Osteoarthritis: a look at pathophysiology and approach to new treatments: a review

Objective: To review old, current, emerging and potential pathophysiological mechanisms in osteoarthritis and its approach to new treatments. Data sources: Published original research work and reviews from 1995 till early 2008 were searched in English on subjects related to pathogenesis, pathophysiology and potential new approaches to treatment of osteoarthritis. Study design: Articles that emphasized the pathogenesis and pathophysiology and new treatment approaches to the management of osteoarthritis. Data extraction: Online and manual library searches. Data synthesis: Data added up and summarized. Conclusion: Although osteoarthritis is characterized by cartilage degeneration, changes also involve the synovial membrane and the subchondral bone. Evidence suggests the involvement of a number of factors in the pathogenesis of osteoarthritis, like the proteases,pro-inflammatory cytokines, nitrous oxide, calcium crystals, leptin, angiogenesis and T cells and in turn using some of these to formulate some of the potential for new treatments for osteoarthritis

Socio-demographic and clinical aspects of rheumatoid arthritis

Objective: To determine the socio-demographic profiles and some clinical aspects of patients with rheumatoid arthritis (RA).Design: Prospective, cross-sectional study.Setting: Ambulatory out- patient clinics of Kenyatta National Hospital (KNH), a public national and referral hospital.Subjects: Out of 180 patients interviewed and examined, 60 met American College of Rheumatology (ACR) diagnostic criteria of RA.Results: Of the 60 patients recruited 52 (87%) were females with male: female ratio of 1: 6.5. The mean age of patients was 41.38(± 16.8) years. There were two peaks of age of occurrence, 20-29 and 40-49 years. In 75% of the study patients, one or more of metacarpophalangeal joints of the hand were involved in the disease. Other frequently involved sites were - wrists, elbows, knees, ankles and glenohumeral joints of shoulders in a symmetrical manner. Serum rheumatoid factor was positive in 78.9% while rheumatoid nodules were present in 13.3% of the study patients. A large majority of patients (88%) had active disease with 18% having mild disease, 38% moderate activity and 32% having severe disease. Only 12% of patients had disease in remission. Forty six point seven per cent (46.7%) of the study patients were on at least one Disease Modifying anti Rheumatic Drugs (DMARD) from a selection of methotrexate, sulphasalazine, hydroxychloroquine and leflunamide. The most frequent drug combination was methotrexate plus prednisolone at 30% of the study population; while 66.7% were on oral prednisolone with 25% of the study patients taking only Non-Steroidal anti Inflammatory Drugs (NSAIDS).Conclusion: A large majority of ambulatory patients with RA had active disease. Most of’ them were sub-optimally treated, especially the use of DMARDS. About two thirds were on oral steroids. Sub-optimal therapy in relatively young patients, peak 20-29 and 40-49 years is likely to impact negatively on their disease control and quality of life

Patterns of knee, hip and hand osteoarthritis in Kenyatta National Hospital

Background: Osteoarthritis (OA) is one of the most common chronic rheumatic disorders and is associated with significant morbidity and disability. Few studies examined the spectrum of rheumatic diseases in sub-Saharan Africa. Obesity is not only a risk factor for incidence of OA but also for the progression of the disease.Objective: The aim of the study was to determine the patterns of knee, hip and hand osteoarthritis as well as obesity prevalence in the patients with established disease.Design: A cross-sectional descriptive study.Methods: Patients with knee, hip and hand osteoarthritis were examined to describe the patterns of osteoarthritis in 201 patients who fulfilled the ACR diagnostic criteria. Their body mass indices were also studied to determine the prevalence of obesity in this cohort of patients.Results: A total of 201 patients with knee, hip or hand osteoarthritis were studied. Of these participants, 77% had knee OA, 15% hip OA, 3% hand OA and 5% had combined knee and hip OA. Obese participants were 41% and 32% were overweight. There were 89 (44.3%) participants with bilateral knee or hip disease while 112(55.7%) had unilateral disease. Obesity was more common in participants with knee than in hip OA (45.3% vs 10.3% respectively) P < 0.001. The bilateral disease was higher in obese (55.2%) and overweight (44.6%) participants compared to participants with normal body mass indices (26.5%) P value < 0.007.Conclusion: Knee OA was very common and the majority of the patients were overweight and obese. Bilateral OA was more prevalent in obese and overweight participants compared to normal weight participants. Obesity is an easily modifiable risk factor for knee OA so it can be made a valid target for preventing as well as halting the progression of OA.EAOJ; Vol. 7: September 201

Peripheral arterial disease in rheumatoid arthritis patients at the Kenyatta National Hospital, Kenya

Objective: To determine the magnitude of the rosclerotic arterial disease in Rheumatoid Arthritis(RA) patients at Kenyatta National Hospital.Design: hospital based cross-sectional study.Setting: Kenyatta National Hospital Rheumatology outpatient clinic.Subjects: Rheumatoid Arthritis patients.Results: We obtained ABI measurements in 90 RA patients, among them 23(25.5% 95% CI 17.2-36.1) had obstructed lower limb arteries. Among the 23, 21(91.3%) had mild PAD, two (8.7%) had moderate PAD; none had severe PAD nor incompressible vessels. The obstruction of vessels was independent of diabetes, hypertension, dyslipidemia and cigarette smoking though these factors increased the likelihood of having PAD. Risk age( ≥45 males, ≥55 females), Established RA(> 5 year duration) and severe RA were found to be significantly associated with the likelihood of having PAD. These trends remained significant after multivariable adjustment for potential confounders. twenty five (27.7%) of the study subjects exhibited symptoms of intermittent claudication, 13(52%) of them had PAD on ABI measurements, The Edinburgh claudication questionnaire was found to have 56.5% sensitivity and 82% specificity in detectionof PAD in RA patients. Conclusion: There seems to be an association between PAD in RA with chronicity and severity of the RA. This association may support the pathogenic role of accumulated systemic inflammation in atherosclerosis. Clinicians should be alert to the possibility of impared arterial function and thus subsequent cardiovascular morbidity and mortality in this group of patients

Patterns of knee, hip and hand osteoarthritis in Kenyatta National Hospital

Background: Osteoarthritis (OA) is one of the most common chronic rheumatic disorders and is associated with significant morbidity and disability. Few studies examined the spectrum of rheumatic diseases in sub- Saharan Africa. Obesity is not only a risk factor for incidence of OA but also for the progression of the disease.Objective: The aim of the study was to determine the patterns of knee, hip and hand osteoarthritis as well as obesity prevalence in the patients with established disease.Design: A cross-sectional descriptive study.Methods: we examined patients with knee, hip and hand osteoarthritis to describe the patterns of osteoarthritis in 201 patients who fulfilled the ACR diagnostic criteria. Their body mass indices were also studied to determine the prevalence of obesity in this cohort of patients.Results: A total of 201 patients with knee, hip or hand osteoarthritis were studied. Of these participants, 77% had knee OA, 15% hip OA, 3% hand OA and 5% had combined knee and hip OA. Obese participants were 41% and 32% were overweight. There were 89 (44.3%) participants with bilateral knee or hip disease while 112(55.7%) had unilateral disease. Obesity was more common in participants with knee than in hip OA (45.3% vs 10.3% respectively) P < 0.001. The bilateral disease was higher in obese (55.2%) and overweight (44.6%) participants compared to participants with normal body mass indices (26.5%) P value < 0.007.Conclusion: Knee OA was very common and the majority of the patients were overweight and obese. Bilateral OA was more prevalent in obese and overweight participants compared to normal weight participants. Obesity is an easily modifiable risk factor for knee OA so it can be made a valid target for preventing as well as halting the progression of OA

Stratification of persons with diabetes into risk categories for foot ulceration

Background: Patients with diabetes mellitus are at a higher risk of lower extremity complications as compared to their non-diabetic counterparts.Objective: To study risk factors for diabetic foot ulcer disease and stratify patients with diabetes into risk categories for foot ulceration.Design: Cross-sectional descriptive study over five months period.Setting: Diabetic outpatient clinic, at the Kenyatta National Hospital.Subjects: Two hundred and eighteen ambulatory subjects with diabetes mellitus without active foot lesions.Results: The prevalence of previous foot ulceration was 16% while that of previous amputation was 8%. Neuropathy was present in 42% of the study subjects and was significantly associated with age, male gender, duration of diabetes, random blood sugar, systolic blood pressure and the presence of foot deformity. Peripheral arterial disease was present in 12% and showed significant association with male gender. Foot deformities were observed in 46% of study subjects and were significantly associated with age, male gender, and presence of neuropathy. Subsequently 57% were categorised into IWGDF group 0 - no neuropathy, 10% were placed in group 1- neuropathy alone, 16% were put in group 2 - neuropathy plus either peripheral arterial disease or foot deformity and 17% were placed in risk group 3 - previous foot ulceration/amputation.Conclusion: More than one third (33%) of diabetic patients were found to be at high risk for future foot ulceration (lWGDF groups 2 and 3). Published evidence exists that shows improved outcomes with interventions targeting individual patients with diabetes at high-risk of foot ulceration. Long term prospective studies to determine outcomes for the different risk categories should be carried out locally

Morbidity and CD4+ Cell Counts at Initial Presentation of a Cohort of HAART-Naive, HIV Positive Kenyan Patients: Implications to Initiating HAART

Background: Sub-Saharan Africa with under 10% of the worldfs total population accounts for 60-70% of all HIV/AIDS cases. While these patients require HAART to manage the disease, HAART is not universally available. Majority of the patients are in resource-constrained settings, have multiple co- morbidities/infections, opportunistic infections, present late for treatment and are in the advanced stages of the HIV/A}IDSinfection.Objective: To describe the CD4+ cell counts, opportunistic infections and laboratory parameters of a cohort of HIV positive, HAART-naive patients at first presentation.Design: Cross sectional, prospective, descriptive, consecutive entry study.Setting: Kisumu District Hospital wards (medical, surgical) and medical outpatient clinic, Nairobi Rheumatology Clinic, Nairobi West Hospital and the Mater Hospital between January 2001 and December 2008.Main outcome measures: Socio-demographic parameters, opportunistic infections, CD4+ cell counts and complete blood count, biochemistry, HBsAg markers and anti- HCV serostatus.Results: Eight hundred and thirty four (350 males and 484 females) patients were screened. Three hundred and seventy (94 males and 276 females) patients were excluded. Four hundred and sixty four (256 males and 208 females) patients were finally included in the study. The mean age was 37.2 }10.6 years, range (12-78). The M: F ratio was 1.2:1. The mean CD4+ cell count was 106.5 } 125.2 cells/µl manifesting severe immnosuppression. Fifteen (3.2%), 19(4.1%), 43(9.3%) and 387(83.5%) had CD4+ cell counts of > 500, 350-499, 200-349 and < 200 cells/ƒÊl respectively. The mean white blood cell count was 8.63 } 8.8 ~ 103/ml (4.8-10.8 ~ 103/µl). Over half (51.3%) patients had leucopaenia, white cell count < 4.8 ~ 103/µl, 35 (7.5%) had leucocytosis and the rest 191 (41.2%) patients had normal white blood cell counts. The mean haemoglobin level was 7.16 } 5.01 g/dl (12-18 g/dl) and 154 (33.2%) had haemoglobin level < 5g/dl manifesting severe anaemia. The patients had multiple co-morbidities and 248 (53.4%) had . 2 co-morbidities.Conclusion: The patients presented with severe immunosuppression evidenced by low CD4+ cell counts, anaemia and multiple co-morbidities. Majority presented late at which point the cost of management is high and outcomes are likely to be poor. They required HAART and prompt  management of the co-morbidities to mitigate morbidity and reduce mortality. It would be prudent to study treatment outcomes and their determinants overtime in patients with severe HIV disease. Also, requiring study is how long such patients with severe HIV disease who commence HAART would last on first line treatment before requirement of alternative treatment

Clinical and socio-demographic profile of patients on treatment for osteoporosis in Nairobi, Kenya

Background: Osteoporosis is a chronic, progressive disease of multifactorial aetiology and one of the most common metabolic bone diseases worldwide. There is a paucity of data on osteoporosis in Africa as it’s generally thought not to affect the non-Caucasian population. We sought to describe the population with osteoporosis in a Nairobi rheumatology clinic.Objective: To evaluate the clinical characteristics of patients with osteoporosis seen at a rheumatology clinic in Nairobi.Methods: Clinical, with emphasis on musculoskeletal manifestations, treatment and selected comorbidities in 56 patients diagnosed with osteoporosis were followed up and evaluated in the Nairobi Arthritis Clinic.Results: The age distribution was 31- 95 years with majority being above the age of 60 years at 71.5%. Majority were female (89.3%). The main musculoskeletal manifestations were polyarthralgia (30.4%) followed by lower back pain (19.6%) and pathological fractures (12.5%). The types of osteoporosis were grouped as primary (9%), secondary (44.6%) and post-menopausal (46.4%). The most common clinical association being rheumatoid arthritis (39.3%) followed by steroids therapy (25%). Other comorbidities included osteoarthritis, fibromyalgia, systemic lupus erythromatosus and diabetes. Seven study participants had history of fracture with lumbar spine fractures leading at 42.8%. None of the study participants were smokers. The number of patients on calcium supplements was at 71.4% and bisphosphonates was low at 32%.Conclusion: The findings of this study from age to comorbidities on osteoporosis are in keeping with literature. The number of patients on bisphosphonates was low which differed from Western literature. Persons at increased risk for osteoporosis in this set-up include post-menopausal women with debilitating chronic illness causing reduced mobilization over time and presenting with bone pains.These patients should be investigated for osteoporosis and effective treatment administered early.Keywords: Osteoporosis, Clinical profile, Nairobi, Keny

