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Background: Measuring the quality of hospital admission care is essential to ensure that standards of practice are met and continuously improved to reduce morbidity and mortality associated with the illnesses most responsible for inpatient deaths. The Paediatric Admission Quality of Care (PAQC) score is a tool for measuring adherence to guidelines for children admitted with acute illnesses in a low-income setting. We aimed to explore the external and criterion-related validity of the PAQC score by investigating its association with mortality using data drawn from a diverse sample of Kenyan hospitals. Methods: We identified children admitted to Kenyan hospitals for treatment of malaria, pneumonia, diarrhoea, or dehydration from datasets from three sources: an observational study, a clinical trial, and a national cross-sectional survey. We extracted variables describing the process of care provided to patients at admission and their eventual outcomes from these data. We applied the PAQC scoring algorithm to the data to obtain a quality-of-care score for each child. We assessed external validity of the PAQC score by its systematic replication in datasets that had not been previously used to investigate properties of the PAQC score. We assessed criterion-related validity by using hierarchical logistic regression to estimate the association between PAQC score and the outcome of mortality, adjusting for other factors thought to be predictive of the outcome or responsible for heterogeneity in quality of care. Findings: We found 19 065 eligible admissions in the three validation datasets that covered 27 hospitals, of which 12 969 (68%) were complete cases. Greater guideline adherence, corresponding to higher PAQC scores, was associated with a reduction in odds of death across the three datasets, ranging between 9% (odds ratio 0·91, 95% CI 0·84–0·99; p=0·031) and 30% (0·70, 0·63–0·78; p Interpretation: The PAQC score, designed as an index of the technical quality of care for the three commonest causes of admission in children, is also associated with mortality. This finding suggests that it could be a meaningful summary measure of the quality of care for common inpatient conditions and supports a link between process quality and outcome. It might have potential for application in low-income countries with similar disease profiles and in which paediatric practice recommendations are based on WHO guidelines.

Summary Background & aims Understanding mature breastmilk immunology may benefit infants chronically exposed to infectious pathogens in resource-limited regions. Methods This prospective rural/semi-rural Tanzanian cohort of women (n = 102 at delivery; 38% HIV-positive) and their infants (n = 102) investigated breastmilk, maternal and infant serum immunoglobulins (IgA/IgG 1–4 /IgM) and cytokines (IL-1β/IL-2/IL-6/IL-10/IL-12p70/IL-13/IL-15/TNF-α/IFN-γ) at 1, 2, 3, 6-months postpartum. Results Milk immunoglobulins followed an inverse U-shaped pattern, while cytokine patterns were mixed. Exclusive breastfeeding duration and feeding intensity were associated with greater breastmilk total immunoglobulin and IgA, IgG 1-3 and IL-12p70 concentrations. Maternal mastitis, fever or cough was associated with higher breastmilk total cytokine concentrations, while infant fever was associated with lower milk immunoglobulins or cytokines. Strong (r ≥ 0.40) to weak (r = 0.20–0.29) positive correlations between maternal serum-breastmilk or breastmilk-infant serum immunoglobulins were evident. Breastmilk cytokines were moderate to weakly negatively correlated with infant serum. Breastmilk immunology did not differ by maternal malnutrition or HIV-seropositivity. Conclusions Mature breastmilk is a dynamic source of many specific and non-specific immune factors associated with maternal and infant health and infant nutrition. Breastfeeding practices are associated with differential breastmilk immunological composition providing immunological support for universal recommendations to exclusively breastfeed for 6-months.

To evaluate whether the implementation of a multiplex gastrointestinal pathogen panel (GIP) was associated with changes in Clostridioides difficile (C difficile) testing and detection rates.We conducted an observational study using interrupted time series analysis and included pediatric patients with testing capable of detecting C difficile. From 2013 to 2015 ("conventional diagnostic era"), stool testing included C difficile-selective polymerase chain reaction and other pathogen-specific tests. From 2015 to 2017 ("GIP era"), C difficile polymerase chain reaction was available along with the GIP, which detected 22 pathogens including C difficile, and replaced the need for additional tests. Outcomes included C difficile testing and detection rates in ambulatory, emergency department, and inpatient settings.There were 6841 tests performed and 1214 C difficile positive results. Across the 3 settings, GIP era had significantly higher C difficile testing (1.7-2.3 times higher) and C difficile detection rates (1.9-3.4 times higher) compared with conventional diagnostic era. After adjusting for the number of tests performed, detection rates were no longer significantly different. Of C difficile positive GIPs, 31% were coinfected with another organism. With GIP testing, patients 1 year of age had a significantly higher C difficile percent positivity than 2-year-old (P = .02) and 3- to 18-year-old children (P .01). Younger children with C difficile were more likely to be coinfected (P .01).Introducing a multiplex panel led to increased C difficile testing, which resulted in increased C difficile detection rates and potential identification and treatment of colonized patients. This highlights an important target for diagnostic stewardship and the challenges associated with multiplex testing.

BACKGROUND: Fisherfolks (FF) and female sex workers (FSW) in Uganda could be suitable key populations for HIV vaccine efficacy trials because of the high HIV incidence and good retention in observational cohorts. However, the observed HIV incidence may differ in participants who enroll into a trial. We used simulated vaccine efficacy trials (SiVET) nested within observational cohorts in these populations to evaluate this difference. METHODS: SiVETs were nested in two observational cohorts (Jul 2012-Apr 2014 in FF and Aug 2014-Apr 2017 in FSW). From Jan 2012 all observational cohort participants (aged 18-49 years) presenting for quarterly visits were screened for enrolment into SiVETs, until 572 were enrolled. Those not enrolled (screened-out or not screened) in SiVET continued participation in the observational cohorts. In addition to procedures in the observational cohorts (HIV testing & risk assessment), SiVET participants were given a licensed Hepatitis B vaccine mimicking a schedule of a possible HIV vaccine, and followed-up for 12 months. FINDINGS: In total, 3989 participants were enrolled into observational cohorts (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). Of these 3622 (90.8%) returned at least once, 672 (44.1%) were screened and 572 enrolled in the SiVETs. HIV incidence pre SIVETs was 4.5/100 person years-at-risk (pyar), 95%CI (3.8-5.5). HIV incidence in SiVET was 3.5/100 pyar, (2.2-5.6) and higher in those not enrolled in the SiVET, 5.9/100 pyar, (4.3-8.1). This difference was greatest among FF. In the 12 months post-SIVET period (FF, May 2014-Apr 2015 and FSW, May 2017-Apr 2018), the HIV incidence was 3.7/100 pyar, (2.5-5.8). INTERPRETATION: HIV incidence was lower in SiVET participants compared to non-SiVET. This difference was different for the two populations. Researchers designing HIV efficacy trials using observational cohort data need to consider the potential for lower than expected HIV incidence following screening and enrolment.

Background Effective interventions to reduce the incidence of HIV, other sexually transmitted infections (STIs) and unwanted pregnancy among adolescents in sub-Saharan Africa are urgently needed. This paper describes the rationale and design of a randomised trial of the impact of an innovative sexual health intervention among adolescents in rural Mwanza Region, Tanzania. Methods The MEMA kwa Vijana intervention comprises a teacher-led, peer-assisted sexual health education programme for students in the last 3 years of primary school, training and supervision of health workers in the provision of youth-friendly health services, peer condom promotion and distribution, and wider community activities. Detailed process evaluation was conducted and the impact of the intervention was evaluated through a community-randomised trial in which a cohort of 9645 adolescents was followed up for 3 years. Both process and impact evaluation used multiple assessment methods. Impact measures included incidence and prevalence of HIV and other STIs, pregnancy rates, knowledge and reported attitudes and sexual behaviour, as well as qualitative assessments. Results Results of the baseline survey of the cohort have been presented previously. The outcome of the trial will be reported separately. Conclusions Behaviour change interventions among adolescents have been widely advocated, but there have been few rigorously designed trials of their effectiveness, particularly in developing countries, and measurement of sexual behaviour is particularly problematic in this age group. The MEMA kwa Vijana trial was undertaken to address these problems and to collect rigorous evidence on the effectiveness of an innovative intervention, designed to be implemented on a very large scale.

