Mapping domains of early life determinants of future multimorbidity across three UK longitudinal cohort studies.

Many studies use a reductionist approach to isolate the influence of one factor in childhood on multimorbidity rather than consider the combined effect of wider determinants. We explored how potential multiple early life determinants of multimorbidity can be characterised across three UK cohort studies. We used the National Child Development Study (NCDS), the 1970 British Cohort Study (BCS70), and the Aberdeen Children of the 1950s Study (ACONF) to identified early life variables that fit into 12 conceptualised domains of early life determinants of multimorbidity. Variables were assigned into 12 domains; principal component analysis reduced the dimensionality of the data and structured variables into subgroups. The data audit identified 7 domains in ACONF, 10 domains in NCDS and 12 domains in BCS70. Dominant components included maternal fertility histories within the prenatal, antenatal and birth domain, long-term illnesses within the child health domain, educational ability within the child education and health literacy domain, ethnicity within the demography domain, parental health behaviours within the transgenerational domain, housing within the socioeconomic domain and parental-child interactions within the parental-family domain. We demonstrated that if multiple large scale longitudinal studies are used, there is enough data available for researchers to consider conceptualising early life risk factors of multimorbidity across groups or domains. Such conceptualisation can help challenge the existing understanding of disease aetiology and develop new ideas for prevention of multimorbidity.

Building trust and increasing inclusion in public health research: co-produced strategies for engaging UK ethnic minority communities in research.

Patient and public involvement and engagement (PPIE) is essential for improved research outcomes and reduced research waste. To be effective, PPIE should provide opportunities for diverse groups to contribute to all research stages. However, UK ethnic minority communities remain underrepresented in research. This article describes strategies adopted in a public health research project that were effective in building trust and increasing inclusion of ethnic minority communities. The study team of researchers and PPIE partners reflects lessons learnt during the project and describe six main strategies that built meaningful levels of trust and inclusion: 1) early start to recruitment of PPIE partners; 2) relationship-focused engagement; 3) co-production and consultation activities; 4) open communication and iterative feedback; 5) co-production of project closure activities, and; 6) diverse research team. Meaningful outcomes for the community included the involvement of people from ethnic minorities as research participants and PPIE partners, community wellbeing, co-production of public health recommendations co-presented at the UK Houses of Parliament, and consortium-wide impact evidenced by the enrolment of 51 active PPIE partners. PPIE partners reflect on their research involvement, offering advice to researchers and encouraging people from ethnic minority communities to take part in research. An important message from PPIE partners is that involvement should not be restricted to projects specific to ethnic minorities but become a routine part of general population research, recognising ethnic minorities as an integral part of UK society. In conclusion, this article demonstrates that with appropriate strategies, inclusion and diversity can be achieved in public health research. We recommend researchers, practitioners and policy makers adopt these strategies when planning their public health projects.

The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of influenza vaccination during pregnancy on child health outcomes. DESIGN: Systematic review/meta-analysis. DATA SOURCES: Clinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019. METHODS: Randomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes. RESULTS: 19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15-50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%. Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old. CONCLUSIONS: This systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women. REGISTRATION: PROSPERO CRD42018102776.

Predicting childhood overweight and obesity using maternal and early life risk factors: a systematic review.

BACKGROUND: Childhood obesity is a serious public health challenge, and identification of high-risk populations with early intervention to prevent its development is a priority. We aimed to systematically review prediction models for childhood overweight/obesity and critically assess the methodology of their development, validation and reporting. METHODS: Medline and Embase were searched systematically for studies describing the development and/or validation of a prediction model/score for overweight and obesity between 1 to 13 years of age. Data were extracted using the Cochrane CHARMS checklist for Prognosis Methods. RESULTS: Ten studies were identified that developed (one), developed and validated (seven) or externally validated an existing (two) prediction model. Six out of eight models were developed using automated variable selection methods. Two studies used multiple imputation to handle missing data. From all studies, 30,475 participants were included. Of 25 predictors, only seven were included in more than one model with maternal body mass index, birthweight and gender the most common. CONCLUSION: Several prediction models exist, but most have not been externally validated or compared with existing models to improve predictive performance. Methodological limitations in model development and validation combined with non-standard reporting restrict the implementation of existing models for the prevention of childhood obesity.

