The experiences and beliefs of people with severe haemophilia and healthcare professionals on pain management, and their views of using exercise as an aspect of intervention: a qualitative study

Purpose: To explore the experiences, views and beliefs of people with severe haemophilia and healthcare professionals (HCPs) on approaches for pain management, as well as their views on exercise being used as an aspect of management. Methods: Taking a qualitative inquiry approach using focus groups and semi-structured interviews, participants included people with severe haemophilia living with chronic pain and haemophilia HCPs. Data were analysed using reflexive thematic analysis. Results: Fourteen men with haemophilia with a median age of 47 (range 23–73) and six haemophilia HCPs agreed to participate. Of the people with haemophilia, 11 attended two focus groups and three were interviewed over telephone. Healthcare professionals were interviewed face-to-face. Two themes were conceptualised from the data: (i) haemophilia management and pain management is discordant (imbalance between good haemophilia care but poor pain management, historical medico-social influences on pain management, the need for trust); (ii) uncertain about exercise but clear on what matters (conflicting views on exercise, the need for proof of safety, personalised care). Conclusions: Options for effective pain management remain limited and what is used is heavily influenced by beliefs and experience. Exercise as a treatment option in pain management is conceptually acceptable for people with haemophilia. Effective pain management requires understanding of individual beliefs and fears, and a personalised approach supported by knowledgeable, trusted clinicians

Physiotherapy interventions for pain management in haemophilia: A systematic review

Purpose: Approximately 35%-50% of people with haemophilia (PWH) report living with chronic musculoskeletal pain. Although exercise based rehabilitation is effective for pain in other arthritises, there are no published guidelines for management of chronic pain in PWH. This review aims to evaluate and appraise the current evidence of effectiveness of physiotherapy interventions on (a) pain intensity, (b) quality of life (QoL) and (c) function in PWH. Methods: A systematic review of five databases AMED and CINAHL, EMBASE and MEDLINE and PEDro, as well as trial registries, grey literature and hand searching key journals was completed. Included studies were critically appraised and evaluated for risk of bias. The GRADE approach was used to rate the quality of the evidence. Results: Nine trials consisting of 235 participants met the inclusion criteria. All studies had an overall risk of bias with low methodological quality. Meta-analysis was not possible due to heterogeneity across trials. Studies comparing a range of physiotherapy interventions against no intervention showed no clear beneficial effect on pain intensity or QoL. Only one study, investigating hydrotherapy or land-based exercise against control, showed positive effect for pain intensity, but rated very low on GRADE assessment. Studies comparing one physiotherapy intervention against another showed no clear benefit on pain intensity, QoL or function. LASER with exercise and hydrotherapy were shown to have some positive effects on pain intensity, but no clear benefit on function. Conclusions: At present, there is limited evidence for the use of physiotherapy interventions in addressing the issue of pain in PWH. Better designed trials with higher quality and explicit methodology along with user involvement are needed to assess the efficacy of any proposed intervention

How does a lifetime of painful experiences influence sensations and beliefs about pain in adults with severe haemophilia? A qualitative study

Purpose: To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. Methods: A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. Results: Fourteen men with a median age of 47 (range 23–73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain – an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) “My normal isn’t normal” – identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). Conclusions: Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pai

Study of serum lipid profile and magnesium in preeclampsia

Background: A comparative study of serum lipid profile and magnesium levels in normal pregnancy versus preeclampsia (PE).Methods: A prospective study done for 2 years (October 2014 to October 2016) in the Department of Obstetrics and Gynecology, Narayana medical college and hospital, a tertiary care centre, Nellore, Andhra Pradesh, India. A sample size of 200 pregnant women, recruited and divided into group A and B. group A being women with PE and group B is normal pregnant women.A10ml of venous blood was collected in the fasting state and serum collected from clotted blood to measure lipid profile, magnesium, Apo lipoprotein A-I and Apo lipoprotein B 100.Serum Lipid profile  measured by enzymatic method using commercially available kit Human (GmbH Germany) using humastar 600 chemistry analyzer (Human GmbH Germany). Serum magnesium measured by dye binding method using commercially available kit Human (GmbH Germany) using Humastar 600 chemistry analyzer (Human GmbH Germany). Serum ApoA-I and ApoB were measured by immune-turbidometry using commercial kits from Spinreact Spain. Urine albumin done by dipstick method.Results: Serum total cholesterol (TC), Triglyceride (TG), low density lipoprotein (LDL), very low-density lipoprotein (VLDL), Apo lipoprotein B 100 (Apo B100) were high and serum Magnesium, high density lipoprotein (HDL) and Apo lipoprotein A1(Apo A1) were low in the study group (group A) compared to controls (group B).Conclusions: Abnormal lipid profile (low HDL and increased TG concentration) and serum hypomagnesaemia may be contributing etiologies of preeclampsia, having good predictive value as a screening procedure for PE in high risk pregnant population

Using theory of change to co-create a programme theory for a telerehabilitation intervention for pain management in people with haemophilia

Background Improved approaches for chronic pain management are a clinical and research priority for people with haemophilia (PWH). Involving people with lived experience in the design of a complex rehabilitation intervention strengthens the credibility and plausibility of the intervention, particularly in relation to rare disorders. Here we describe using a ‘Theory of Change’ (ToC) dialogue-based stakeholder process to create a programme theory for a telerehabilitation intervention. Methods An online workshop was convened and stakeholders received a briefing document in advance. Five stakeholders took part (3 PWH and 2 physiotherapists). At the workshop the group first agreed the overall aim of the intervention. Discussions then identified the resources, activities, barriers and enablers needed to achieve this outcome. All discussions were recorded and annotated by the workshop moderator. Behaviour change techniques were mapped for inclusion in the theory. Results A programme theory and narrative report were produced. All stakeholders reviewed these for clarity and to ensure a true refection of the workshop discussions. Agreement was based on how meaningful, well-defined, do-able, plausible, credible, and testable each component was. Stakeholders highlighted the importance of issues unique to PWH. Key components included the need for physiotherapists to be knowledgeable of the condition, a range of exercises that were inclusive of all abilities, and the need for people to feel safe and supported whilst taking part. Conclusions Co-developed theory based approaches to intervention design offer an inclusive and transparent way to develop novel and meaningful interventions for people with complex health conditions. The ToC is wholly transparent in its design and content. Together with the identified behaviour change techniques, the theory informs the protocol for a feasibility study evaluating a telerehabilitation intervention. Importantly, it allows the opportunity to revise, adapt and improve the programme theory for further implementation and evaluatio

ASSOCIATION OF SERUM HOMOCYSTEINE IN DIABETIC NEUROPATHY

Aims and Objectives: The main aim of the study was to find out the association of serum homocysteine (HCY) in diabetic neuropathy patients. Methods: All the patients who were diagnosed with Type II diabetes mellitus will be included. Their serum levels of fasting blood sugar, postprandial blood sugar, glycated hemoglobin, and associated blood parameters will be assessed. Diabetic neuropathy will be confirmed using nerve conduction testing, electromyography, and quantitative sensory testing with clinically correlated. The serum HCY levels will be measured and correlated with other blood parameters. Results: Of 1000 patients, 46 were Type I diabetic and 954 were Type II. The prevalence of neuropathy in diabetic patients was 156. Mean serum HCY without diabetic neuropathy was 6.8+2.9 and serum HCY with diabetic neuropathy was 21.6+0.29 and p value was found to be 0.0017. The correlation between serum HCY and diabetic neuropathy was found to be 14.5 with p=0.001. Conclusion: There has been a significant increase of HCY in diabetic patients. It can be clearly seen that elevated serum HCY level has led to some of the complications of diabetic neuropathy

PRECLINICAL PHARMACOKINETIC EVALUATION OF VALSARTAN FLOATING TABLETS FORMUALTED USING CROSS LINKED STARCH UREA - A NEW MODIFIED STARCH

The objective of the present study is optimization of valsartan floating tablet formulation by 23 factorial design and to evaluate the optimized valsartan floating tablets for in vitro drug release, preclinical pharmacokinetics and also for in vitro – in vivo correlation (IVIVC). Valsartan is an orally active anti-hypertensive drug, majorly absorbed from stomach and upper small intestine. Formulation of sustained release floating tablets of valsartan is needed because of its poor oral bioavailability and short biological half-life. Valsartan floating tablets were formulated as per 23 factorial design and were evaluated. Valsartan floating tablets prepared as per 23 factorial design were non-disintegrating in water and aqueous acidic (pH 1.2) and alkaline (pH 7.4) fluids and were of good quality with regard to drug content, hardness, friability and suitable for controlled release. Formulations Fa, Fab, Fac and Fabc exhibited excellent floating over >12 h with a floating lag time in the range 12-40 seconds. Higher levels (20 %) of sodium bicarbonate gave shorter floating lag time. Valsartan release from the floating tablets prepared except formulation Fa was slow and spread over 12 h and dependent on the composition of the tablets. Drug release from formulation Fa was very rapid. Valsartan release from the floating tablets was by non-fickian diffusion mechanism in all the cases except Fa. In the case of formulation Fa that gave rapid release of drug fickian diffusion was the drug release mechanism. Optimization of valsartan floating tablet formulation was done taking floating lag time as the parameter for optimization. For optimization, floating lag time was taken as response (Y) and level of sodium bicarbonate as (X1), level of bees wax as (X2) and level of starch acetate as (X3). The polynomial equation describing the relationship between the response, Y and the variables, X1 , X 2 and X3 based on the observed data was found to be Y = 8.996 - 8.596 (X1) + 2.396 (X2) – 2.431 (X1 X2) + 0.561 (X3) - 0.521 (X1 X3) + 0.396 (X2 X3) - 0.271 (X1 X2 X3). Based on the polynomial equation developed, the optimized valsartan floating tablet formulation with a floating lag time of 20 seconds could be formulated employing sodium bicarbonate (160mg/tablet), beeswax (28mg/tablet) and starch acetate (10mg/tablet). The optimized formulation (Fopt) exhibited a floating time of 12-14 h with a lag time of 21 seconds fulfilling the target floating lag time set indicating validity of the optimization technique employed. Formulations Fopt and Fab prepared exhibited excellent floating characteristics (floating over 12 h with a lag time of 21 and 12seconds respectively) and good sustained release of valsartan over 12– 14h. The optimized valsartan tablets formulated at two strengths 80 mg/tablet and 40 mg/tablet gave slow, gradual and complete release of valsartan in 12h. Valsartan was absorbed rapidly from IR tablets and slowly over longer period of time from floating tablets. Based on (AUC)o α , the relative bioavailability ( BA) of Valsartan from FTs was 166.0 % when compared to Valsartan IR tablets (100%). A good level A correlation (r = 0.961) was observed between percent drug released (in vitro) and (AUC)o α (in vivo) Key words: Cross Linked starch Urea, Floating tablets, Valsartan, Optimization, Preclinical, Pharmacokinetic

FACTORIAL STUDIES ON ENHANCEMENT OF DISSOLUTION RATE AND FORMULATION OF ACECLOFENAC TABLETS EMPLOYING Î’CDAND KOLLIPHOR HS15

Aceclofenac is an effective anti inflammatory and analgesic drug. It belongs to class II under Biopharmaceutical classification system and exhibit low and variable oral bioavailability due to its poor solubility. It is practically insoluble in water and aqueous fluids and its oral absorption is dissolution rate limited. It needs enhancement in solubility and dissolution rate for improvement of its oral bioavailability and therapeutic efficacy. The objective of the present study is to enhance the dissolution rate and formulation development of aceclofenac tablets with fast dissolution characteristics employing βCD and Kolliphor HS15, a non ionic surfactant. The individual and combined effects of βCD (factor A) and Kolliphor HS15 (factor B) on the dissolution rate of aceclofenac from solid inclusion complexes and their tablets were evaluated in a series of 22 factorial experiments. The feasibility of formulating aceclofenac - βCD-Kolliphor HS15 inclusion complexes into tablets with fast dissolution rate characteristics was also investigated. Kolliphor HS15 has not been investigated earlier for this purpose. The individual and combined effects of βCD and Kolliphor HS15 in enhancing the dissolution rate and dissolution efficiency of aceclofenac from solid inclusion complexes and their tablets were highly significant (P < 0.01). The dissolution of aceclofenac was rapid and higher in the case of aceclofenac- βCD and aceclofenac- βCD - Kolliphor HS15 complexes prepared when compared to aceclofenac pure drug. β CD alone gave a 8.66 fold increase and in combination with Kolliphor HS15 it gave 9.85 fold increase in the dissolution rate of (K1) of aceclofenac. Aceclofenac –βCD – Kolliphor HS15 inclusion complexes could be formulated into compressed tablets by wet granulation method and the resulting tablets also gave rapid and higher dissolution of aceclofenac. Aceclofenac tablets formulated with βCD and Kolliphor HS15 individually gave 4.75 and 6.1 fold increase in the dissolution rate and those containing drug - βCD -Kolliphor HS15 complex gave much higher enhancement (21.35 fold) in the dissolution rate when compared to tablets formulated with aceclofenac pure drug. Combination of βCD and Kolliphor HS15 gave much higher enhancement in the dissolution rate of aceclofenac tablets than is possible with them individually. A combination of βCD with Kolliphor HS15 is recommended to enhance the dissolution rate in the formulation development of aceclofenac tablets with fast dissolution rate characteristics

OPTIMIZATION OF IRBESARTAN TABLET FORMULATION BY 23 FACTORIAL DESIGN

Irbesartan, a widely prescribed anti hypertensive drug belongs to class II under BCS classification and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It needs enhancement in the dissolution rate in its formulation development. Complexation with β-cyclodextrin (βCD) and use of Crospovidone and PVP K 30 are tried for enhancing the dissolution rate of irbesartan in its formulation development. The objective of the present study is optimization of irbesartan tablet formulation employing Crospovidone, βCD and PVP K 30 by 23 Factorial design. Formulation of irbesartan tablets with NLT 85% dissolution in 15 min employing Crospovidone, βCD and PVP K 30 was optimized by 23 Factorial design. Eight irbesartan tablet formulations were prepared using selected combinations of the three Factors as per 23 Factorial designs. Irbesartan tablets were prepared by direct compression method and were evaluated for drug content, hardness, friability, disintegration time and dissolution rate characteristics. The dissolution rate (K1) values were analysed as per ANOVA of 23 Factorial design to find the significance of the individual and combined effects of the three Factors (βCD, Crospovidone and PVP K 30) involved on the dissolution rate of irbesartan tablets formulated. The individual and combined effects of βCD, Crospovidone and PVP K 30 on the dissolution rate (K1) of irbesartan tablets are highly significant (P<0.01). Irbesartan tablet formulation (PFac), disintegrated rapidly with in 1 min and gave very rapid dissolution of irbesartan,100% in 15 min. Higher levels of βCD and lower levels of Crospovidone gave low dissolution rates of irbesartan tablets. The increasing order of dissolution rate (K1) observed with various formulations was CFac> CFa>CFab>CFabc> CF1> CFbc> CFb> CFc. The polynomial equation describing the relationship between the response i. e. percent drug dissolved in 15 min (Y) and the levels of Crospovidone (X1),βCD (X2) and PVP K 30 (X3) based on the observed results is Y = 58.57+34.54 (X1) - 1.89(X2) – 3.60 (X1 X2) -1.82 (X3) +1.50 (X1 X3) + 3.13 (X2 X3) - 4.87 (X1 X2 X3). Based on the above polynomial equation, the optimized irbesartan tablet formulation with NLT 85% dissolution in 15 min could be formulated employing Crospovidone at 27.70% of drug content, βCD at 1:4 ratio of drug: βCD and PVP K 30 at 1% of drug content. The optimized irbesartan tablet formulation gave 86.18 % dissolution in 15 min fulfilling the target dissolution set. The dissolution profile of the optimized Irbesartan tablet formulation was similar to that of commercial brand (IROVEL-150). Hence the formulation of irbesartan tablets with NLT 85% dissolution in 15 min could be optimized by 23 Factorial design