host species resulted in higher parasitism, but not always in higher rates of parasitoid emergence. The results of the present work provide useful information that can be further utilized in rearing protocols of T. evanescens.

Is Suprascapular Nerve Block Better Than Intra-articular Corticosteroid Injection for the Treatment of Adhesive Capsulitis of the Shoulder? A Randomized Controlled Study.

BACKGROUND: Adhesive Capsulitis of shoulder (AdCS) is a treatment dilemma for surgeons. Intraarticular Corticosteroid Injection (IACI) has shown only short-term benefit in improving shoulder-related disability. Suprascapular nerve block (SSNB) has shown promise in trials in reducing chronic shoulder pain. Thus a RCT was conducted to compare the efficacy of SSNB versus IACI in the treatment of AdCS. MATERIAL AND METHODS: 86 patients with AdCS were divided into SSNB and IACI groups by block randomization. SSNB group received single Suprascapular Nerve Block with 10ml of 0.5% Bupivacaine while IACI group received single injection of 40mg Triamcinolone and 1ml 2% Lignocaine in the shoulder; both followed by physiotherapy and followed-up and evaluated with SPADI and modified Constant scores at 1, 6 and 12 weeks. RESULTS: Statistically significant improvements occurred in both groups. At 12 weeks, the SPADI and Con-stant score for SSNB improved to 9.62±10.07 and 36.95±3.43 respectively (p<0.001); and for IACI improved to 11.65±5.56 and 35.07±3.32 respectively (p <0.001). The difference in the scores between the 2 groups at 1st and 6th week was insignificant, but was statistically significant in favour of SSNB at 12 weeks (p=0.002). CONCLUSIONS: 1. Thus, from the present study it can be concluded that both Suprascapular Nerve Block and Intra-articular Corticosteroid injection are effective mo-dalities of treatment for Adhesive Capsulitis of the shoulder. 2. Suprascapular Nerve Block increased patients' pain tolerability for effective mobilization, the effect be-ing persistent even at 12 weeks following injection. 3. It was safer than Intra-articular Corticosteroid in-jection with less incidence of adverse effects in our study and the literature. 4. It is an easy-to-perform outpatient procedure, with minimal chance of infection and other complications. 5. In light of the above, we may recommend Su-prascapular Nerve Block as the initial procedure of choice in patients with Adhesive Capsulitis of Shoulder.

Current advances in regulation of bone homeostasis.

Bone homeostasis is securely controlled by the dynamic well-balanced actions among osteoclasts, osteoblasts and osteocytes. Osteoclasts are large multinucleated cells that degrade bone matrix and involve in the bone remodelling in conjunction with other bone cells, osteoblasts and osteocytes, the completely matured form of osteoblasts. Disruption of this controlling balance among these cells or any disparity in bone remodelling caused by a higher rate of resorption by osteoclasts over construction of bone by osteoblasts results in a reduction of bone matrix including bone mineral density (BMD) and bone marrow cells (BMCs). The dominating effect of osteoclasts results in advanced risk of bone crack and joint destruction in several diseases including osteoporosis and rheumatoid arthritis (RA). However, the boosted osteoblastic activity produces osteosclerotic phenotype and weakened its action primes to osteomalacia or rickets. On the other hand, senescent osteocytes predominately progress the senescence associated secretory phenotype (SASP) and may contribute to age related bone loss. Here, we discuss an advanced level work on newly identified cellular mechanisms controlling the remodelling of bone and crosstalk among bone cells as these relate to the therapeutic targeting of the skeleton.

Facts and Myths: Efficacies of Repurposing Chloroquine and Hydroxychloroquine for the Treatment of COVID-19.

The emergence of coronavirus disease 2019 (COVID-19) is caused by the 2019 novel coronavirus (2019-nCoV). The 2019-nCoV first broke out in Wuhan and subsequently spread worldwide owing to its extreme transmission efficiency. The fact that the COVID-19 cases and mortalities are reported globally and the WHO has declared this outbreak as the pandemic, the international health authorities have focused on rapid diagnosis and isolation of patients as well as search for therapies able to counter the disease severity. Due to the lack of known specific, effective and proven therapies as well as the situation of public-health emergency, drug repurposing appears to be the best armour to find a therapeutic solution against 2019-nCoV infection. Repurposing anti-malarial drugs and chloroquine (CQ)/ hydroxychloroquine (HCQ) have shown efficacy to inhibit most coronaviruses, including SARS-CoV-1 coronavirus. These CQ analogues have shown potential efficacy to inhibit 2019-nCoV in vitro that leads to focus several future clinical trials. This review discusses the possible effective roles and mechanisms of CQ analogues for interfering with the 2019-nCoV replication cycle and infection.

