A Retrospective Study of the Clinical Profile and Outcome of Adult patients with Hypoplastic Myelodysplastic Syndrome (hMDS) in a Tertiary Centre in India.

INTRODUCTION : Myelodysplastic syndromes (MDS) are a very heterogeneous group of clonal hematopoietic stem cell disorders that represents a spectrum of diseases characterized by; ineffective erythropoiesis and marrow failure limited by acute leukemias, chronic leukemias and myeloproliferative disorders at one end of the spectrum, in which hypercellular marrow is typical, to aplastic anemia at the other end. Hypoplastic Myelodysplastic syndromes (hMDS) refers to a morphological entity in which the bone marrow cellularity is low for the age (60 years). It represents approximately 10-15% of all MDS cases. Hypoplastic MDS however, does not represent a defined MDS category according to the WHO classification, but it rather denotes the morphologic status of other MDS categories. It is difficult to distinguish hMDS from acquired aplastic anemia (AA), because of considerable clinical, histologic, and cytologic similarities between the two disorders. Patients with hMDS tend to be younger, have more profound thrombocytopenia and neutropenia, lower percentage of blasts, lower probability to evolve to leukemia, and they are less likely to display abnormal karyotype, compared to patients with normocellular or hypercellular MDS. Compared to AA, hMDS have a poorer prognosis and have frequent karyotypic and FISH abnormalities and are prone to conversion to acute myeloid leukemia. The prognosis for hMDS falls between that of severe and very severe AA patients. The pathophysiology of hMDS is not very well known. Evidence suggests that immune mediated mechanisms may play a role. This subtype is most likely to respond to treatment with immunosuppressive agents. AIMS AND OBJECTIVES : 1. To analyze the clinical profile of adult patients with Hypoplastic Myelodysplastic syndrome (hMDS). 2. To assess the response to different drug therapies in patients with hMDS. 3. To identify the demographic, clinical, and laboratory parameters that can predict prognosis in hMDS. MATERIALS AND METHODS : This study protocol was approved by our Institutional Review Board (IRB). This is a retrospective analysis of patients diagnosed to have hMDS from January 1998 to June 2012. Diagnostic criteria: Hypoplastic MDS was diagnosed in patients presenting with cytopenia(s) (defined as per the recommendation in the IPSS for risk stratification in MDSs (i.e. Hemoglobin <10g%, Absolute neutrophil count <1800/mm3, and Platelets <100,000/mm3) associated with a hypoplastic bone marrow for the age, and with features of dysplasia in one or more cell lines, with or without increase in number of blasts/CD 34+ cells on bone marrow, or increase in reticulin content on bone marrow trephine, or abnormal karyotype showing malignant clonal cells (all favoring diagnosis of hMDS). Inclusion Criteria: 1. All adult patients (age≥18yrs) diagnosed to have hypoplastic myelodysplastic syndrome from January 1998 to June 2012. Exclusion Criteria: 1. Patients with other types of Myelodysplastic syndromes. 2. Patients with hMDS whose data are not retrievable. 3. Patients on drugs that can cause dysplasia (e.g. post renal transplant patients) 4. Patients with hypoplastic cytopenia(s) and positive test for PNH, or positive stress cytogenetic test (clastogenic stress-induced chromosomal breakage). RESULTS : Between January 1998 and June, 30, 2012, a total of 54413 out patients were seen in the Haematology department, of which 1225 (2.3%) were diagnosed to have primary MDS. Of this, 173 (14.1% of MDS; 0.32% of total patients) were diagnosed to have hypoplastic MDS. The year wise distribution of total MDS and hMDS is depicted in Figure:1. All patients (n=173) were included for the analysis of baseline characteristics. Out of the total 173 patients, only 111 (64.2%) who had a follow up of >8 weeks after initiation of treatment were considered ‘evaluable’ for assessment of response to treatment and for survival analysis. CONCLUSION : Hypoplastic MDS is a distinct subgroup of MDS of unknown etiology which needs to be distinguished from aplastic anemia. It is a disease associated with a relatively good prognosis, with significant response to immunosuppressive therapy and reasonable response to treatment with androgens, and a lower probability for leukemic transformation. Cytogenetic analysis at diagnosis is crucial in prognostic risk categorization of the patient. WHO classification based prognostic scoring system and revised IPSS appear to be better than IPSS in predicting survival

Client Satisfaction Towards Quality of Health Services: an Assessment at Primary Healthcare of District Gujranwala

