Interobserver reproducibility of cervical histology interpretation with and without p16 immunohistochemistry.

OBJECTIVES: Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project. METHODS: We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists. RESULTS: Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24. CONCLUSIONS: Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important.

CNN stability training improves robustness to scanner and IHC-based image variability for epithelium segmentation in cervical histology.

Background: In digital pathology, image properties such as color, brightness, contrast and blurriness may vary based on the scanner and sample preparation. Convolutional Neural Networks (CNNs) are sensitive to these variations and may underperform on images from a different domain than the one used for training. Robustness to these image property variations is required to enable the use of deep learning in clinical practice and large scale clinical research. Aims: CNN Stability Training (CST) is proposed and evaluated as a method to increase CNN robustness to scanner and Immunohistochemistry (IHC)-based image variability. Methods: CST was applied to segment epithelium in immunohistological cervical Whole Slide Images (WSIs). CST randomly distorts input tiles and factors the difference between the CNN prediction for the original and distorted inputs within the loss function. CNNs were trained using 114 p16-stained WSIs from the same scanner, and evaluated on 6 WSI test sets, each with 23 to 24 WSIs of the same tissue but different scanner/IHC combinations. Relative robustness (rAUC) was measured as the difference between the AUC on the training domain test set (i.e., baseline test set) and the remaining test sets. Results: Across all test sets, The AUC of CST models outperformed "No CST" models (AUC: 0.940-0.989 vs. 0.905-0.986, p < 1e - 8), and obtained an improved robustness (rAUC: [-0.038, -0.003] vs. [-0.081, -0.002]). At a WSI level, CST models showed an increase in performance in 124 of the 142 WSIs. CST models also outperformed models trained with random on-the-fly data augmentation (DA) in all test sets ([0.002, 0.021], p < 1e-6). Conclusion: CST offers a path to improve CNN performance without the need for more data and allows customizing distortions to specific use cases. A python implementation of CST is publicly available at https://github.com/TIGACenter/CST_v1.

Integrating family planning into HIV care in western Kenya: HIV care providers' perspectives and experiences one year following integration.

With high rates of unintended pregnancy in sub-Saharan Africa, integration of family planning (FP) into HIV care is being explored as a strategy to reduce unmet need for contraception. Perspectives and experiences of healthcare providers are critical in order to create sustainable models of integrated care. This qualitative study offers insight into how HIV care providers view and experience the benefits and challenges of providing integrated FP/HIV services in Nyanza Province, Kenya. Sixteen individual interviews were conducted among healthcare workers at six public sector HIV care facilities one year after the implementation of integrated FP and HIV services. Data were transcribed and analyzed qualitatively using grounded theory methods and Atlas.ti. Providers reported a number of benefits of integrated services that they believed increased the uptake and continuation of contraceptive methods. They felt that integrated services enabled them to reach a larger number of female and male patients and in a more efficient way for patients compared to non-integrated services. Availability of FP services in the same place as HIV care also eliminated the need for most referrals, which many providers saw as a barrier for patients seeking FP. Providers reported many challenges to providing integrated services, including the lack of space, time, and sufficient staff, inadequate training, and commodity shortages. Despite these challenges, the vast majority of providers was supportive of FP/HIV integration and found integrated services to be beneficial to HIV-infected patients. Providers' concerns relating to staffing, infrastructure, and training need to be addressed in order to create sustainable, cost-effective FP/HIV integrated service models.

The effect of interventions on balance self-efficacy in the stroke population: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review of clinical trials that examined the effectiveness of interventions on balance self-efficacy among individuals with stroke. DESIGN: Systematic review. SUMMARY OF REVIEW: Searches of the following databases were completed in December 2014: MEDLINE (1948-present), CINAHL (1982-present), EMBASE (1980-present) and PsycINFO (1987-present) for controlled clinical trials that measured balance self-efficacy in adults with stroke. Reference lists of selected articles were hand-searched to identify further relevant studies. REVIEW METHODS: Two independent reviewers performed data extraction and assessed the methodological quality of the studies using the Physical Therapy Evidence Database Scale. Standardized mean differences (SMD) were calculated. RESULTS: A total of 19 trials involving 729 participants used balance self-efficacy as a secondary outcome. Study quality ranged from poor (n = 3) to good (n = 8). In the meta-analysis of 15 trials that used intensive physical activity interventions, a moderate beneficial effect on balance self-efficacy was observed immediately following the programs (SMD 0.44, 95% CI 0.11-0.77, P = 0.009). In the studies that included follow-up assessments, there was no difference between groups across retention periods (eight studies, SMD 0.32, 95% CI -0.17-0.80, P = 0.20). In the four studies that used motor imagery interventions, there was no between-group difference in change in balance self-efficacy (fixed effects SMD 0.68, 95% CI -0.33-1.69, P = 0.18). CONCLUSIONS: Physical activity interventions appear to be effective in improving balance self-efficacy after stroke.