Detection and genotyping of human papillomavirus in breast cancer tissues from Iraqi patients.

Studies have suggested a possible link between breast cancer pathogenesis and human papillomavirus (HPV) infection. This study in Iraq used in situ hybridization to detect the frequency and genotyping of HPV in tissue specimens from 129 patients diagnosed with malignant breast cancer, 24 with benign breast tumours and 20 healthy controls. In the breast cancer group, cocktail HPV genotypes were detected in 60 (46.5%) archived tissue blocks. Of these, genotypes 16 (55.5%), 18 (58.4%), 31 (65.0%) and 33 (26.6%) were detected. Mixed HPV genotypes 16 + 18, 16 + 18 + 31, 16 + 18 + 33, 18 + 33, 16 + 31 and 18 + 31 were found in 5.0%, 25.0%, 8.3%, 7.7%, 10.0% and 13.3% of cancer cases respectively. Only 3 benign breast tumour tissues (12.5%) and none of the healthy breast tissue specimens were HPV-DNA-positive. The detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

Detection and genotyping of human papillomavirus in breast cancer tissues from Iraqi patients

أشارت الدراسات إلى احتمال وجود ارتباط بين مسببات سرطان الثدي وبين العدوى بفيروس الورم الحليمي البشري. وقد استخدم الباحثون في هذه الدراسة التهجن في الموضع لكشف التكرار والنمط الجيني لفيروس الورم الحليمي البشري في عينات نسيجية أخذت من 129 مريضة شخص لديها سرطان خبيث في الثدي، إلى جانب 24 مريضة شخص لديها ورم سليم في الثدي و 20 سيدة كشواهد يتمتعن بالصحة. وكشف الباحثون لدى فريق المصابات بسرطان الثدي أنماطا مزيجة من فيروس الورم الحليمي البشري في 60 قطعة نسيجية محفوظة [46.5 %]. ومن بين هذه القطع النسيجية كشف الباحثون النمط الجيني 16 في [55.5 %]، والنمط الجيني 18 في [58.4 %]، والنمط الجيني 31 في [65.0 %]، والنمط الجيني 33 في [26.6 %]من الحالات. كما وجد بين حالات السرطان أنماط جينية مزيجة لفيروس الورم الحليمي البشري 16+18 في 5% من الحالات، و16+18+31 في 25.0% من الحالات، و16+18+33 في 8.3% من الحالات، و18+33 في 6.7% من الحالات و16+31 في 10% من الحالات و18+31 في 13.3% من الحالات المصابة بالسرطان ولم تكن سوى 3 عينات من نسيج الثدي المصابة بورم سليم إيجابية لدنا فيروس الورم الحليمي البشري [12.5 %]، ولم يكن هناك أي عينة من نسج الثدي السليمة إيجابية له.إن كشف الأنماط الجينية لفيروس الورم الحليمي البشري ذات التوليد العالي للورم لدى مريضات بسرطان الثدي يدعم نظرية أداء الفيروس لدور سببي في إحداث سرطان الثدي

ABSTRACT Studies have suggested a possible link between breast cancer pathogenesis and human papillomavirus (HPV) infection. This study in Iraq used in situ hybridization to detect the frequency and genotyping of HPV in tissue specimens from 129 patients diagnosed with malignant breast cancer, 24 with benign breast tumours and 20 healthy controls. In the breast cancer group, cocktail HPV genotypes were detected in 60 (46.5%) archived tissue blocks. Of these, genotypes 16 (55.5%), 18 (58.4%), 31 (65.0%) and 33 (26.6%) were detected. Mixed HPV genotypes 16 + 18, 16 + 18 + 31, 16 + 18 + 33, 18 + 33, 16 + 31 and 18 + 31 were found in 5.0%, 25.0%, 8.3%, 7.7%, 10.0% and 13.3% of cancer cases respectively. Only 3 benign breast tumour tissues (12.5%) and none of the healthy breast tissue specimens were HPV-DNA-positive. The detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