Mating Attributes Relating to Parasitization and Productivity in Habrobracon hebetor (Hymenoptera: Braconidae) Rearing on Host Indian Meal Moth (Lepidoptera: Pyralidae).

The mating attributes in relating to parasitism and progeny production capacity of the parasitoid Habrobracon hebetor Say, using Plodia interpunctella (Hübner) as a host, were investigated in laboratory studies. The results indicated that 100% of the host larvae were parasitized by different individuals of H. hebetor females that were mated by the same male. Mating duration did not differ significantly among different successive matings with different females and had no effect on the rate of parasitism. In general, pairs that had their copulation early after emergence exhibited the maximum rate of parasitism as compared to delayed intervals. Moreover, the age of the H. hebetor females had no effect on the percentage of parasitism. The maximum parasitism percentage was recorded for the H. hebetor individuals that had been developed from the age group of the 6-d-old adults. The male: female ratios did not differ significantly among the female age groups. The percentage of parasitism clearly indicated a decrease with the increase of the male: female ratio. Overall, the results of the present work can be further utilized in mass rearing and release of H. hebetor in biological control programs in stored product protection.

Comparison of 3 Days Amoxicillin Versus 5 Days Co-Trimoxazole for Treatment of Fast-breathing Pneumonia by Community Health Workers in Children Aged 2-59 Months in Pakistan: A Cluster-randomized Trial.

BACKGROUND: Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level. METHODS: We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2-59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol. RESULTS: Out of the 15 749 cases enrolled in the study, 9153 cases in intervention and 6509 cases in control clusters were included in the analysis. Treatment failure rates were 3.6% (326) in intervention clusters and 9.1% (592) in control clusters. After adjusting for clustering, the risk of treatment failure was lower in intervention clusters (risk difference [RD] -5.5%, 95% confidence interval [CI] -7.4--3.7%) than in control clusters. Children with incomplete adherence had a small increase in treatment failure versus those with complete adherence (RD 2.9%, 95% CI 1.6-4.1%). No deaths or serious adverse events occurred. CONCLUSIONS: A 3-day course of oral amoxicillin, administered by LHWs, is an effective and safe treatment for fast-breathing pneumonia in children 2-59 months of age. A shorter course of amoxicillin improves adherence to therapy, is low in cost, and puts less pressure on antimicrobial resistance. CLINICAL TRIALS REGISTRATION: ISRCTN10618300.

Long-term monitoring of radioactivity in fish from New York waters.

As part of an environmental surveillance program operated by the New York State (NYS) Department of Health, measurements of various radionuclides in aquatic life (primarily fish) collected from waterways in NYS have occurred for decades. An investigation was undertaken to gain a better understanding of the occurrence, activity levels, and extent of radionuclide variations in aquatic life obtained from local waterways in relation to concentrations reported in fish from sites outside NYS (e.g., Pacific Ocean tuna). The man-made isotopes (137)Cs and (90)Sr were detectable at activities below 1 Bq/kg in the edible portions of fish from most NYS waterways, with the exception of greater activities in fish collected downstream of Brookhaven National Laboratory. Calculated effective doses resulting from eating the fish, estimated as 11-390 nSv/yr for (137)Cs and 0.3-7.9 nSv/yr for (90)Sr, are considered extremely low.

Effect of community mobilization on appropriate care seeking for pneumonia in Haripur, Pakistan.

BACKGROUND: Appropriate and timely care seeking reduces mortality for childhood illnesses including pneumonia. Despite over 90 000 Lady Health Workers (LHWs) deployed in Pakistan, whose tasks included management of pneumonia, only 16% of care takers sought care from them for respiratory infections. As part of a community case management trial for childhood pneumonia, community mobilization interventions were implemented to improve care seeking from LHWs in Haripur district, Pakistan. The objective of the study was to increase the number of children receiving treatment for pneumonia and severe pneumonia by Lady Health Workers (LHWs) through community mobilization approaches for prompt recognition and care seeking in 2 to 59 month-old children. METHODS: To assess pneumonia care seeking practices, pre and post-intervention household surveys were conducted in 28 target Union Councils. Formative research to improve existing LHW training materials, job aids and other materials was carried out. Advocacy events were organized, LHWs and male health promoters were trained in community mobilization, non-functional women and male health committees were revitalized and LHWs and male health promoters conducted community awareness sessions. RESULTS: The community mobilization interventions were implemented from April 2008 - December 2009. Project and LHW program staff organized 113 sensitization meetings for opinion leaders, which were attended by 2262 males and 3288 females. The 511 trained LHWs organized 6132 community awareness sessions attended by 50 056 women and 511 male promoters conducted 523 sessions attended by 7845 males. In one year period, the number of LHWs treating pneumonia increased from 11 in April 2008 to 505 in March 2009. The care seeking from LHWs for suspected pneumonia increased from 0.7% in pre-intervention survey to 49.2% in post-intervention survey. CONCLUSION: The increase in care seeking from LHWs benefited the community through bringing inexpensive appropriate care closer to home and reducing burden on overstretched health facilities. The community mobilization interventions led to improvements in appropriate care seeking that would not have been achievable just by strengthening pneumonia case management skills of LHWs. In addition to strengthening skills, community mobilization and behavior change activities should also be included in community case management programmes.

Improved anti-diabetic activity of glibenclamide using oral self nano emulsifying powder.

The objective of the present study was to improve solubility, dissolution rate and therapeutic efficacy of a BCS Class II drug, glibenclamide by using oral self nano emulsifying powder. The powder was prepared by adsorbing the mixture of oil, surfactant and co-surfactant onto a carrier with large surface area; Aerosil 200. The ratios of oil and Smix (surfactant/co-surfactant mixture) required to produce an emulsion was optimized based on percentage transmittance studies and particle size determinations. The optimized formulation was subjected to in vitro dissolution study and in vivo therapeutic efficacy in rabbits by monitoring blood glucose levels. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction studies revealed that the drug was present in amorphous form in the final formulation. The in vivo study in rabbits indicated the improved therapeutic efficacy of glibenclamide in self-nanoemulsifying powder compared to plain drug.

Low rates of treatment failure in children aged 2-59 months treated for severe pneumonia: a multisite pooled analysis.

BACKGROUND: Despite advances in childhood pneumonia management, it remains a major killer of children worldwide. We sought to estimate global treatment failure rates in children aged 2-59 months with World Health Organization-defined severe pneumonia. METHODS: We pooled data from 4 severe pneumonia studies conducted during 1999-2009 using similar methodologies. We defined treatment failure by day 6 as death, danger signs (inability to drink, convulsions, abnormally sleepy), fever (≥38°C) and lower chest indrawing (LCI; days 2-3), LCI (day 6), or antibiotic change. RESULTS: Among 6398 cases of severe pneumonia from 10 countries, 564 (cluster adjusted: 8.5%; 95% confidence interval [CI], 5.9%-11.5%) failed treatment by day 6. The most common reasons for clinical failure were persistence of fever and LCI or LCI or fever alone (75% of failures). Seventeen (0.3%) children died. Danger signs were uncommon (<1%). Infants 6-11 months and 2-5 months were 2- and 3.5-fold more likely, respectively, to fail treatment (adjusted OR [AOR], 1.8 [95% CI, 1.4-2.3] and AOR, 3.5 [95% CI, 2.8-4.3]) as children aged 12-59 months. Failure was increased 7-fold (AOR, 7.2 [95% CI, 5.0-10.5]) when comparing infants 2-5 months with very fast breathing to children 12-59 months with normal breathing. CONCLUSIONS: Our findings demonstrate that severe pneumonia case management with antibiotics at health facilities or in the community is associated with few serious morbidities or deaths across diverse geographic settings and support moves to shift management of severe pneumonia with oral antibiotics to outpatients in the community.

Household costs for treatment of severe pneumonia in Pakistan.

Current World Health Organization (WHO) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral. However, high treatment cost is a major barrier for communities. We compared household costs for referred cases with management by lady health workers (LHWs) using oral antibiotics. This study was nested within a cluster randomized trial in Haripur, Pakistan. Data on direct and indirect costs were collected through interviews and record reviews in the 14 intervention and 14 control clusters. The average household cost/case for a LHW managed case was $1.46 compared with $7.60 for referred cases. When the cost of antibiotics provided by the LHW program was excluded from the estimates, the cost/case came to $0.25 and $7.51 for the community managed and referred cases, respectively, a 30-fold difference. Expanding severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population, preventing many child deaths.

Community case management of severe pneumonia with oral amoxicillin in children aged 2-59 months in Haripur district, Pakistan: a cluster randomised trial.