Providers' perspectives on male involvement in family planning in the context of a cluster-randomized controlled trial evaluating integrating family planning into HIV care in Nyanza Province, Kenya.

Integration of family planning (FP) services into HIV care and increasing male partner involvement in FP are being explored as strategies to reduce unmet need for contraception. Providers' views can give valuable insight into current FP care. We evaluated the perspectives of HIV care providers working at HIV clinics in Nyanza Province, Kenya, on male partner involvement in FP. This qualitative study was part of a cluster-randomized controlled trial evaluating the impact of integrating FP into HIV services on contraceptive prevalence among HIV-positive patients in Nyanza Province, Kenya. Thirty individual interviews were conducted among health-care workers at 11 HIV care facilities in Nyanza Province, Kenya. Interviews were conducted from integrated and control sites one year after implementation of FP/HIV integration. Data were transcribed and analyzed using grounded theory methods and ATLAS-ti. Providers supported male partner inclusion when choosing FP and emphasized that decisions should be made collaboratively. Providers believed that men have traditionally played a prohibitive role in FP but identified several benefits to partner involvement in FP decision-making including: reducing relationship conflicts, improving FP knowledge and contraceptive continuation, and increasing partner cohesion. Providers suggested that integrated FP/HIV services facilitate male partner involvement in FP decision-making since HIV-positive men are already established patients in HIV clinics. Some providers stated that women had a right to choose and start FP alone if their partners did not agree with using FP. Integrated FP services may be a useful strategy to help increase male participation to reduce the unmet FP need in sub-Saharan Africa. It is important to determine effective ways to engage male partners in FP, without impinging upon women's autonomy and reproductive rights.

Immediate breast reconstruction does not increase postmastectomy pain.

BACKGROUND: Postmastectomy pain syndrome (PMPS) is a recognized complication of breast surgery, with a reported prevalence of 20­52 %. We investigated whether patients having immediate reconstruction (IR) reported more long-term pain compared to those having mastectomy alone (MA). We also investigated treatment factors influencing PMPS. METHODS: In a single center, all patients who underwent MA or IR between January 2009 and June 2011 and attended for follow-up between February 2012 and July 2012 were identified. Patients were invited to complete two questionnaires, a pain intensity visual analog scale (VAS, scored 0 to 10) and the PainDetect screening tool for neuropathic pain. RESULTS: Of 318 patients due to attend, 272 (86 %) submitted complete questionnaires. Of these, 134 (49 %) women had IR (implant based n = 93, pedicled flaps n = 33, free flaps n = 8). The overall point prevalence pain was low, with 221 (81 %) reporting VAS current pain as zero. Only 8 (3 %) patients reported a VAS score above 4. Six (2 %) patients had a positive PainDetect score. The percentage of patients reporting VAS scores greater than zero and positive or borderline PainDetect scores was similar for MA and IR (VAS: 13 and 14 %, respectively; PainDetect: 6 and 11 %, respectively). Radiotherapy was the strongest predictor of neuropathic pain. CONCLUSIONS: In this cohort, the prevalence of PMPS was lower than historic reports. We find no evidence of increased overall pain intensity or chronic neuropathic pain after IR compared to MA despite additional tissue dissection and potential donor site morbidity. This adds support to the positive benefits of breast reconstruction.

Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China.

BACKGROUND: Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented. METHODS: An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models. RESULTS: From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973-1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976-1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973-1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000-2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events. CONCLUSIONS: In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.