RÉSUMÉ Des études ont suggéré qu'un lien était possible entre la pathogénèse du cancer du sein et l'infection à papillomavirus humain. L'étude menée en Iraq a utilisé la méthode d'hybridation in situ pour déterminer la fréquence du papillomavirus humain et pour son génotypage dans les échantillons de tissus prélevés auprès de 129 patientes ayant reçu un diagnostic de cancer du sein malin, de 24 patientes porteuses d'une tumeur du sein bénigne et de 20 femmes témoins en bonne santé. Dans le groupe des patientes atteintes d'un cancer du sein, différents génotypes de papillomavirus humain ont été détectés dans 60 échantillons de tissus conservés (46,5 %). Parmi ceux-ci, on peut citer les génotypes 16 (55,5 %), 18 (58,4 %), 31 (65,0 %) et 33 (26,6 %). Les associations de génotypes de papillomavirus humain 16 + 18,16 + 18 + 31, 16 + 18 + 33, 18 + 31, 16 + 31 et 18 + 33 ont été observées chez 5,0 %, 25,0 %, 8,3 %, 6,7 %, 10,0 % et 13,3% des cas de cancer respectivement. Seuls trois échantillons de tissu mammaire tumoral bénin (12,5 %) étaient positifs pour l'ADN de papillomavirus humain tandis qu’aucun échantillon de tissu mammaire sain ne l’était. La détection de génotypes du papillomavirus humain hautement oncogènes chez les patientes atteintes de cancer du sein vient appuyer l'hypothèse du rôle étiologique du virus dans l'apparition d'un cancer du sein.

Knowledge, attitude and practice regarding breast cancer and breast self-examination among a sample of the educated population in Iraq.

This cross-sectional, questionnaire-based study evaluated the knowledge, attitude and practice towards breast cancer and breast self-examination (BSE) among 387 (302 females and 85 males) educated Iraqis affiliated to 2 Iraqi universities. The participants were categorized into 3 occupations: student (71.3%), teaching staff (10.3%) and administrative staff (18.3%). About half of the participants had a low knowledge score (< 50%); only 14.3% were graded as "Good" and above. Almost 75% of the participants believed that the best way to control breast cancer was through early detection and other possible preventive measures. Most participants (90.9%) had heard of BSE, the main source of information being television. However, only 48.3% practised BSE; the most common reason for not doing so was lack of knowledge of how to perform the technique correctly. Almost 84% of the female participants were willing to instruct others in the technique of BSE.

Knowledge, attitude and practice regarding breast cancer and breast self-examination among a sample of the educated population in Iraq

This cross-sectional, questionnaire-based study evaluated the knowledge, attitude and practice towards breast cancer and breast self-examination [BSE] among 387 [302 females and 85 males] educated Iraqis affiliated to 2 Iraqi universities. The participants were categorized into 3 occupations: student [71.3%], teaching staff [10.3%] and administrative staff [18.3%]. About half of the participants had a low knowledge score [< 50%]; only 14.3% were graded as [Good] and above. Almost 75% of the participants believed that the best way to control breast cancer was through early detection and other possible preventive measures. Most participants [90.9%] had heard of BSE, the main source of information being television. However, only 48.3% practised BSE; the most common reason for not doing so was lack of knowledge of how to perform the technique correctly. Almost 84% of the female participants were willing to instruct others in the technique of BSE

The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women.

OBJECTIVE: To examine the relationship between dietary supplement use during pregnancy and birth outcomes. DESIGN: A prospective birth cohort. SETTING: Leeds, UK. SAMPLE: One thousand two hundred and seventy-four pregnant women aged 18-45 years. METHODS: Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8-12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. MAIN OUTCOME MEASURES: Birthweight, birth centile and preterm birth. RESULTS: Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P = 0.02). CONCLUSIONS: Regular multivitamin-mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study's findings need confirming by other cohorts and/or trials in developed countries.

Breast cancer: demographic characteristics and clinico-pathological presentation of patients in Iraq.

Breast cancer is the commonest type of malignancy in Iraq. The study was carried out on 721 out of a total of 5044 patients (14.3%) presenting with palpable breast lumps that were diagnosed as cancer. Approximately one third of the breast cancer patients were diagnosed at age 40-49 years; 71.9% came from urban areas; and 75% were married. History of lactation was reported in 63.1% and hormonal therapy in 29%. Positive family history was recorded in 16.2%. Although the lump was detected by the patient herself in 90.6% of cases, only 32% sought medical advice within the first month. Accordingly, 47% of these patients presented in advanced stages (III and IV). The main histological type was invasive ductal carcinoma, in which pathological changes of grade II and III were observed in 56.6% and 39.9% respectively. DNA analysis showed that 80.3% of the carcinomas were aneuploid. The findings of this study justify increasing efforts for establishing comprehensive breast cancer control programmes in Iraq.

Breast cancer: demographic characteristics and clinico-pathological presentation of patients in Iraq

Breast cancer is the commonest type of malignancy in Iraq. The study was carried out on 721 out of a total of 5044 patients [14.3%] presenting with palpable breast lumps that were diagnosed as cancer. Approximately one third of the breast cancer patients were diagnosed at age 40-49 years; 71.9% came from urban areas; and 75% were married. History of lactation was reported in 63.1% and hormonal therapy in 29%. Positive family history was recorded in 16.2%. Although the lump was detected by the patient herself in 90.6% of cases, only 32% sought medical advice within the first month. Accordingly, 47% of these patients presented in advanced stages [III and IV]. The main histological type was invasive ductal carcinoma, in which pathological changes of grade II and III were observed in 56.6% and 39.9% respectively. DNA analysis showed that 80.3% of the carcinomas were aneuploid. The findings of this study justify increasing efforts for establishing comprehensive breast cancer control programmes in Iraq

Length of hospitalisation for people with severe mental illness.

BACKGROUND: In high income countries, over the last three decades, the length of hospital stays for people with serious mental illness has reduced drastically. Some argue that this reduction has led to revolving door admissions and worsening mental health outcomes despite apparent cost savings, whilst others suggest longer stays may be more harmful by institutionalising people to hospital care. OBJECTIVES: To determine the clinical and service outcomes of planned short stay admission policies versus a long or standard stay for people with serious mental illnesses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (July 2007). SELECTION CRITERIA: We included all randomised trials comparing planned short with long/standard hospital stays for people with serious mental illnesses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated fixed effects weighted mean differences (WMD). MAIN RESULTS: We included six relevant trials. We found no significant difference in hospital readmissions between planned short stays and standard care at one year (n=651, 4 RCTs, RR 1.26 CI 1.0 to 1.6). Short hospital stay did not confer any benefit in terms of 'loss to follow up compared with standard care (n=453, 3 RCTs, RR 0.87 CI 0.7 to 1.1). There were no significant differences for the outcome of 'leaving hospital prematurely' (n=229, 2 RCTs, RR 0.77 CI 0.3 to 1.8). More post-discharge day care was given to participants in the short stay group (n=247, 1 RCT, RR 4.52 CI 2.7 to 7.5, NNH 3 CI 2 to 6) and people from the short stay groups were more likely to be employed at two years (n=330, 2 RCTs, RR 0.61 CI 0.5 to 0.8, NNT 5 CI 4 to 8). Economic data were few but, once discharged, costs may be more for those allocated to an initial short stay. AUTHORS' CONCLUSIONS: The effects of hospital care and the length of stay is important for mental health policy. We found limited data, although outcomes do suggest that a planned short stay policy does not encourage a 'revolving door' pattern of admission and disjointed care for people with serious mental illness. More large, well-designed and reported trials are justified.

Colposcopy, cervical cytology and human papillomavirus detection as screening tools for cervical cancer.

A cohort of 77 women referred for routine screening or investigation of Pap test abnormality underwent colposcopic examination. Pap-stained liquid-based preparations were diagnosed and categorized according to the Bethesda system. Residual material on the sampling device was used to detect high-risk oncogenic human papillomavirus DNA. Although the colposcopic failure rate was higher than that of cytology, no lesion was missed when both methods were used together. High-risk types were recorded in 24% of patients with atypical squamous cells of undetermined significance, 45% with low-grade squamous intraepithelial lesions and 79% with high-grade squamous intraepithelial lesions--indicating that the efficacy of cytological screening can be improved by papillomavirus detection.

Colposcopy, cervical cytology and human papillomavirus detection as screening tools for cervical cancer

A cohort of 77 women referred for routine screening or investigation of Pap test abnormality underwent colposcopic examination. Pap-stained liquid-based preparations were diagnosed and categorized according to the Bethesda system. Residual material on the sampling device was used to detect high-risk oncogenic human papillomavirus DNA. Although the colposcopic failure rate was higher than that of cytology, no lesion was missed when both methods were used together. High-risk types were recorded in 24% of patients with atypical squamous cells of undetermined significance, 45% with low-grade squamous intraepithelial lesions and 79% with high-grade squamous intraepithelial lesions-indicating that the efficacy of cytological screening can be improved by papillomavirus detection

DNA proliferative index as a marker in Iraqi aneuploid mammary carcinoma.