This survey designed to evaluate the satisfaction level and the factors that affect the patient satisfaction regarding health care delivery services with the aim to improve the services in the primary health care settings of Gujranwala. A Cross Sectional Study done on randomly selected patients attending the basic health units of Gujranwala, with more than18 years of age. Pretested structured "Liker scale questionnaire" was used for data collection. Out of total respondents, 62 (41.3%) clients were satisfied with the services provided by the basic health units of Gujranwala. The factors identified to determine patient satisfaction were accessibility of services, behavior of staff, health education, level of cleanliness, drug availability and miscellaneous services. Not a single ranked area of satisfaction noticed. Client\u27s occupation and income had significant relationship with the patient satisfaction level. Gender, age, and education of clients were not contributing factors; they not affect the client satisfaction level.Less than half clients were satisfied with the services provided by the basic health units. Management of health facilities needs to improve the services

Changes in loneliness prevalence and its associated factors among Bangladeshi older adults during the COVID-19 pandemic

Aims Worldwide, loneliness is one of the most common psychological phenomena among older adults, adversely affecting their physical and mental health conditions during the COVID-19 pandemic. This study aims to assess changes in the prevalence of loneliness in the two timeframes (first and second waves of COVID-19 in Bangladesh) and identify its correlates in pooled data. Methods This repeated cross-sectional study was conducted on two successive occasions (October 2020 and September 2021), overlapping with the first and second waves of the COVID-19 pandemic in Bangladesh. The survey was conducted remotely through telephone interviews among 2077 (1032 in the 2020-survey and 1045 in the 2021-survey) older Bangladeshi adults aged 60 years and above. Loneliness was measured using the 3-item UCLA Loneliness scale. The binary logistic regression model was used to identify the factors associated with loneliness in pooled data. Results We found a decline in the loneliness prevalence among the participants in two survey rounds (51.5% in 2021 versus 45.7% in 2020; P = 0.008), corresponding to 33% lower odds in the 2021-survey (AOR 0.67, 95% CI 0.54-0.84). Still, nearly half of the participants were found to be lonely in the latest survey. We also found that, compared to their respective counterparts, the odds of loneliness were significantly higher among the participants without a partner (AOR 1.58, 95% CI 1.20-2.08), with a monthly family income less than 5000 BDT (AOR 2.34, 95% CI 1.58-3.47), who lived alone (AOR 2.17, 95% CI 1.34-3.51), with poor memory or concentration (AOR 1.58, 95% CI 1.23-2.03), and suffering from non-communicable chronic conditions (AOR 1.55, 95% CI 1.23-1.95). Various COVID-19-related characteristics, such as concern about COVID-19 (AOR 1.28, 95% CI 0.94-1.73), overwhelm by COVID-19 (AOR 1.53, 95% CI 1.14-2.06), difficulty earning (AOR 2.00, 95% CI 1.54-2.59), and receiving routine medical care during COVID-19 (AOR 2.08, 95% CI 1.61-2.68), and perception that the participants required additional care during the pandemic (AOR 2.93, 95% CI 2.27-3.79) were also associated with significantly higher odds of loneliness. However, the odds of loneliness were significantly lower among the participants with formal schooling (AOR 0.71, 95% CI 0.57-0.89) and with a family of more than four members (AOR 0.76, 95% CI 0.60-0.96). Conclusions The current study found a decreased prevalence of loneliness among Bangladeshi older adults during the ongoing pandemic. However, the prevalence is still very high. The findings suggest the need for mental health interventions that may include improving social interactions increasing opportunities for meaningful social connections with family and community members and providing psychosocial support to the vulnerable population including older adults during the pandemic. It also suggests that policymakers and public health practitioners should emphasise providing mental health services at the peripheral level where the majority of older adults reside

Tunable synthesis of Prussian Blue in exponentially growing polyelectrolyte multilayer films.