The HIV epidemic in sub-Saharan Africa has been characterised by the predominance of heterosexual transmission. Patterns of sexual behaviour have been implicated in the spread of the epidemic, but few quantitative data are available on sexual behaviour in rural populations in Africa. This paper reports data from a survey of 1117 adults aged 15–54 years selected randomly from twelve rural communities in Mwanza Region, Tanzania. Sexual debut occurred early, 50% of women and 46% of men reporting first sex before age 16. On average, women married 1.8 years and men 6.1 years after their sexual debut. In women, age at sexual debut appears to have increased over time, in parallel with an increase in age at first marriage. Men were generally married later, to women around five to ten years younger than themselves. Marital dissolution and remarriage were common in both sexes. Reported numbers of sexual partners were compared with those recorded in a population survey in Britain. More men reported 10 or more lifetime partners, or three or more partners in the past year, in rural Mwanza (48% and 29%) than in Britain (24% and 6%). Women reported fewer partners, and results were broadly similar to British data. Casual sex during the past year was reported by 53% of the men and 15% of the women, but only 2% of men reported sexual contact with bar girls or commercial sex workers. Only 20% of men and 3% of women had ever used a condom. Interventions are needed to reduce the high levels of sexual partner change and casual sex, and low levels of condom use, recorded in this rural population. Targeting of interventions to traditional “core groups” may be of limited value in rural areas, and additional strategies are needed, focusing particularly on teenagers who are at high risk of HIV and other sexually transmitted diseases.

Phospholipase C (lecithinase or phosphatidylcholine Phosphorylase) catalyzes the hydrolysis of lecithin into phosphorylcholine and 1,2-diglyceride. Bacterial production of phospholipase C may damage reproductive tract tissues by both direct and indirect mechanisms. Use of the synthetic substrate p-nitrophenylphosphorylcholine polspholipase C activity was determined in 204 isolates representative of those found in female genital tract. Multiple aerobic (28%) and anaerobic (28%) reproductive tract microorganisms showed phospholipase C activity. Phospholipase C-producing isolates included strains of Bacteroides fragilis, B. bivius, B. thetaiotaomicron, Gardnerella vaginalis , and group B streptococcus. Phospholipase C activity was heterogenous; not all isolates that belong to a particular species showed activity. Phospholipase C production may be a possible virulence factor produced by a number of microflora commonly implicated in various reproductive tract infections or conditions, as well as in some instances of preterm birth.

In a prospective study of 202 women (gestational age 24 +/- 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (greater than or equal to 10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth.

The rapid expansion of antiretroviral treatment for HIV-infected adults which has been helped by WHOs "3 by 5" strategy the Global Fund to fight AIDS Tuberculosis and Malaria the Presidents Emergency Plan for AIDS Relief and other international initiatives demands a scale-up of voluntary HIV counselling and testing services in participating countries. In Tanzania for example the expansion aimed to have more than 600 voluntary HIV counselling and testing sites by the end of 2006 representing an increase of almost 250% since 2005. Data-collection activities in voluntary HIV counselling and testing clinics are increasingly expected to fulfill donor-driven reporting requirements that include programme monitoring and assessment. Increases in clinic coverage and recorded indicators and the desire to measure the effect of HIV-related interventions on the evolution of the epidemic have led to suggestions to use data from these clinics for HIV and behavioural surveillance. We believe that such use of this data is not appropriate: the data are inherently biased and the function of the clinics could be compromised. (excerpt)

Clostridium sordellii is a common soil and enteric bacterium that is infrequently recovered from the vagina. We describe three women in which C. sordellii caused puerperal infection and a distinctive and lethal toxic shock-like syndrome. Patients were less than 1 week post partum and each had a single, limited focus of infection including infection associated with a retained vaginal sponge, a cesarean section operative site, and endometritis. Each patient had a distinctive course characterized by sudden onset of clinical shock marked by severe and unrelenting hypotension associated with marked, generalized tissue edema and "third spacing" with increased hematocrit, presence of marked leukemoid reaction with total neutrophil counts of 84,000/mm3, 66,000/mm3, and 93,600/mm3, absence of rash or fever, limited or no myonecrosis, and a rapid and uniformly lethal course. Hypoalbuminemia was also noted. Similar findings were noted in prior isolated reports of C. sordellii-mediated postpartum or surgical infection. Treatment of animals with C. sordellii or closely related C. difficile toxins produces similar findings. We suggest that localized infection with toxin-producing strains of C. sordellii can produce a rapidly lethal toxic shock-like syndrome. Further study and earlier recognition of this syndrome may be life-saving in other patients.

Six soft tissue infections (three epiglottitis, one cellulitis, one pneumonia, and one arthritis) with ampicillin-resistant Haemophilus influenzae were treated initially with high doses of ampicillin (200 to 400 mg/kg/day intravenously) alone and had good clinical responses. All had documented bacteremia with H. influenzae. One child was treated only with ampicillin; treatment in the remainder was changed to oral therapy with other antibiotics to facilitate discharge. There was no recurrence of disease. Disc diffusion studies done on clinical isolates of both resistant and sensitive organisms indicate a break point at which the resistant organism shows progressive sensitivity to increasingly higher concentrations of ampicillin.

Sore throat can be caused by different microorganisms and diseases. Most cases of acute pharyngitis are caused by group A streptococcus or viruses; however, uncommon organisms may be suggested by other clinical information or the persistence of symptoms. A thorough history and physical examination are essential for the appropriate selection of diagnostic tests for sore throat. Routine testing for the uncomplicated case should consist of a pharyngeal culture in most patients, with rapid streptococcal antigen testing only for the more severe cases. Those with positive streptococcal tests should be treated to prevent rheumatic fever and mitigate symptoms in severe cases. Sore throat caused by viruses usually resolves spontaneously. Cases that persist should be thoroughly re-evaluated, with alternative causes being considered. Acute epiglottitis is a medical emergency and requires treatment with appropriate antibiotics for Hemophilus influenzae type b and intubation.

An unusual cluster of Reye syndrome was associated with an outbreak of influenza A (H1N1) infections in the state of Colorado. Two of the 16 affected children had had prior episodes of Reye syndrome following respiratory infections, and one had had transverse myelitis following varicella. A serologic study of patients treated at a children's hospital and serum specimens submitted to the state health department revealed that approximately 59% of children in Colorado had been infected with the H1N1 strain of influenza A over a two-year period. Based upon this serologic survey, the minimum and maximum rates of Reye syndrome associated with H1N1 infections were calculated to be 2.5 and 4.3 cases per 100,000 H1N1 infections, respectively. A retrospective analysis of admissions to four referral hospitals in Denver failed to reveal any unusual clustering of Reye syndrome with outbreaks of influenza A H3N2 infections during 1975-1978. The reason for an association between Reye syndrome and the H1N1 strain but not the H3N2 strains of influenza A remains unclear.

The suspected diagnosis of H. influenzae type b cellulitis is usually based on the typically described violaceous coloration of the affected area, found in approximately 45% of the cases, and by the localization of the lesions over the face or periorbital area, reported in approximately two-thirds of the patients. 2 The final diagnosis, sometimes unsuspected, is most frequently made from the results of blood cultures, which are positive in approximately 80% of the cases? Recently Goetz and TafarP reported the value of needle aspiration of the cellulitis as a means of increasing the number of patients in whom a definitive etiologic diagnosis can be made; two of their three patients had positive cultures from aspirate material. Our experience is similar. It is noteworthy that one of our patients had a positive aspirate culture in the presence of a negative blood culture, emphasizing the importance of obtaining samples from both sites. Furthermore, as seen in our small series, it becomes particularly important to obtain a Gram stain of the aspirate. A preliminary diagnosis can often be made and appropriate antibiotic treatment initiated without delay. The predominance of males in our series is of interest. A recent review of H. influenzae type b cellulitis failed to disclose a sex predilection. ~

controlled maternal metabolic status cannot be ruled out as important contributing factors to postnatal hyperbilirubinemia. No correlation was found between VECO and serum bilirubin concentration at the time of the determination or at its peak, but the total bilirubin produced, though obligatorily reflected in VECO, may not be directly reflected in the serum bilirubin concentration. The latter would also depend on hepatic uptake, conjugation, excretion, and enterohepatic circulation of bilirubin, suggesting that one or more of these other factors may also play a role in the hyperbilirubinemia seen in IDMs. The weight ratio as an index of macrosomia has been felt to be an indicator of diabetes control of the mother, and has been shown to be significantly correlated with the presence of HgbAlc in the mother. TM Accepting this criterion of maternal diabetes control, it would seem that increased excretion of CO is directly related to poor maternal diabetes control. This implies that prenatal metabolic influences exerted on the fetus by the mother may affect postnatal bilirubin production in the infant. That this effect is most evident in macrosomic infants would be expected, since these infants are the ones presumably most adversely affected by their prenatal environment. Since the mean "VECO for IDMs who were not macrosomic was also increased, other compounding factors which are not necessarily associated with macrosomia, such as varying degrees of postnatal caloric deprivation, may be contributing to the increased production in these infants. 1

IN 1 836, V o N L U D W I G described five cases of "gangrenous induration of the connective tissues of the neck. ''1 Since this initial report, Ludwig angina has remained an unusual entity but one with great clinical significance. Antibiotic usage has reduced its occurrence, but the associated respiratory obstruction makes it imperat ive that the practicing pediatrician be familiar with its presentation. Four children with Ludwig angina have recently been treated, and these cases are reported to underl ine the clinical presentation.