This study estimated nuclear DNA ploidy and DNA proliferative indices (PI) in mammary ductal carcinomas from 120 Iraqi female patients. Of the examined specimens, 82.7% were aneuploid. DNA ploidy correlated significantly with histological grade and estrogen receptor content of the primary neoplasm. In aneuploid carcinomas, high PI showed a clearer association than aneuploidy with menopausal status and progesterone receptor content of the tumour. PI and percentage aneuploidy were higher in larger tumours; nodal status showed no association with these cytometric findings. Using PI, patients classified as having Auer aneuploid carcinomas can be divided into subsets with different tumour characteristics, thus improving the selection of those whose high risk, node-negative presentation makes them candidates for adjuvant systemic therapy.

Assessment of response to tamoxifen among Iraqi patients with advanced breast cancer.

Eighty-eight women presenting with locally advanced or metastatic breast cancer were treated with tamoxifen alone. Estrogen and progesterone receptors (ER and PR) were immunocytochemically analysed in mammary tumour cells obtained by fine needle sampling from 73 patients. Of the breast carcinomas, 34.2% were ER+/PR+ and 43.8% were ER-/PR-. The ER+ content increased with age in postmenopausal women. After tamoxifen treatment objective remission occurred in 39.7% of the women. The overall response rate was 53.3% in the ER+/PR- group and 73.1% in the ER+/PR+ group. However, the response elicited in a case of the ER-/PR- phenotype justified the randomized use of tamoxifen among patients in Iraq where the necessary requirements for hormone receptor assessment are almost unavailable.

DNA proliferative index as a marker in Iraqi aneuploid mammary carcinoma

This study estimated nuclear DNA ploidy and DNA proliferative indices [PI] in mammary ductal carcinomas from 120 Iraqi female patients. Of the examined specimens, 82.7% were aneuploid. DNA ploidy correlated significantly with histological grade and estrogen receptor content of the primary neoplasm. In aneuploid carcinomas, high PI showed a clearer association than aneuploidy with menopausal status and progesterone receptor content of the tumour. PI and percentage aneuploidy were higher in larger tumours; nodal status showed no association with these cytometric findings. Using PI, patients classified as having Auer aneuploid carcinomas can be divided into subsets with different tumour characteristics, thus improving the selection of those whose high risk, node-negative presentation makes them candidates for adjuvant systemic therapy

Assessment of response to tamoxifen among Iraqi patients with advanced breast cancer

Eighty-eight women presenting with locally advanced or metastatic breast cancer were treated with tamoxifen alone. Estrogen and progesterone receptors [ER and PR] were immunocytochemically analysed in mammary tumour cells obtained by fine needle sampling from 73 patients. Of the breast carcinomas, 34.2% were ER+/PR+ and 43.8% were ER-/PR-. The ER+ content increased with age in postmenopausal women. After tamoxifen treatment objective remission occurred in 39.7% of the women. The overall response rate was 53.3% in the ER+/PR- group and 73.1% in the ER+/PR+ group. However, the response elicited in a case of the ER-/PR- phenotype justified the randomized use of tamoxifen among patients in Iraq where the necessary requirements for hormone receptor assessment are almost unavailable

Fine needle aspiration cytology versus histopathology in diagnosing lymph node lesions

Fine needle aspirates [FNA] of superficial lymph nodes were obtained from 150 patients complaining of lymphadenopathy. Cytological findings were analysed in correlation with the corresponding histopathological diagnosis of the same excised nodes. Benign lesions were found in more than half of the patients [55.3%], the majority of which were nonspecific reactive hyperplasia followed by tuberculous lymphadenitis. Lymphomas constituted the main pathology in malignant involvement [26.0%], while metastatic lesions formed 16.7% and leukaemia 2.0%. The results of FNA compared favourably with those of tissue biopsies, with an accuracy rate of 89.6% for malignant lymphadenopathy. The appropriate use of FNA may obviate the need for an open biopsy