Detection of Mismatch Repair and Microsatellite Instability in Colorectal Cancer Patients

Introduction:  Colorectal cancer is the third most common cancer worldwide. Microsatellite instability (MSI) contributes to be one of the main mechanisms in colorectal cancer. Individuals with MSI tumors have loss of expression of one or more Mismatch Repair proteins. MSI tumors have better survival rate than microsatellite stable (MSS) tumors, poor response to 5FU-based adjuvant chemotherapy and relatively successful immunotherapy in metastatic MSI tumors. Immunohistochemistry recognizes altered gene by recognizing loss of its protein product. Based on the presence or absence of Mismatch repair proteins, groups are classified into Mismatch repair proficient (MMR-p) and Mismatch repair deficient (MMR-d).  Aim:  To investigate the immunohistochemical profile of Mismatch repair proteins namely: hMLH1, hMSH2, hMSH6, and hPMS2 in surgically resected colorectal cancer specimens.  Materials and Method:  A total of 76 cases were selected from the Histopathology Department of HTAA to determine MMR protein expression status. Cases were either MMR-p or MMR-d. Results:  Of the specimens which were properly immunostained, seventeen out of seventy-six cases (22.37%) showed loss of one or more MMR proteins expression and thus were MMR-d. MLH1, MSH2, MSH6 and PMS2 protein expression was detected as 85.53% (65/76), 81.6% (62/76), 88.16% (67/76), and 76.32% (58/76), respectively. Conclusion: Mismatch repair proteins profile should be done using immunohistochemistry in  local laboratories on these selected cases before referring for the expensive molecular test

Comparing effectiveness of two client follow-up approaches in sustaining the use of Long Acting Reversible Contraceptives (LARC) among the underserved in rural Punjab, Pakistan : a study protocol and participants' profile

Background: Pakistan observes a very high i.e. 37 percent modern contraceptive method related discontinuation rates within 12 months of their initiation. And almost 10 percent of these episodes of discontinuation happened due to the side effects or health concerns experienced by the women. Most importantly, it was noted that more than 12,000 first-level care facilities are located in the rural areas, including rural health centers, basic health units, and family welfare centers, but more than 30% of these facilities are nonfunctional. This paper presents a study protocol and participants' profiling of a prospective cohort follow-up to compare the effectiveness of household based and telephonic approaches in sustaining the use of Long Acting Reversible Contraceptives (LARC) whilst to facilitate lowering method related discontinuation and increasing switching amongst the contraceptive users. Methods: A 12-month multi-centre, non-inferiority prospective user follow-up is employed using three different study categories: a) household based follow-up; b) telephonic follow-up; and c) passive or need-based follow-up along with the hypothetical assumption that the telephonic client follow-up is not inferior to the household based follow-up by continuation rate of LARC and the telephonic follow-up is less-costly than the household based client follow-up. This follow-up will be conducted in 22 health facilities -(16 rural and 6 urban based facilities) in district Chakwal. The first two study categories will receive scheduled but different follow-up from the field workers at 1, 3, 6, 9, and 12 month while the third one i.e. the 'passive or need-based follow-up' will serve as a control group. Using sampling software PASS 11, it was estimated to have 414 clients in each study category and around 1366 clients will be recruited to account for 10% attrition rate. Discussion: The study will help us to examine a more convenient method of effective follow-up for managing side effects, decreasing method discontinuation and increasing switching amongst users. The study information will also facilitate to develop a robust, effective and efficient mechanism for client follow-up to promote the continuation rates of LARC methods. The follow-up results and lessons learnt will be widely shared with stakeholders for their implementation and streamlining in health system

Clinicopathological Characteristics of Breast Carcinoma in Premenopausal Women

Background: Breast cancer is one of the leading causes of mortality world-wide. The objective of this study was to see the pattern and characteristics of carcinoma breast in premenopausal women reporting at a tertiary care hospital.Material and Methods: This cross-sectional study was conducted at surgical unit of Pakistan Institute of Medical Sciences (PIMS), Islamabad from May 2012 to April 2015. A total of 144 female patients were admitted during this period as diagnosed cases of carcinoma breast. Of these patients, all cases of breast carcinoma diagnosed in premenopausal women were selected and assessed for tumor type, TNM classification and involved breast quadrants.Results: Out of 144 patients 70 (48.6%) cases of carcinoma breast were reported in premenopausal women. The ages ranged from 14 to 48 years with a mean age of 33 ± 7.95 years. According to TNM classification, 2.9% patients were in T1, 25.7% were in T2, 32.9% were in T3 and 38.6% were in T4. Similarly, 37.1% patients presented with a nodal status of N0, 38.1% with N1, 21.4% with N2 and 2.9% with N3. Out of 70 patients, 11 (15.7%) presented with distant metastasis (M1) at the time of diagnosis. The upper outer quadrant of breast (32.9%) was most commonly involved site, followed by upper inner, lower outer and lower inner quadrants, respectively. Most common tumor type was invasive ductal carcinoma (85.7%), followed by invasive lobular carcinoma (7.1%), papillary carcinoma (4.3%), medullary carcinoma (1.4%) and malignant phylloides (1.4%). Regarding exposure to risk factors of breast cancer in these patients, 35.7% women did not breast feed and 27.1% were nulliparous. There was no history of use of oral contraceptive pills in 82.8% and positive family history was reported in 27.1% patients.Conclusions: Late presentation with advanced disease in premenopausal women is more common in our part of the world as compared to international literature. More studies on larger sample sizes should be carried out to validate these findings

Determinants of method switching among social franchise clients who discontinued the use of intrauterine contraceptive device

Introduction: Women who do not switch to alternatemethods after contraceptive discontinuation, for reasons other than the desire to get pregnant or not needing it, are at obvious risk for unplanned pregnancies or unwanted births. This paper examines the factors that influence women to switch from Intrauterine Contraceptive Device (IUCD) to other methods instead of terminating contraceptive usage altogether. Methods: The data used for this study comes from a larger cross-sectional survey conducted in nine (9) randomly selected districts of Sindh and Punjab provinces of Pakistan, during January 2011. Using Stata 11.2, we analyzed data on 333 women, who reported the removal of IUCDs due to reasons other than the desire to get pregnant. Results: We found that 39.9% of the women do not switch to another method of contraception within one month after IUCD discontinuation. Use of contraception before IUCD insertion increases the odds for method switching by 2.26 times after removal. Similarly, postremoval follow-up by community health worker doubles (OR = 2.0) the chances of method switching. Compared with women who received free IUCD service (via voucher scheme), the method switching is 2.01 times higher among women who had paid for IUCD insertion. Conclusion: To increase the likelihood of method switching among IUCD discontinuers this study emphasizes the need for postremoval client counseling, follow-up by healthcare provider, improved choices to a wider range of contraceptives for poor clients, and user satisfaction

Antecedents and Outcomes of Intimate Co-creation: A Qualitative Inquiry

This qualitative research study aims at re-conceptualizing intimate co-creation on the basis of a qualitative data analysis. Hence, along with a latest conceptualization, theory of intimation co-creation has been empirically examined in this study. Based on the qualitative research approach of interpretive phenomenological analysis, qualitative data obtained from eight in-depth interviews was transcribed and coded in QDA Miner Lite software for analysis. Results found that five emerging themes represent the phenomenon of intimate co-creation. Furthermore, the contribution of this study was that a new research framework on intimate co-creation has been developed in which antecedents and potential outcomes of intimate co-creation have been identified. Propositions have been given as well to elaborate the relationship of antecedents and outcomes of intimate co-creation for future research direction

Where you end and I begin: A new scale development on intimate co-creation

Purpose: Built upon the theories of psychological ownership, personal intimacies, and interpersonal relationship; the concept of intimate co-creation was conceptually theorized in the recent management literature. Intimate co-creation typically occurs at the dyadic level often for the creative task engagements and has a spillover effect on groups and teams. However, there is no measurement scale on intimate co-creation available in the management literature. Methodology: The current study has addressed this literature gap by developing a new measurement scale on intimate co-creation. Best practices for new measurement scale development as available in the management literature were followed. A qualitative study was conducted first to determine the dimensional structure of intimate co-creation and an initial pool of 72 items. Scale development experts’ review of the measurement scale, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) abetted in finalizing a 14 items measurement scale with four dimensions of intimate co-creation. Findings: This new measurement scale development is a milestone for further empirical research on intimate co-creation as it is the first-ever measurement scale on intimate co-creation. Conclusion: This is the first-ever measurement scale on intimate co-creation that is available for future researchers to empirically validate the concept of intimate co-creatio

Knowledge, attitudes and practices survey on organ donation among a selected adult population of Pakistan

Background: To determine the knowledge, attitudes and practices regarding organ donation in a selected adult population in Pakistan. Methods: Convenience sampling was used to generate a sample of 440, 408 interviews were successfully completed and used for analysis. Data collection was carried out via a face to face interview based on a pre-tested questionnaire in selected public areas of Karachi, Pakistan. Data was analyzed using SPSS v. 15 and associations were tested using the Pearson\u27s Chi square test. Multiple logistic regression was used to find independent predictors of knowledge status and motivation of organ donation. Results: Knowledge about organ donation was significantly associated with education (p = 0.000) and socioeconomic status (p = 0.038). 70/198 (35.3%) people expressed a high motivation to donate. Allowance of organ donation in religion was significantly associated with the motivation to donate (p = 0.000). Multiple logistic regression analysis revealed that higher level of education and higher socioeconomic status were significant (p \u3c 0.05) independent predictors of knowledge status of organ donation. For motivation, multiple logistic regression revealed that higher socioeconomic status, adequate knowledge score and belief that organ donation is allowed in religion were significant (p \u3c 0.05) independent predictors. Television emerged as the major source of information. Only 3.5% had themselves donated an organ, with only one person being an actual kidney donor. Conclusion: Better knowledge may ultimately translate into the act of donation. Effective measures should be taken to educate people with relevant information with the involvement of media, doctors and religious scholars

Manipulating the magnetization direction of transverse domain walls in Permalloy/Ir strips using nanosecond current pulses

Using magnetic force microscopy and micromagnetic simulations, we studied the effect of Oersted magnetic fields on the chirality of transverse magnetic domain walls in Fe$_{20}$Ni$_{80}$/Ir bilayer nanostrips. Applying nanosecond current pulses with a current density of around $2\times10^{12}$ A/m$^2$, the chirality of a transverse domain wall could be switched reversibly and reproducibly. These current densities are similar to the ones used for current-induced domain wall motion, indicating that the Oersted field may stabilize the transverse wall chirality during current pulses and prevent domain wall transformations

Assessing predictors of contraceptive use and demand for family planning services in underserved areas of Punjab province in Pakistan: results of a cross-sectional baseline survey

Background: Although Pakistan was one of the first countries in Asia to launch national family planning programs, current modern contraceptive use stands at only 26% with a method mix skewed toward short-acting and permanent methods. As part of a multiyear operational research study, a baseline survey was conducted to understand the predictors of contraceptive use and demand for family planning services in underserved areas of Punjab province in Pakistan. This paper presents the baseline survey results; the outcomes of the intervention will be presented in a separate paper after the study has been completed. Method: A cross-sectional baseline household survey was conducted with randomly selected 3,998 married women of reproductive age (MWRA) in the Chakwal, Mianwali, and Bhakkar districts of Punjab. The data were analyzed on SPSS 17.0 using simple descriptive and logistic regression. Results: Most of the women had low socio-economic status and were younger than 30 years of age. Four-fifths of the women consulted private sector health facilities for reproductive health services; proximity, availability of services, and good reputation of the provider were the main predicators for choosing the facilities. Husbands were reported as the key decision maker regarding health-seeking and family planning uptake. Overall, the current contraceptive use ranged from 17% to 21% across the districts: condoms and female sterilization were widely used methods. Woman’s age, husband’s education, wealth quintiles, spousal communication, location of last delivery, and favorable attitude toward contraception have an association with current contraceptive use. Unmet need for contraception was 40.6%, 36.6%, and 31.9% in Chakwal, Mianwali, and Bhakkar, respectively. Notably, more than one fifth of the women across the districts expressed willingness to use quality, affordable long-term family planning services in the future. Conclusion: The baseline results highlight the need for quality, affordable long-term family planning services close to women’s homes. Furthermore, targeted community mobilization and behavior change efforts can lead to increased awareness, acceptability, and use of family planning and birth spacing services

Evolving Migration Trends from Afghanistan: Management andHonourable Repatriation of Afghan Refugees in Pakistan

Since 1979, Pakistan has been a key player in the management of Afghan refugees despite challenging economic and security conditions. The repatriation efforts in the past could not bring conclusive results as a significant population still live in Pakistan. The outbreak of COVID 19 has increased their vulnerability due to inadequate quarantine and health facilities. The positive political developments by way of new elections and a political settlement with the Taliban provide an opportunity for honourable repatriation of Afghan refugees. This article investigates the dilemma in the management of Afghan refugees in Pakistan and suggests a viable course of action for their honourable repatriation to Afghanistan