BACKGROUND: First dose oral co-trimoxazole and referral are recommended for WHO-defined severe pneumonia. Difficulties with referral compliance are reported in many low-resource settings, resulting in low access to appropriate treatment. The objective in this study was to assess whether community case management by lady health workers (LHWs) with oral amoxicillin in children with severe pneumonia was equivalent to current standard of care. METHODS: In Haripur district, Pakistan, 28 clusters were randomly assigned with stratification in a 1:1 ratio to intervention and control clusters by use of a computer-generated randomisation sequence. Children were included in the study if they were aged 2-59 months with WHO-defined severe pneumonia and living in the study area. In the intervention clusters, community-based LHWs provided mothers with oral amoxicillin (80-90 mg/kg per day or 375 mg twice a day for infants aged 2-11 months and 625 mg twice a day for those aged 12-59 months) with specific guidance on its use. In control clusters, LHWs gave the first dose of oral co-trimoxazole (age 2-11 months, sulfamethoxazole 200 mg plus trimethoprim 40 mg; age 12 months to 5 years, sulfamethoxazole 300 mg plus trimethoprim 60 mg) and referred the children to a health facility for standard of care. Participants, carers, and assessors were not masked to treatment assignment. The primary outcome was treatment failure by day 6. Analysis was per protocol with adjustment for clustering within groups by use of generalised estimating equations. This study is registered, number ISRCTN10618300. FINDINGS: We assigned 1995 children to treatment in 14 intervention clusters and 1477 in 14 control clusters, and we analysed 1857 and 1354 children, respectively. Cluster-adjusted treatment failure rates by day 6 were significantly reduced in the intervention clusters (165 [9%] vs 241 [18%], risk difference -8·9%, 95% CI -12·4 to -5·4). Further adjustment for baseline covariates made little difference (-7·3%, -10·1 to -4·5). Two deaths were reported in the control clusters and one in the intervention cluster. Most of the risk reduction was in the occurrence of fever and lower chest indrawing on day 3 (-6·7%, -10·0 to -3·3). Adverse events were diarrhoea (n=4) and skin rash (n=1) in the intervention clusters and diarrhoea (n=3) in the control clusters. INTERPRETATION: Community case management could result in a standardised treatment for children with severe pneumonia, reduce delay in treatment initiation, and reduce the costs for families and health-care systems. FUNDING: United States Agency for International Development (USAID).

Paying health workers for performance in Battagram district, Pakistan.

BACKGROUND: There is a growing interest in using pay-for-performance mechanisms in low and middle-income countries in order to improve the performance of health care providers. However, at present there is a dearth of independent evaluations of such approaches which can guide understanding of their potential and risks in differing contexts. This article presents the results of an evaluation of a project managed by an international non-governmental organisation in one district of Pakistan. It aims to contribute to learning about the design and implementation of pay-for-performance systems and their impact on health worker motivation. METHODS: Quantitative analysis was conducted of health management information system (HMIS) data, financial records, and project documents covering the period 2007-2010. Key informant interviews were carried out with stakeholders at all levels. At facility level, in-depth interviews were held, as were focus group discussions with staff and community members. RESULTS: The wider project in Battagram had contributed to rebuilding district health services at a cost of less than US$4.5 per capita and achieved growth in outputs. Staff, managers and clients were appreciative of the gains in availability and quality of services. However, the role that the performance-based incentive (PBI) component played was less clear--PBI formed a relatively small component of pay, and did not increase in line with outputs. There was little evidence from interviews and data that the conditional element of the PBIs influenced behaviour. They were appreciated as a top-up to pay, but remained low in relative terms, and only slightly and indirectly related to individual performance. Moreover, they were implemented independently of the wider health system and presented a clear challenge for longer term integration and sustainability. CONCLUSIONS: Challenges for performance-based pay approaches include the balance of rewarding individual versus team efforts; reflecting process and outcome indicators; judging the right level of incentives; allowing for very different starting points and situations; designing a system which is simple enough for participants to comprehend; and the tension between independent monitoring and integration in a national system. Further documentation of process and cost-effectiveness, and careful examination of the wider impacts of paying for performance, are still needed.

Antibiotic susceptibility profile of Aeromonas spp. isolates from food in Abu Dhabi, United Arab Emirates.

A total of 57 Aeromonas isolates from food samples such as fresh and frozen chicken, game birds, pasteurized milk, baby food, bakery products, fruit and vegetables, fish, and water from Abu Dahbi, UAE were investigated for antibiotic susceptibility profile. Most strains were resistant to penicillins (ticarcillin, mezlocillin, oxacillin, piperacillin), sulfamethoxazole, trimethoprim and macrolides (erythromycin, vancomycin, clindamycin) but sensitive to tetracycline, chloramphenicol, nitrofurantoin, aminoglycosides (amikacin, gentamicin, tobramycin), cephalosporins (cefuroxime, ceftrioxone, cefazolin, cephalexin, cephalothin, cefoxitin, cefotaxime), quinolone (ciprofloxacin), colistin sulphate and SXT (trimethoprim-sulfamethoxazole). On the other hand, many antibiotics showed excellent inhibitory activity (>75% strains were sensitive to them) against all the strains tested. These include cefuroxime, ceftrioxone, ciprofloxacin, colistin, amikacin, gentamicin, tetracycline, chloramphenicol, nitrofurantoin, cefotaxime and tobramycin. In conclusion, the results show a detailed pattern of sensitivity of the various Aeromonas spp. isolates to a variety of antibiotics and provide useful information in the context of selective isolation and phenotypic identification of the aeromonads from food.