30 research outputs found
Management of the Triple Negative Locally Advanced Breast Cancer
One out of eight women is suffering from the breast cancer. 2.3 million New cases is predicted by 2023 worldwide. Triple negative breast cancer (TNBC) is having 10–15% incidence. As categorized with the lack of estrogen, progesterone and human epidermal growth factor receptor 2 neu receptor expression. Though it presents with narrow management opportunities that makes it to be the poor prognostic as well as survival rate. The management of the TNBC includes: neoadjuvant treatment then surgery and the adjuvant treatment or the surgery as the first step and then the adjuvant treatment options accordingly. The discussion are still going on to set a management protocol for the triple negative breast cancers with positive outcome and the good disease free survival. Neoadjuvant or adjuvant chemotherapy decreases the estradiol levels and thus improves the survival. The immune check points and immune modulators are under the research and the trials are still going on to treat the TNBC with the improved outcomes. It has been concluded that the management of the TNBC, still wanting the guidelines as tumor-specific targeted therapies is in trials
ABO Blood Groups are efficient in delineating relationships across linguistic subpopulations of Pakistan
Objective: Variances in ABO blood groups frequencies across world populations make them valuable markers for studying population genetics. In this study, phenotype and gene frequencies of ABO blood group were investigated to delineate relationships across major linguistic subpopulations of Pakistan.
Materials and Methods: This is a prospective multiple cohort study design conducted during 2009-2014. Karachi with population from diverse linguistic and ethnic backgrounds was chosen as the study area. Cohorts were formed on the basis of mother tongue and termed as linguistic subpopulations. There were five major cohorts namely Balochi, Punjabi, Pashto, Sindhi and Urdu. Blood samples were collected from 2,327 unrelated individuals through random sampling within each cohort. ABO blood groups were determined using antisera. ABO gene frequencies were estimated through Bernstein methods. Cluster and Correspondence analyses were performed to explore relationships between linguistic subpopulations.
Results: Gene B was the most common across all the subpopulations except Balochi subpopulation that showed relatively higher frequency of gene A. Dendrogram of cluster analysis and biplot of correspondence analysis showed closeness of three subpopulations namely Punjabi, Sindhi and Urdu.
Conclusions: Apart from describing the frequencies of ABO blood groups, this study asserts the importance of ABO blood group in delineating the relationships between the subpopulations of Pakistan. ABO blood group has long been used as identification markers in medico-legal investigation. It is interesting to know that these markers are also efficient in delineating population genealogical structure. Randomization within a cohort, un-relatedness and a larger sample size enhance the reliability of the results.
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The possible 'calming effect' of subchronic supplementation of a standardised phospholipids carrier-based Melissa officinalis L. extract in healthy adults with emotional distress and poor sleep conditions: results from a prospective, randomized, double-blinded, and placebo-controlled clinical trial
Background: Emotional distress conditions such as depression, anxiety, stress, and poor sleep are widespread health problems that have a significant impact on people’s lives. Conventional drugs are commonly prescribed to treat emotional distress and poor sleep conditions; however, these medications have several limitations and have shown multiple side effects. Over recent years botanicals-based pharmacological agents have gained increasing research and clinical interest in the management of emotional distress and sleep disorder. Of note, Melissa officinalis L. (MO) leaf extract has demonstrated considerable neuropharmacological properties both in animal and human studies and has emerged as a promising natural “calming agent.” However, research in this area is limited, and more studies are needed to validate its efficacy in amelioration of emotional distress and poor sleep conditions.
Objectives: We aimed to assess the pharmacological effects of subchronic supplementation of an innovative standardised phospholipid carrier-based MO aqueous extract on emotional distress and poor sleep conditions.
Design: A 3-week prospective, randomised, placebo-controlled, parallel-group, double-blinded clinical trial was conducted in 100 healthy adults complaining of a moderate degree of depression, anxiety, or stress, with scores of ≥14, ≥10, and ≥19, respectively, in the self-report Depression, Anxiety, and Stress Scale (DASS-42) or poor sleep, as indicated by the score of >5 in the Pittsburgh Sleep Quality Index (PSQI) scale. In addition, the impact of emotional distress and/or poor sleep on participants’ mental wellbeing, emotional feelings, and quality of life was also assessed using the self-reported Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), Positive and Negative Affect Schedule (PANAS) scale, and quality of life (WHO-QoL-BREF) scale, respectively.
Results: Oral supplementation of 200 mg of phospholipid-based MO aqueous extract (Relissa™) tablets twice a day (i.e., 400 mg/day) for 3 weeks led to significant improvements in the depressive mood, anxiety, stress, positive and negative affect (emotional feelings), overall mental wellbeing, and quality-of-life scores (all p values <0.001). Supplementation of MO extract was well tolerated, and no treatment-emergent effects or serious adverse events were reported.
Conclusion: According to the results of this study, the phospholipid carrier-based MO aqueous extract possesses considerable neuropharmacological properties, and its supplementation may provide a promising therapeutic option for the management of moderate emotional distress and/or poor sleep conditions
A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial
Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.
Methods and results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups.
Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial
Background
Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.
Methods
In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.
Findings
Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.
Interpretation
Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.
Funding
London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
Reformation of Prisoners Through Rehabilitation; The Analysis of The Pakistani System in the Light of International Standards
Several aspects of Pakistan’s present rehabilitation structure are inconsistent with the emerging norms of International human rights law. This research suggests that the existing statutory, administrative and judicial systems should be reformed to attain exactitude in the law through maintaining a correct balance between the notion of ‘public protection’ and the ‘rights of sentenced persons’ through a fair and balanced reformation and rehabilitation centric system
Assumption of Jurisdiction by Pakistani Supreme Court in Reko Diq Case: Another Violation of International Investment Law
Purpose: This paper discusses that Pakistani judicial approach to separability, arbitrability and grounds to assume jurisdictions to decide these mattes does not sit well with the ICSID jurisprudence.
Design/Methodology/Approach: Qualitative approach has been used.
Findings: The Supreme Court’s judgment in Reko Diq is discussed in the light of awards rendered by ICSID to establish that the jurisdiction to decide the separability of arbitration agreement, arbitrability of a dispute or subject matter does not rest with a domestic court where parties have already conferred jurisdiction to determine these matters to ICSID and that Pakistani court cannot use any ground to assume jurisdiction over these matters.
Implications/Originality/Value: The paper concludes that the judicial system of Pakistan needs reforms to formalize and ascertain the role of domestic arbitration councils in alignment with the ICSID. This will help Pakistani firms competing in international markets to get necessary legal support at home in line with international standards
Arbitrability of Criminal Matters: Putting Things in Perspective
Arbitrability is one of the most contentious and widely discussed issues of arbitration. The aim of taking up this topic in this paper is to establish that the exclusion of a subject matter from the domain of arbitrator’s consideration does not mean the exclusion of each and every aspect of that subject matter. Rather some aspects of a non-arbitrable subject matter may be allowed for arbitrator’s judgment. To prove this point, the arbitrability of criminal matters is discussed to manifest that some issues springing from criminal matters may also be submitted to arbitration