Polyelectrolyte multilayer (PEM) films have become very popular for surface functionalization and the design of functional architectures such as hollow polyelectrolyte capsules. It is known that properties such as permeability to small ionic solutes are strongly dependent on the buildup regime of the PEM films. This permeability can be modified by tuning the ionization degree of the polycations or polyanions, provided the film is made from weak polyelectrolytes. In most previous investigations, this was achieved by playing on the solution pH either during the film buildup or by a postbuildup pH modification. Herein we investigate the functionalization of poly(allylamine hydrochloride)/poly(glutamic acid) (PAH/PGA) multilayers by ferrocyanide and Prussian Blue (PB). We demonstrate that dynamic exchange processes between the film and polyelectrolyte solutions containing one of the component polyelectrolyte allow one to modify its Donnan potential and, as a consequence, the amount of ferrocyanide anions able to be retained in the PAH/PGA film. This ability of the film to be a tunable reservoir of ferrocyanide anions is then used to produce a composite film containing PB particles obtained by a single precipitation reaction with a solution containing Fe(3+) cations in contact with the film. The presence of PB in the PEM films then provides magnetic as well as electrochemical properties to the whole architecture.journal article2009 Dec 15importe

Modification of macroporous titanium tracheal implants with biodegradable structures: tracking in vivo integration for determination of optimal in situ epithelialization conditions.

Previously, we showed that macroporous titanium implants, colonized in vivo together with an epithelial graft, are viable options for tracheal replacement in sheep. To decrease the number of operating steps, biomaterial-based replacements for epithelial graft and intramuscular implantation were developed in the present study. Hybrid microporous PLLA/titanium tracheal implants were designed to decrease initial stenosis and provide a surface for epithelialization. They have been implanted in New Zealand white rabbits as tracheal substitutes and compared to intramuscular implantation samples. Moreover, a basement membrane like coating of the implant surface was also designed by Layer-by-Layer (LbL) method with collagen and alginate. The results showed that the commencement of stenosis can be prevented by the microporous PLLA. For determination of the optimum time point of epithelialization after implantation, HPLC analysis of blood samples, C-reactive protein (CRP), and Chromogranin A (CGA) analyses and histology were carried out. Following 3 weeks the implant would be ready for epithelialization with respect to the amount of tissue integration. Calcein-AM labeled epithelial cell seeding showed that after 3 weeks implant surfaces were suitable for their attachment. CRP readings were steady after an initial rise in the first week. Cross-linked collagen/alginate structures show nanofibrillarity and they form uniform films over the implant surfaces without damaging the microporosity of the PLLA body. Human respiratory epithelial cells proliferated and migrated on these surfaces which provided a better alternative to PLLA film surface. In conclusion, collagen/alginate LbL coated hybrid PLLA/titanium implants are viable options for tracheal replacement, together with in situ epithelialization.journal articleresearch support, non-u.s. gov't2012 Aug2012 03 02importe

Development of the Manchester wide-awake hand trauma service in 2020: the patient experience

From SAGE Publishing via Jisc Publications RouterHistory: epub 2021-04-24Publication status: Publishe

Polymer multilayer films obtained by electrochemically catalyzed click chemistry.

We report the covalent layer-by-layer construction of polyelectrolyte multilayer (PEM) films by using an efficient electrochemically triggered Sharpless click reaction. The click reaction is catalyzed by Cu(I) which is generated in situ from Cu(II) (originating from the dissolution of CuSO(4)) at the electrode constituting the substrate of the film. The film buildup can be controlled by the application of a mild potential inducing the reduction of Cu(II) to Cu(I) in the absence of any reducing agent or any ligand. The experiments were carried out in an electrochemical quartz crystal microbalance cell which allows both to apply a controlled potential on a gold electrode and to follow the mass deposited on the electrode through the quartz crystal microbalance. Poly(acrylic acid) (PAA) modified with either alkyne (PAA(Alk)) or azide (PAA(Az)) functions grafted onto the PAA backbone through ethylene glycol arms were used to build the PEM films. Construction takes place on gold electrodes whose potentials are more negative than a critical value, which lies between -70 and -150 mV vs Ag/AgCl (KCl sat.) reference electrode. The film thickness increment per bilayer appears independent of the applied voltage as long as it is more negative than the critical potential, but it depends upon Cu(II) and polyelectrolyte concentrations in solution and upon the reduction time of Cu(II) during each deposition step. An increase of any of these latter parameters leads to an increase of the mass deposited per layer. For given buildup conditions, the construction levels off after a given number of deposition steps which increases with the Cu(II) concentration and/or the Cu(II) reduction time. A model based on the diffusion of Cu(II) and Cu(I) ions through the film and the dynamics of the polyelectrolyte anchoring on the film, during the reduction period of Cu(II), is proposed to explain the major buildup features.journal articleresearch support, non-u.s. gov't2010 Feb 16importe

IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients

Purpose: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. Experimental design: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points. Results: Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3–38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4–43.7%) by per-protocol analysis. In those patients that achieved clinical benefit (n = 5), the median (interquartile range) duration was 9.4 months (8.1–11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5–4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%). Conclusions: The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments