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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 450-454, 2023 Mar.
Article in Chinese | MEDLINE | ID: mdl-36949715

ABSTRACT

Low-dose prophylactic aspirin is widely recommended for pregnant women for the prevention of preeclampsia (PE). Although the efficacy of aspirin in preventing PE has been evaluated in many studies, due to the differences in dosage, initiation time, and screening methods for the identification of women at high risk of PE and the lack of a uniform opinion on the medication regimen of aspirin, currently in China there is no consensus on the standardized treatment scheme of aspirin for the prevention of PE in clinical guidelines. Herein, we reviewed the current available evidence and the recommendations of clinical guidelines concerning the controversies about aspirin dosage as well as the timing of starting and stopping aspirin, so as to provide further guidance for clinical practice. Based on the existing research findings on and clinical practice of using aspirin for PE prevention, we suggested that PE risk screening should be conducted at 11-13+6 weeks of gestation. In addition, the recommended dose for prophylactic use of aspirin for pregnant women at high risk of PE is 150 mg/d, and the recommended minimum effective dose is 100 mg/d. Pregnant women at high risk of PE should start taking low-dose aspirin orally before 16 weeks of pregnancy. Week 36 of gestation is considered the window of opportunity for discontinuation of low-dose aspirin.


Subject(s)
Pre-Eclampsia , Female , Pregnancy , Humans , Pre-Eclampsia/prevention & control , Pre-Eclampsia/diagnosis , Aspirin/therapeutic use , China
2.
Haemophilia ; 28(5): 720-725, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35537097

ABSTRACT

BACKGROUND: Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce. OBJECTIVE: This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII. METHODS: Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS-Haemo). The primary outcomes were the terminal half-life (t1/2 ), concentration-time profile, and time to reach an FVIII level of < 1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile. RESULTS: Twenty-five patients were recruited; their mean age was 12.3 ± 3.0 years. The t1/2 differed among patients receiving LDP of FVIII twice weekly, with a median of t1/2 was 14.8 h (IQR 12.6-16). The median time to reach an FVIII level of < 1% was 73.8 h (IQR 58.8-80.3). Most patients could maintain a trough level of FVIII > 1% longer than 48 h. At 72-96 h, patients needed a second dose of FVIII infusion because the FVIII level was < 1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96 h, depending on the individual PK profile. CONCLUSION: Our study identified inter-individual differences in the PK parameters using LDP of FVIII twice weekly. The inter-individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.


Subject(s)
Hemophilia A , Hemostatics , Adolescent , Child , Factor VIII/pharmacokinetics , Hemophilia A/complications , Hemorrhage/prevention & control , Hemostatics/therapeutic use , Humans , Indonesia
3.
Haemophilia ; 28 Suppl 4: 26-34, 2022 May.
Article in English | MEDLINE | ID: mdl-35521737

ABSTRACT

INTRODUCTION: Prophylaxis has become standard of care for persons with severe phenotype haemophilia (PWsH). However, 'standard prophylaxis' with either factor or non-factor therapies (emicizumab) is prohibitively expensive for much of the world. We sought to evaluate whether haemophilia care can be provided at a lower cost yet achieve good results using Lower dose/Lower frequency prophylaxis (LDP) and with increasing use of antifibrinolytics (Tranexamic acid and Epsilon amino caproic acid). METHODS: We identified 12 studies that collectively included 335 PWsH using LDP. Additionally, we undertook a literature search regarding the benefits of antifibrinolytics in haemophilia care. RESULTS: Identified studies show that LDP is far superior to no prophylaxis (On demand [OD] therapy) resulting in significant patient benefits. Patients on LDP showed (in comparison to patients OD) on average: 72% less total bleeds; 75% less joint bleeds; 91% less days lost from school; 77% less hospital admission days; and improved quality of life measures. These benefits come at similar or only slightly higher (< 2-fold greater) costs than OD therapy. Antifibrinolytics are effective adjunctive agents in managing bleeds (oral, nasal, intracranial, possibly other) and providing haemostasis for surgeries (particularly oral surgeries). Antifibrinolytics can substitute for more expensive factor concentrates or can reduce the use of such concentrates. There is evidence to show that antifibrinolytics may be used in conjunction with factor concentrates/emicizumab for more effective/less costly prophylaxis. CONCLUSIONS: The use of LDP along with appropriate and increased use of antifibrinolytics offers less resourced countries good options for managing patients with haemophilia.


Subject(s)
Antifibrinolytic Agents , Hemophilia A , Antifibrinolytic Agents/therapeutic use , Factor VIII/therapeutic use , Hemarthrosis , Hemophilia A/complications , Hemophilia A/drug therapy , Humans , Quality of Life
4.
West Afr J Med ; 39(1): 11-15, 2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35156361

ABSTRACT

INTRODUCTION: The evidence of benefits for prophylaxis especially low dose prophylaxis is incontestable yet most children in developing countries as Nigeria do not have access to this treatment protocol. AIM: The aim was to audit the low dose prophylaxis treatment in Nigerian children with haemophilia. METHODOLOGY: A multicentre clinical audit of five haemophilia treatment centres; University of Nigeria Teaching Hospital Enugu, Lagos University Teaching Hospital, National Hospital Abuja, University of Port Harcourt Teaching Hospital Port Harcourt, and Federal Teaching Hospital Gombe. Eighteen children with mild-severe haemophilia were enrolled into low-dose prophylaxis treatment programme. The reduction of joint bleeding, improvement of joint function and Quality of Life (QoL) during prophylaxis were analysed. RESULTS: In total 18 children - 17males and 1 female (median age 8 years) were enrolled. The median duration of observation was 7 months (range 3-15months). Seven of the children were on primary prophylaxis (41%) while 10 of the children (59%) were on secondary prophylaxis. The number of joint bleeds decreased from a total of 162 (individual range 5-20, mean 10.3) to 42 (range 0-7, mean 3.0) during the observation period with an overall reduction of 74%. Joint function improved in 94.1% of disease joints, while only 5.6% reported no improvement (due to poor compliance). School attendance improved in all subjects, sports participation and daily activity improved moderately. CONCLUSION: Low dose prophylaxis was beneficial in reduction of joint bleeds, improvement of joint function and improvement of QoL of Children with haemophilia in Nigeria.


INTRODUCTION: Les preuves des avantages de la prophylaxie en particulier la prophylaxie à faible dose est incontestable cependant en pays en développement comme le Nigeria n'ont pas accès à ce protocole de traitement. OBJECTIF: L'objectif était de vérifier le traitement prophylactique à faible dose chez les enfants nigérians atteints d'hémophilie. MÉTHODOLOGIE: Un audit clinique multicentrique de cinq centres de traitement de l'hémophilie ; L'hopital universitaire de Nigéria, Enugu Hôpital universitaire de Lagos, Hôpital national d'Abuja, l'hôpital universitaire de Port Harcourt et l'hôpital universitaire fédéral de Gombe. Dix-huit enfants atteints d'hémophilie légèresévère ont été inscrits au programme de traitement prophylactique à faible dose. La réduction des saignements articulaires, l'amélioration de la fonction articulaire et de la qualité de vie (Qo) ont été analysées. RÉSULTATS: Au total, 18 enfants - 17 garçons et 1 fille (âge médian: 8 ans) ont été recrutés. La durée médiane d'observation était de 7 mois (de 3 à 15 mois). Sept des enfants étaient sous prophylaxie primaire (41 %) et 10 enfants (59 %) étaient sous prophylaxie secondaire. Le nombre de saignements articulaires a diminué, passant d'un total de162 (fourchette individuelle 5-20, moyenne 10,3) à 42 (fourchette 0-7, moyenne 3,0), pendant la période d'observation, soit une réduction globale de 74 %. La fonction articulaire s'est améliorée dans 94,1 % des articulations malades, tandis que seulement 5,6 % n'ont signalé aucune amélioration (en raison d'une mauvaise observance). n'ont signalé aucune amélioration (en raison d'une mauvaise observance). La fréquentation scolaire s'est améliorée dans toutes les matières, la pratique du sport et l'activité quotidienne s'est améliorée modérément. CONCLUSION: La prophylaxie à faible dose s'est avérée bénéfique dans la reduction des saignements articulaires, l'amélioration de la fonction articulaire et l'amélioration de la qualité de vie des enfants atteints d'hémophilie au Nigeria. MOTS-CLÉS: Prophylaxie à faible dose, Nigeria, Hémophilie, qualité de vie, concentré de facteur VIIII.


Subject(s)
Hemophilia A , Quality of Life , Child , Clinical Audit , Female , Hemarthrosis/etiology , Hemarthrosis/prevention & control , Hemophilia A/drug therapy , Humans , Nigeria
5.
Haemophilia ; 27(2): 237-244, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33550696

ABSTRACT

OBJECTIVES: To explore the long-term joint outcomes of low-dose prophylaxis in Chinese children with severe haemophilia A and to analyse their related factors. METHODS: We retrospectively analysed follow-up data from 21 severe haemophilia A children on regular low-dose prophylaxis for 6-10 years. We used International Prophylaxis Study Group magnetic resonance imaging score (IPSG MRI score), Hemophilia Joint Health Score (HJHS), number of target joints, and Hemophilia-Specific Quality of Life Index (Haemo-QoL) to evaluate joint outcomes. Factors associated with these outcomes were evaluated by statistical analysis. RESULTS: (1) The children were 1.75 to 17 years age at prophylaxis initiation. Median prophylactic factor VIII dose was 22.9 IU/kg per week. (2) At the end of follow-up: (a) The total IPSG MRI scores were 2-24 with 90.5% children exhibiting moderate to severe joint involvement (score 7-24); (b) The HJHS ranged 2-27, with 0-10 for 46.7% children and >10 for 53.3% children. There was a positive correlation between the MRI score and HJHS (p < .05); (c) Compared to their on-demand treatment period before prophylaxis, target joints numbers decreased, and no child needed auxiliary devices to walk; (d) Joint outcomes were positively correlated with the age at initiation of low-dose prophylaxis (p < .05) and negatively correlated with the treatment dose. CONCLUSION: Long-term low-dose prophylaxis had positive effect on joint outcomes compared with on-demand treatment. However, a certain degree of joint damage remained in all children indicating the need for improving the current strategy of low-dose prophylaxis.


Subject(s)
Hemophilia A , Child , China , Factor VIII/therapeutic use , Hemarthrosis , Hemophilia A/drug therapy , Humans , Magnetic Resonance Imaging , Quality of Life , Retrospective Studies
6.
Haemophilia ; 26(5): 779-785, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32700412

ABSTRACT

BACKGROUND: In countries with limited resource, haemophilia patients have to choose low-dose prophylaxis or on-demand treatment (ODT) because of economic constraints. Whether low-dose prophylaxis can achieve better joint function outcome than ODT over long-term remains unclear. AIM: To investigate the long-term effect of low-dose tertiary prophylaxis versus ODT on joint health in severe haemophilia A children. METHODS: This was a retrospective study. We enrolled and followed 34 severe haemophilia boys in China receiving on-demand treatment (n = 18) or low-dose prophylaxis (10-15 IU/kg, 2-3 times per week) for a medium-term (6-18 months, n = 9) or longer-term (19-30 months, n = 7). We evaluated their haemophilia joint health score (HJHS) 2.1 and functional independence score in haemophilia (FISH) at baseline and at their 6-year follow-up visits. Their annual bleeding rate (ABR) and annual joint bleeding rate (AJBR) were also recorded. RESULTS: During the 6-year follow-up period, ABR and AJBR were similar between the 2 prophylaxis groups, with each of the 2 prophylaxis group rates being significantly better (lower) than the ODT group (P < .05). Compared to baseline values, evaluation at 6-year follow-up showed HJHS improvement in both prophylaxis groups, although significantly (P < .05) only in the longer-term prophylaxis group. The FISH score showed insignificant change in patients in each prophylaxis cohort, compared to significant worsening (P < .05) in the ODT group. CONCLUSION: Low-dose tertiary prophylaxis reduced ABR and AJBR of children with severe haemophilia and better maintained their functional independence by the FISH over the long term. Longer-term prophylaxis also improved their joint health status by the HJHS.


Subject(s)
Hemophilia A/drug therapy , Adolescent , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Time Factors
7.
Haemophilia ; 26(4): 615-621, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32530117

ABSTRACT

INTRODUCTION: The clinical benefits of administering low-dose prophylaxis in children with haemophilia are well established. Qualitative research describing the impact of prophylaxis on quality of life is comparatively rare in this area. AIM: The aim of this study was to investigate in children the experiences of living and becoming adjusted to haemophilia before prophylaxis, by collecting information directly from children and their parents or guardians. A further goal was to evaluate whether and how the use of low-dose prophylaxis impacts the disease experience. METHODS: A grounded theory design according to Strauss and Corbin was chosen for this study. The study was conducted in the Haemophilia Treatment Centre at Aluva, Kerala, India and involved nineteen participants (children, mothers, father and grandmothers) who were selected by theoretical sampling. Data were collected through audiotaped interviews, which included demographic and semi-structured interview questions. Data were coded and evolved into concepts and categories that lead to the emergence of theory. RESULTS: The study resulted in the construction of 'Theory of Therapeutic Metamorphosis'. It comprised two stages: stage of bondage (enduring hardships), experienced during the absence of prophylaxis or on-demand treatment and stage of freedom (deliverance/reductions, energized life/improvements and behaviour to seek prophylaxis) experienced during low-dose prophylaxis. CONCLUSION: This study illustrates the challenges faced by children with haemophilia and their families and the positive impact of low-dose prophylaxis. Further prospective research studies are required to add to the growing knowledge in this area.


Subject(s)
Grounded Theory , Hemophilia A/drug therapy , Hemophilia A/psychology , Parents/psychology , Child , Child, Preschool , Educational Status , Female , Hemophilia A/prevention & control , Humans , India/epidemiology , Interviews as Topic/methods , Male , Models, Theoretical , Qualitative Research , Quality of Life/psychology
8.
Haemophilia ; 26 Suppl 3: 9-10, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32356348

ABSTRACT

Prophylaxis is the gold standard treatment for haemophilia but requires more amount of clotting factor concentrates, than on demand therapy. Low dose prophylaxis is an alternative for countries with limited resources. There are data of evidence showing the superiority of low-dose prophylaxis than episodic treatment. Studies from China, India, Tunisia, Thailand and Indonesia reported experiences with low dose prophylaxis using outcome assessment. These studies have shown the effectiveness of various protocols regimen with once, twice or thrice injection of 10-15 UI Kg-1 per injection. These protocols allow reduction of joint bleeds and at least delay of joint damages. There is not enough long-term data nowadays, but low dose prophylaxis is certainly better than on demand therapy and should be considered as a first step of prophylaxis in some countries but not the final goal.


Subject(s)
Hemophilia A/drug therapy , Humans
9.
Haemophilia ; 25(4): 633-639, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31044491

ABSTRACT

INTRODUCTION: Prophylaxis has commonly become standard treatment for severe haemophilia patients. The World Federation of Hemophilia (WFH) recommends low-dose prophylaxis in countries with resource constraints. OBJECTIVE: To determine efficacy and safety of low-dose factor VIII (FVIII) tertiary prophylaxis compared to on-demand treatment in severe haemophilia A children in Indonesia. METHODS: Eligible patients were randomly assigned to prophylaxis and on-demand groups. Patients in the prophylaxis group received infusion of FVIII 10 IU/kg body weight, two times per week. Primary outcomes were the numbers of joint bleeding and total bleeding episodes; secondary outcomes were evidence of FVIII inhibitor, Hemophilia Joint Health Score (HJHS) and Hemophilia Early Arthropathy Detection Ultrasound (HEAD-US) score. Patients were monitored for 12 months. RESULTS: Fifty patients, all with tertiary prophylaxis, 4-18 years of age, were randomized into prophylaxis (n = 25) and on-demand (n = 25) groups. The mean follow-up time was 12.8 ± 0.86 vs 12.3 ± 0.54 months, respectively. Numbers of total and joint bleeding episodes were significantly lower in the prophylaxis group (P < 0.001, 95% CI -24.6;-10.7 and P < 0.001, 95% CI -14;-3, respectively). The prophylaxis group showed improvement of joint function (P = 0.004; CI 95% -3;-0.5); on the contrary, we found deterioration in the on-demand group (P = 0.001; CI 95% 1;3). HEAD-US scores showed improvement at month 6 in the prophylaxis group, but there was no significant difference between groups at month 12. CONCLUSION: Low-dose FVIII tertiary prophylaxis was effective in reducing joint bleeding episodes and improvement of HJHS compared to on-demand FVIII treatment in severe haemophilia A children.


Subject(s)
Factor VIII/adverse effects , Factor VIII/pharmacology , Hemophilia A/drug therapy , Hemophilia A/prevention & control , Safety , Adolescent , Child , Child, Preschool , Dose-Response Relationship, Drug , Factor VIII/therapeutic use , Female , Hemarthrosis/complications , Hemophilia A/complications , Humans , Infant , Male
10.
Haemophilia ; 25(3): 408-415, 2019 May.
Article in English | MEDLINE | ID: mdl-31050134

ABSTRACT

INTRODUCTION: The optimal treatment modality for haemophilia A is lifelong prophylaxis which is expensive and may not be implementable everywhere where factor VIII (FVIII) availability is limited. A less costly alternative to prophylaxis is low-dose prophylaxis (LDP) which was compared to conventional prophylaxis in this model-based simulation study. AIM: To explore whether LDP is motivated where standard prophylaxis is not implementable, including evaluating LDP efficacy compared to high-dose prophylaxis and investigating the potential economic benefit of individualized dosing. METHODS: For a virtual adult haemophilia A population, FVIII activity levels were simulated following alternative treatment regimens, based on a published population PK model. The regimens included very LDP, LDP and conventional prophylaxis twice and thrice weekly. The annual probability of bleeding was predicted based on the weekly time spent below 1 IU/dL, using a previously published relationship. Additionally, PK-based dose individualization was evaluated to determine FVIII savings using Bayesian forecasting. RESULTS: A treatment regimen of 10 IU/kg administered thrice weekly cost 75% less than a standard high-dose regimen and was predicted to have a 5% higher median probability of annual bleeds. PK-based dose individualization may result in further cost-savings, but implementation needs benefit versus feasibility consideration. CONCLUSION: Based on simulations, a promising LDP regimen was identified that decreased treatment costs compared with standard high-dose prophylaxis at a small increase in bleeding risk. The results indicate that LDP is advocated where the standard-of-care is on-demand treatment; however, the results should be considered in the context of any limitations of the applied models.


Subject(s)
Factor VIII/pharmacology , Hemophilia A/prevention & control , Models, Statistical , Adult , Dose-Response Relationship, Drug , Factor VIII/pharmacokinetics , Hemophilia A/metabolism , Humans
11.
Expert Rev Hematol ; 10(11): 995-1004, 2017 11.
Article in English | MEDLINE | ID: mdl-28971697

ABSTRACT

INTRODUCTION: Currently full dose prophylaxis is the standard of care in the treatment of hemophilia (World Federation of Hemophilia). However, the high costs prevent the use of standard or intermediate dose prophylaxis in China and other developing countries. Low dose prophylaxis would be a viable alternative treatment. At present global research data on the use of low dose prophylaxis is limited. Areas covered: Since 2007, China has been developing low dose prophylaxis as a high priority (90 % of moderate and severe hemophilia boys suffer joint disease by age 6 - 9). 11 studies were successfully conducted and published results showing evidence of the benefits of low dose prophylaxis to reduce joint bleeding. This new knowledge has been implemented into clinical practice in China. However the long-term outcome of arthropathy remains unclear and obstacles in execution exist. Expert commentary: In 2016, the first phenotype-based individualized prophylaxis study using four escalating low dose regimens on severe Chinese hemophilia A boys (China Individualized Prophylaxis Study (CHIP China)) launched. Using the previously published and imminent CHIP data, the goal for China is to establish an effective escalating low dose prophylaxis protocol for use in China as a standard of care.


Subject(s)
Hemophilia A/drug therapy , Adolescent , Child , Child, Preschool , China , Hemophilia A/epidemiology , Humans
12.
Haemophilia ; 23(1): 77-81, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27943510

ABSTRACT

INTRODUCTION: Low dose prophylaxis could be recommended in countries with limited resources. AIM: We report our single centre experience in children with haemophilia. PATIENTS: Fifty-five children were included in our study with a weekly median dose of 30 UI kg-1 given once, twice or thrice a week. Age of initiation of prophylaxis is 5.32 years (0.64-11.44). Outcome assessment used were number of bleeding before and after initiating prophylaxis, haemophilia joint health score (HJHS), functional independence score in haemophilia (FISH) and quality of life with the Haemo-QoL. RESULTS: Reduction of number of bleeding was clear in all patients; HJHS, FISH and Haemo-QOL were satisfactory. CONCLUSION: Low dose prophylaxis is effective and better than on-demand therapy. It should be the starting point for prophylaxis in countries with limited resources.


Subject(s)
Hemophilia A/drug therapy , Adolescent , Child , Female , Humans , Male , Tunisia
13.
Clin Appl Thromb Hemost ; 23(7): 851-858, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27920236

ABSTRACT

OBJECTIVE: This study explores the efficacy of recombinant factor VIII (rFVIII) low-dose prophylaxis in Chinese pediatric patients with severe hemophilia A from the Retrospective Study in Chinese Pediatric Hemophilia A Patients With rFVIII Contained Regular Prophylaxis (ReCARE) population. METHODS: This is additional analysis of the multicenter, retrospective ReCARE study, in which the annual bleeding rate (ABR), annual joint bleeding rate (AJBR), and safety of >12-week, low dose (10-30 IU/kg/wk) rFVIII prophylaxis divided into primary, secondary, and tertiary groups based on the joint status and joint bleeding history were analyzed. RESULTS: A total of 57 patients (median age: 8.2 [0.4-17.3] years) from the ReCARE study receiving primary (n = 3), secondary (n = 21), and tertiary (n = 33) prophylaxes were included. Low-dose prophylaxis had significant bleeding reduction in all 3 groups compared to the baseline ( S = 408.5, P < .001), with median ABR rates of -4.0 (-8.0 to -3.1), -4.0 (-24.0 to 8.0), and -13.9 (-110.6 to 20.6) in the primary, secondary, and tertiary groups, respectively, with a significant difference between the secondary and tertiary groups ( P = .008). Median AJBR reduction rates were -2.3 (-6.3 to 8.4) and -14.9 (-61.5 to 19.1) in the secondary and tertiary groups, respectively. But there was no significant difference in AJBRs between the secondary and tertiary groups ( P = .061), which was related to damaged joint status. Hence, longer prophylaxis was associated with better prevention of joint bleeding ( P = .024). CONCLUSION: Despite significant ABR/AJBR reduction in all 3 groups, the efficacy of the primary prophylaxis was better than the secondary and tertiary prophylaxes.


Subject(s)
Factor VIII/therapeutic use , Hemophilia A/drug therapy , Adolescent , Asian People , Child , Child, Preschool , Factor VIII/administration & dosage , Hemarthrosis/drug therapy , Hemarthrosis/prevention & control , Hemophilia A/complications , Humans , Infant , Premedication/methods , Recombinant Proteins/therapeutic use , Retrospective Studies , Treatment Outcome
14.
Thromb J ; 14(Suppl 1): 32, 2016.
Article in English | MEDLINE | ID: mdl-27766058

