Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study.

The mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1-14 years (-7.7%, 95% PI -20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group.

Imaging in gynecological disease (25): clinical and ultrasound characteristics of intramural pregnancy.

OBJECTIVE: To describe the clinical and sonographic characteristics of intramural pregnancy, as well as the available management options and treatment outcomes. METHODS: This was a retrospective single-center study of consecutive patients with a sonographic diagnosis of intramural pregnancy between November 2008 and November 2022. An intramural pregnancy was diagnosed on ultrasound when a pregnancy was implanted within the uterine corpus, above the level of the internal cervical os and separate from the interstitial section of the Fallopian tube, and extended beyond the decidual-myometrial junction. Clinical, ultrasound, relevant surgical and histological information and outcomes were retrieved from each patient's record and analyzed. RESULTS: Eighteen patients were diagnosed with an intramural pregnancy during the study period. Their median age was 35 (range, 28-43) years and the median gestational age at diagnosis was 8 + 1 (range, 5 + 5 to 12 + 0) weeks. Vaginal bleeding with or without abdominal pain was the most common presenting symptom, recorded in eight patients. Nine (50%) patients had a partial and nine (50%) had a complete intramural pregnancy. Embryonic cardiac activity was present in eight (44%) pregnancies. The majority of pregnancies (n = 10 (56%)) were initially managed conservatively, including expectant management in eight (44%) cases, local injection of methotrexate in one (6%) and embryocide in one (6%). Conservative management was successful in nine of the 10 (90%) pregnancies, with a median time to serum human chorionic gonadotropin resolution of 71 (range, 35-143) days. One patient with an ongoing live pregnancy had an emergency hysterectomy for a major vaginal bleed at 20 weeks' gestation. No other patient managed conservatively experienced any significant complication. The remaining eight (44%) patients had primary surgical treatment, comprising transcervical suction curettage in seven (88%) of these cases, while one patient presented with uterine rupture and underwent emergency laparoscopy and repair. CONCLUSIONS: We describe the ultrasound features of partial and complete intramural pregnancy, demonstrating key diagnostic features. Our series suggests that, when intramural pregnancy is diagnosed before 12 weeks' gestation, it can be managed either conservatively or by surgery, with preservation of reproductive function in most women. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

In praise of Prais-Winsten: An evaluation of methods used to account for autocorrelation in interrupted time series.

Interrupted time series are increasingly being used to assess the population impact of public health interventions. These data are usually correlated over time (auto correlated) and this must be accounted for in the analysis. Typically, this is done using either the Prais-Winsten method, the Newey-West method, or autoregressive-moving-average (ARMA) modeling. In this paper, we illustrate these methods via a study of pneumococcal vaccine introduction and explore their performance under 20 simulated autocorrelation scenarios with sample sizes ranging between 20 and 300. We show that in terms of mean square error, the Prais-Winsten and ARMA methods perform best, while in terms of coverage the Prais-Winsten method generally performs better than other methods. All three methods are unbiased. As well as having good statistical properties, the Prais-Winsten method is attractive because it is decision-free and produces a single measure of autocorrelation that can be compared between studies and used to guide sample size calculations. We would therefore encourage analysts to consider using this simple method to analyze interrupted time series.

Psychological impact of simple scoring system for predicting early pregnancy outcome in pregnancy of uncertain viability: randomized controlled trial.

OBJECTIVE: To investigate whether psychological wellbeing of women with an intrauterine pregnancy of uncertain viability can be modified during the waiting period to final diagnosis, by offering predictive information regarding the likely outcome of the pregnancy (chance of ongoing viability). METHODS: This was a single-center two-arm randomized controlled trial conducted over 18 months at a teaching hospital in London, UK. Consecutive eligible women attending the early pregnancy assessment unit with an interim ultrasound finding of intrauterine pregnancy of uncertain viability were recruited. All women were offered a follow-up ultrasound scan after 14 days. Participants were randomized to receive a prediction score for ongoing viability at 14 days or routine care (control). Anxiety, depression and worry symptoms were assessed using validated self-report questionnaires (hospital anxiety and depression scale (HADS), Penn state worry questionnaire (PSWQ)) prior to randomization and at two further timepoints during the waiting period preceding final diagnosis. The change in psychological scores over the study period was analyzed. The secondary outcome was the perceived value of the risk prediction tool reported by participants. RESULTS: A total of 278 women participated in this study. After adjusting for baseline scores, no difference in anxiety, depression or worry scores was demonstrated between control and intervention groups at either timepoint. Subgroup analysis, first of women with high initial anxiety (HADS > 11) or worry (PSWQ ≥ 45), and second of women with a more favorable predicted prognosis (≥ 75% chance of ongoing viability), demonstrated no difference between intervention and control groups. Despite this, 76/110 (69.1% (95% CI, 60.5-78.4%)) women who provided feedback in the intervention group found it to be helpful and 97/110 (88.2% (95% CI, 81.0-93.7%)) reported that they would use the tool again. CONCLUSION: Current prediction tools may be useful for healthcare professionals to guide management and optimize utilization of early pregnancy resources. However, in this study, implementation of an accurate tool did not result in an objective measurable benefit to patients in terms of reduction in anxiety, depression and worry symptoms experienced during the waiting period to final outcome compared with women who did not receive a prediction score. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels.

As countries decide on vaccination strategies and how to ease movement restrictions, estimating the proportion of the population previously infected with SARS-CoV-2 is important for predicting the future burden of COVID-19. This proportion is usually estimated from serosurvey data in two steps: first the proportion above a threshold antibody level is calculated, then the crude estimate is adjusted using external estimates of sensitivity and specificity. A drawback of this approach is that the PCR-confirmed cases used to estimate the sensitivity of the threshold may not be representative of cases in the wider population-e.g., they may be more recently infected and more severely symptomatic. Mixture modelling offers an alternative approach that does not require external data from PCR-confirmed cases. Here we illustrate the bias in the standard threshold-based approach by comparing both approaches using data from several Kenyan serosurveys. We show that the mixture model analysis produces estimates of previous infection that are often substantially higher than the standard threshold analysis.

Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review.

BACKGROUND: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. METHODS: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. RESULTS: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. CONCLUSION: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose-response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

Intra- and interobserver reproducibility of pelvic ultrasound for the detection and measurement of endometriotic lesions.

STUDY QUESTION: What is the interobserver and intraobserver reproducibility of pelvic ultrasound for the detection of endometriotic lesions? SUMMARY ANSWER: Pelvic ultrasound is highly reproducible for the detection of pelvic endometriotic lesions. WHAT IS KNOWN ALREADY: Transvaginal ultrasound (TVS) has been widely adopted as the first-line assessment for the diagnosis and assessment of pelvic endometriosis. Severity of endometriosis as assessed by ultrasound has been shown to have good concordance with laparoscopy (kappa 0.79). The reproducibility of TVS for assessment of ovarian mobility and pouch of Douglas obliteration using the 'sliding sign' has already been described in the literature. However, there is no available data in the literature to demonstrate the intraobserver repeatability of measurements for endometriotic cysts and nodules. STUDY DESIGN SIZE DURATION: This was a prospective observational cross-sectional study conducted over a period of 12 months. We included 50 consecutive women who were all examined by two operators (A and B) during their clinic attendance. PARTICIPANTS/MATERIALS SETTING METHODS: The study was carried out in a specialist endometriosis centre. We included all consecutive women who had ultrasound scans performed independently by two experienced operators during the same visit to the clinic. The outcomes of interest were the inter- and intraobserver reproducibility for the detection of endometriotic lesions. We also assessed repeatability of the measurements of lesion size. MAIN RESULTS AND THE ROLE OF CHANCE: There was a good level of agreement between operator A and operator B in detecting the presence of pelvic endometriotic lesions (k = 0.72). There was a very good level of agreement between operators in identifying endometriotic cysts (k = 0.88) and a good level of agreement in identifying endometriotic nodules (k = 0.61). The inter- and intraobserver repeatability of measuring endometriotic cysts was excellent (intra-class correlation (ICC) ≥ 0.98). There was good interobserver measurement repeatability for bowel nodules (ICC 0.88), but the results for nodules in the posterior compartment were poor (ICC 0.41). The intraobserver repeatability for nodule size measurements was good for both operators (ICC ≥0.86). LIMITATIONS REASONS FOR CAUTION: Within this cohort, there was insufficient data to perform a separate analysis for nodule size in the anterior compartment. All examinations were performed within a specialised unit with a high prevalence of deep endometriosis. Our findings may not apply to operators without intensive ultrasound training in the diagnosis of pelvic endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: These findings are important because ultrasound has been widely accepted as the first-line investigation for the diagnosis of pelvic endometriosis, which often determines the need for future investigations and treatment. The detection and measurement of bowel nodules is essential for anticipation of surgical risk and planning surgical excision. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest. No funding was obtained for this work.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Triaging women with pregnancy of unknown location using two-step protocol including M6 model: clinical implementation study.

OBJECTIVE: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged. METHODS: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics. RESULTS: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines. CONCLUSIONS: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Effect of morphological type of extrauterine ectopic pregnancy on accuracy of preoperative ultrasound diagnosis.

OBJECTIVES: To assess the overall accuracy of transvaginal ultrasound (TVS) for diagnosis of all types of extrauterine ectopic pregnancy (EUEP) in a large group of women who were managed surgically. We also aimed to assess the positive predictive value (PPV) of TVS for each of the different ultrasound morphological types of EUEP. METHODS: This was a retrospective observational study of all pregnant women who underwent emergency surgery following ultrasound diagnosis of EUEP at a single early pregnancy unit between January 2009 and December 2017. The preoperative TVS findings were recorded, including the exact location and morphological type (Type I-V; defined using ultrasound criteria) of EUEP. TVS findings were compared with operative and histological findings. The performance of ultrasound in diagnosing EUEP overall and according to morphological type was assessed, using visual confirmation of ectopic pregnancy at surgery as the reference standard. RESULTS: A total of 26 401 women presented with early-pregnancy complications during the study period, including 1241 (4.7%; 95% CI, 4.5-5.0%) women with a conclusive diagnosis of EUEP on TVS or a presumed diagnosis based on severe pain and significant hemoperitoneum. Surgery was performed in 721/1241 (58.1%; 95% CI, 55.3-60.8%) cases, of which 710 (98.5%; 95% CI, 97.6-99.4%) had a conclusive diagnosis of EUEP on preoperative TVS. The remaining 11 women had severe pain and significant hemoperitoneum and were managed surgically on clinical grounds as an emergency, without an ectopic pregnancy having been identified on ultrasound examination. At laparoscopy, the diagnosis of EUEP was confirmed in 706/710 (99.4%; 95% CI, 98.6-99.8%) women with a positive ultrasound diagnosis and in all 11 women with a presumed ultrasound diagnosis of EUEP. The PPV of preoperative ultrasound for the diagnosis of EUEP was 99.4% (95% CI, 98.6-99.8%) with sensitivity of 98.5% (95% CI, 97.3-99.1%). There was no statistically significant difference in the accuracy of preoperative ultrasound diagnosis between the five morphological types (P = 0.76). CONCLUSIONS: The accuracy of preoperative ultrasound for diagnosis of EUEP is high. The morphological type of EUEP on TVS had no significant effect on the accuracy of preoperative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Reliability and validity of the World Health Organization reading standards for paediatric chest radiographs used in the field in an impact study of Pneumococcal Conjugate Vaccine in Kilifi, Kenya.

BACKGROUND: Radiologically-confirmed pneumonia (RCP) is a specific end-point used in trials of Pneumococcal Conjugate Vaccine (PCV) to estimate vaccine efficacy. However, chest radiograph (CXR) interpretation varies within and between readers. We measured the repeatability and reliability of paediatric CXR interpretation using percent agreement and Cohen's Kappa and the validity of field readings against expert review in a study of the impact of PCV on pneumonia. METHODS: CXRs were obtained from 2716 children admitted between 2006 and 2014 to Kilifi County Hospital, Kilifi, Kenya, with clinically-defined severe or very-severe pneumonia. Five clinicians and radiologists attended a three-day training course on CXR interpretation using a WHO standard. All CXRs were read once by two local primary readers. Discordant readings and 13% of concordant readings were arbitrated by a panel of three expert radiologists. To assess repeatability, a 5% median random sample was presented twice. Sensitivity and specificity of the primary readers' interpretations was estimated against the 'gold-standard' of the arbitrators' results. RESULTS: Of 2716 CXRs, 2 were uninterpretable and 159 were evaluated twice. The percent agreement and Kappa for RCP were 89% and 0.68 and ranged between 84-97% and 0.19-0.68, respectively, for all pathological findings. Intra-observer repeatability was similar to inter-observer reliability. Sensitivities of the primary readers to detect RCP were 69% and 73%; specificities were 96% and 95%. CONCLUSION: Intra- and inter-observer agreements on interpretations of radiologically-confirmed pneumonia are fair to good. Reasonable sensitivity and high specificity make radiologically-confirmed pneumonia, determined in the field, a suitable measure of relative vaccine effectiveness.

Caesarean scar pregnancy in the UK: a national cohort study.

OBJECTIVE: To estimate the incidence of caesarean scar pregnancy (CSP) and to describe the management outcomes associated with this condition. DESIGN: A national cohort study using the UK Early Pregnancy Surveillance Service (UKEPSS). SETTING: 86 participating Early Pregnancy Units. POPULATION: All women diagnosed in the participating units with CSP between November 2013 and January 2015. METHODS: Cohort study of women identified through the UKEPSS monthly mailing system. MAIN OUTCOME MEASURES: Incidence, clinical outcomes and complications. RESULTS: 102 cases of CSP were reported, with an estimated incidence of 1.5 per 10 000 (95% CI 1.1-1.9) maternities. Full outcome data were available for 92 women. Management was expectant in 21/92 (23%), medical in 15/92 (16%) and surgical in 56/92 (61%). The success rates of expectant, medical and surgical management were 43% (9/21), 46% (7/15) and 96% (54/56), respectively. The complication rates were 15/21 (71%) with expectant, 9/15 (60%) with medical and 20/56 (36%) with surgical management. Discharge from care (median number of days) was 82 (range 37-174) with expectant, 21 (range 10-31) with medical and 11 (range 4-49) with surgical management. CONCLUSIONS: Surgical management appears to be associated with a high success rate, low complication rate and short post-treatment follow up. TWEETABLE ABSTRACT: Surgery for CSP appears to be successful, with low complication rates and short post-treatment follow up.

Maternal pneumococcal nasopharyngeal carriage and risk factors for neonatal carriage after the introduction of pneumococcal conjugate vaccines in The Gambia.

OBJECTIVES: Pneumococcal nasopharyngeal carriage occurs early in life. However, the role of vertical transmission is not well understood. The aims of this study were to describe carriage among mothers and their newborns, and to assess for risk factors for neonatal carriage. METHODS: In a nested retrospective cohort study, we analysed data from the control arm of a randomized controlled trial conducted in The Gambia 2 to 3 years after introduction of pneumococcal conjugate vaccine (PCV) 13. Nasopharyngeal swabs were collected from 374 women and their newborns on the day of delivery, then 3, 6, 14 and 28 days later. Pneumococci were isolated and serotyped using conventional microbiologic methods. RESULTS: Carriage increased from 0.3% (1/373) at birth to 37.2% (139/374) at day 28 (p <0.001) among neonates and from 17.1% (64/374) to 24.3% (91/374) (p 0.015) among women. In both groups, PCV13 vaccine-type (VT) serotypes accounted for approximately one-third of the pneumococcal isolates, with serotype 19A being the most common VT. Maternal carriage (adjusted odds ratio (OR) = 2.82; 95% confidence interval (CI), 1.77-4.80), living with other children in the household (adjusted OR = 4.06; 95% CI, 1.90-8.86) and dry season (OR = 1.98; 95% CI, 1.15-3.43) were risk factors for neonatal carriage. Over half (62.6%) of the neonatal carriage was attributable to living with other children in the same household. CONCLUSIONS: Three years after the introduction of PCV in The Gambia, newborns are still rapidly colonized with pneumococcus, including PCV13 VT. Current strategies for pneumococcal control in Africa do not protect this age group beyond the herd effect.

Exploring the role of competition induced by non-vaccine serotypes for herd protection following pneumococcal vaccination.

The competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine-type (VT) serotype prevalence. We aimed to investigate if, consequently, the indirect protection of vaccines targeting most pneumococcal serotypes could fall short of the profound effects of current formulations. We compared three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in children younger than 5-years-old of 40%. We simulated vaccines of increasing valency by adding serotypes in order of their competitiveness and explored their ability to reduce VT carriage by 95% within 10 years after introduction. All models predicted that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage×vaccine coverage) needed to eliminate VT carriage increased with increasing valency. One model predicted this effect to be modest, while the other two predicted that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored. Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence, a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

Maternal colonization with Staphylococcus aureus and Group B streptococcus is associated with colonization in newborns.