ABSTRACT

Prophylaxis is considered optimal care for hemophilia patients to prevent bleeding and to preserve joint function thereby improving quality of life (QoL). The evidence for prophylaxis is irrefutable and is the standard of care in developed nations. Prophylaxis can be further individualized to improve outcomes and cost effectiveness. Individualization is best accomplished taking into account the bleeding phenotype, physical activity/lifestyle, joint status, and pharmacokinetic handling of specific clotting factor concentrates, all of which vary among individuals. Patient acceptance should also be considered. Assessment tools (e.g. joint status imaging and function studies/scores, QoL) for determining and monitoring risk factors and outcome, as well as population PK profiling have been developed to assist the individualization process. The determinants of optimal prophylaxis include (1) factor dose/dosing frequency, hence, cost/affordability (2) bleeding triggers (physical activity/lifestyle, chronic arthropathy and synovitis) and (3) bleeding rates. Altering one determinant results in adjustment of the other two. Thus, the trough level to protect from spontaneous bleeding can be increased in patients who have greater bleeding risks; and prophylaxis to achieve zero joint bleeds is achievable through optimal individualization. Prophylaxis in economically constrained nations is limited by the ill-affordability of clotting factor concentrates. However, at least 5 studies on children and adults from Thailand, China and India have shown superiority of low dose (~5-10 IU kg-1 2-3× per week) prophylaxis over episodic treatment in terms of bleed reduction, and quality of life, with improved physical activity, independent functioning, school attendance and community participation. In these nations, the prophylaxis goals should be for improved QoL rather than "zero bleeds" and perfect joints. Prophylaxis can still be individualized to affordability. Higher protective trough level can be achieved by using smaller doses given more frequently without an increase in consumption/cost. The bleeding trigger can also be down-regulated by avoiding unnecessary injury, and by engaging in judicious strengthening exercises appropriate to the joint status to improve balance and joint stabilization. Central to the success of prophylaxis are clinics with comprehensive care that provide the necessary professional expertise, support, and counseling, to educate patients, families, and other healthcare professionals, and to support research for improved hemophilia care.

15.
Indian J Nephrol ; 19(4): 129-39, 2009 Oct.
Article in English | MEDLINE | ID: mdl-20535247

ABSTRACT

Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of both community-acquired and nosocomial infections for patients admitted to hospitals. For better management and prognosis, it is mandatory to know the possible site of infection, whether the infection is uncomplicated or complicated, re-infection or relapse, or treatment failure and its pathogenesis and risk factors. Asymptomatic bacteriuria is common in certain age groups and has different connotations. It needs to be treated and completely cured in pregnant women and preschool children. Reflux nephropathy in children could result in chronic kidney disease; otherwise, urinary tract infections do not play a major role in the pathogenesis of end-stage renal disease. Symptomatic urinary tract infections occur most commonly in women of child-bearing age. Cystitis predominates, but needs to be distinguished from acute urethral syndrome that affects both sexes and has a different management plan than UTIs. The prostatitis symptoms are much more common than bacterial prostatic infections. The treatment needs to be prolonged in bacterial prostatitis and as cure rates are not very high and relapses are common, the classification of prostatitis needs to be understood. The consensus conference convened by National Institute of Health added two more groups of patients, namely, chronic prostatitis/chronic pelvic pain syndrome and asymptomatic inflammatory prostatitis, in addition to acute and chronic bacterial prostatitis. Although white blood cells in urine signify inflammation, they do not always signify UTI. Quantitative cultures of urine provide definitive evidence of UTI. Imaging studies should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management. Treatment of cystitis in women should be a three-day course and if symptoms are prolonged, then a seven day course of antibiotics should be given. Selected group of patients benefits from low-dose prophylactic therapy. Upper urinary tract infection may need in-patient treatment. Treatment of acute prostatitis is 30-day therapy of appropriate antibiotics and for chronic bacterial prostatitis a low dose therapy for 6-12 months may be required. It should be noted that no attempt should be made to eradicate infection unless foreign bodies such as stones and catheters are removed and correctable urological abnormalities are taken care of. Treatment under such circumstances can result only in the emergence of resistant organisms and complicate therapy further.

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