OBJECTIVES: Although Staphylococcus aureus and Group B streptococcus (GBS) are major causes of neonatal sepsis in sub-Saharan Africa, it is unclear how these bacteria are transmitted to the neonate. METHODS: In a cohort of 377 Gambian women and their newborns, nasopharyngeal swabs were collected at delivery (day 0), and 3, 6, 14 and 28 days later. Breast milk samples and vaginal swabs were collected from the mother. Staphylococcus aureus and GBS were isolated using conventional microbiological methods. RESULTS: Most women were carriers of S. aureus (264 out of 361 with all samples collected, 73.1%) at some point during follow up and many were carriers of GBS (114 out of 361, 31.6%). Carriage of S. aureus was common in all three maternal sites and GBS was common in the vaginal tract and breast milk. Among newborns, carriage of S. aureus peaked at day 6 (238 out of 377, 63.1%) and GBS at day 3 (39 out of 377, 10.3%). Neonatal carriage of S. aureus at day 6 was associated with maternal carriage in the breast milk adjusted OR 2.54; 95% CI 1.45-4.45, vaginal tract (aOR 2.55; 95% CI 1.32-4.92) and nasopharynx (aOR 2.49; 95% CI 1.56-3.97). Neonatal carriage of GBS at day 6 was associated with maternal carriage in the breast milk (aOR 3.75; 95% CI 1.32-10.65) and vaginal tract (aOR 3.42; 95% CI 1.27-9.22). CONCLUSIONS: Maternal colonization with S. aureus or GBS is a risk factor for bacterial colonization in newborns.

The importance of physical function to people with osteoporosis.

There is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function. INTRODUCTION: There is increasing need to understand patient-centred outcomes in osteoporosis (OP) clinical research and management. This multi-method paper provides insight on the effect of OP on patients' physical function and everyday activity. METHODS: Data were collected from three sources: (1) targeted literature review on OP and physical function, conducted in MEDLINE, Embase and PsycINFO; (2) secondary thematic analysis of transcripts from patient interviews, conducted to develop a patient-reported outcome instrument. Transcripts were re-coded to focus on OP impact on daily activities and physical function for those with and without fracture history; and (3) discussions of the literature review and secondary qualitative analysis results with three clinical experts to review and interpret the importance and implications of the findings. RESULTS: Results suggest that OP, particularly with fracture, can have profound impacts on physical function/activity. These impacts accumulate over time through a cycle of impairment, as fracture leads to longer term detriments in physical function, including loss of muscle, activity avoidance and reduced physical capacity, which in turn leads to greater risk of fracture and potential for further physical restrictions. The cycle of impairment is complex, as other physical, psychosocial and treatment-related factors, such as comorbidities, fears and beliefs about physical activity and fracture risk influence physical function and everyday activity. CONCLUSION: More information on how treatments impact physical function would benefit healthcare professionals and persons with OP in making treatment decisions and improving treatment compliance/persistence, as these impacts may be more salient to patients than fracture incidence.

Psychological morbidity associated with hyperemesis gravidarum: a systematic review and meta-analysis.

BACKGROUND: Psychological illness occurring in association with hyperemesis gravidarum (HG) has been widely reported. OBJECTIVE: To determine if there is a higher incidence of psychological morbidity in women with HG compared with women without significant nausea and vomiting in pregnancy. SEARCH STRATEGY: PubMed, MEDLINE, Embase and PsychINFO were searched up to September 2015. SELECTION CRITERIA: Articles referring to psychological morbidity in relation to HG. For meta-analysis case-control studies using numerical scales to compare psychological symptoms. DATA COLLECTION AND ANALYSIS: Articles were independently assessed for inclusion by two reviewers and methodology was appraised using the Newcastle Ottawa Scale. Comparison was made using the standard mean difference (SMD) in symptom scale scores. MAIN RESULTS: In all, 59 articles were included in the systematic review, 12 of these were used in the meta-analysis. Meta-analysis of depression scale scores demonstrated a very large effect with statistically significantly higher depression scale scores in women with HG (SMD 1.22; 95% CI 0.80-1.64; P ≤ 0.01) compared with controls. Meta-analysis of anxiety scores demonstrated a large effect with statistically significantly higher anxiety disorder scale scores in women with HG (SMD 0.86; 95% CI 0.53-1.19; P ≤ 0.01). In both analyses significant heterogeneity was identified (depression and HG I2  = 94%, P ≤ 0.01; anxiety and HG I2  = 84%, P = 0.02). CONCLUSIONS: Our systematic review and meta-analysis have shown a significantly increased frequency of depression and anxiety in women with HG. The findings should prompt service development for women with HG that includes provision of psychological care and support. TWEETABLE ABSTRACT: Meta-analysis demonstrates an increase in #PsychologicalMorbidity in women with #HyperemesisGravidarum.