CD4 + Cell Response to Anti-Retroviral Therapy (ARTS) In Routine Clinical Care Over One Year Period in a Cohort of HAART Naive, HIV Positive Kenyan Patients

Background: Untreated HIV/AIDS leads to severe immune depletion with opportunistic                                                                    infections and other co-morbidities. Highly active anti-retroviral therapy (HAART) enhances immunity by sustained HIV- viral suppression, increase in CD4+ cell count and immune restoration. HAART reduces risk of neutropaenia, anaemia and accompanied decrease in incidence of opportunistic infections.Objectives: To study the CD4+ cell response in patients with severe HIV/AIDS disease over one year period while on HAART.Design: Observational, descriptive, longitudinal study.Setting: Kisumu District Hospital (Medical outpatient clinic, medical and surgical wards), Nairobi Rhematology clinic and The Mater Hospital between July 2001 and March 2007.Subjects: Four hundred and sixty three consenting patients were screened for the study.Intervention: The 103 patients included received HAART within one to four weeks and appropriate treatment for the opportunistic infections and other co-morbidities. Various HAART combinations including combivir/efavirenz, stavudine/lamivudine/nevirapine and triomune 30/40 (fixed dose combination of stavudine, nevirapine and lamivudine) were used. Some delayed HAART because of the co- morbidities which had to be managed first (severe anaemia, hepatitis and meningitis).Main outcome measures: CD4+ cell increase, new clinical events.Results: Four hundred and sixty three patients (256 males and 207 females) were screened. One hundred and three patients (55 males and 48 females) were included and 360 (201 males and 159 females) patients were excluded. Mean age was 37.9 ± 9.0 years range of (15-70). The mean CD4+ cell counts over the study period were 141.7 ± 176.5 (1-1022), 192.4 ± 198.5 (3-1275), 221.2 ± 178.0 (3-1300), 247.2 ± 197.7 (1-1401) and 268.6 ± 189.9 (1-1390) cells/µl at 0,3,6,9 and 12 months respectively. Nine patients had higher CD4+ cell counts > 350 cells/µl (433-1022) at baseline and higher HIV-viral RNA range between  51,830-1million copies/µl. The patients had multiple co-morbidities,namely, had tuberculosis, sepsis, cryptococcus meningitis, herpes zoster virus, four had non- Hodgkinfs lymphoma, oral candidiasis, hepatitis B virus, pneumocytis jiroveci pneumonia and HIV with renal dysfunction. Seventy (68%) patients had . 2 opportunistic infections. Mean AST, ALT and haemoglobin levels were 127.8 ± 79.8 IU/L, 157.2 ± 50.1 IU/L and 9.1 ± 4.3 g/dl respectively. No patient tested positive foranti-HCV antibodies.Conclusion: The majority of patients had advanced HIV infection at baseline. There was a slow but steady increase in CD4+ cell count over one year. However only 30(29.1%) of patients achieved immune restoration. Seventy three (70.9%) of patients still had immune depletion with low CD4+ cell counts at one year of receiving HAART. Patients with low CD4 + cell counts at baseline had a steady increase of CD4+ cells over the first six months and this emphasises the need to initiate HAART early in public health policy strategy. Expedited HAART initiation should be done in  patients with CD4+ cell counts < 350 cells/µl. Delayed HAART, at low CD4+ cell counts, is associated with poor immune recovery/restoration

Rationale and study design of a cross sectional study documenting the prevalence of Heart Failure amongst the minority ethnic communities in the UK: the E-ECHOES Study (Ethnic - Echocardiographic Heart of England Screening Study)

Background: Heart failure is an important cause of cardiovascular morbidity and mortality. Studies to date have not established the prevalence heart failure amongst the minority ethnic community in the UK. The aim of the E-ECHOES (Ethnic - Echocardiographic Heart of England Screening Study) is to establish, for the first time, the community prevalence and severity of left ventricular systolic dysfunction (LVSD) and heart failure amongst the South Asian and Black African-Caribbean ethnic groups in the UK.Methods/Design: This is a community based cross-sectional population survey of a sample of South Asian (i.e. those originating from India, Pakistan, Bangladesh) and Black African-Caribbean male and female subjects aged 45 years and over. Data collection undertaken using a standardised protocol comprising a questionnaire incorporating targeted clinical history taking, physical examination, and investigations with resting electrocardiography and echocardiography; and blood sampling with consent. This is the largest study on heart failure amongst these ethnic groups. Full data collection started in September 2006 and will be completed by August 2009.Discussion: The E-ECHOES study will enable the planning and delivery of clinically and cost-effective treatment of this common and debilitating condition within these communities. In addition it will increase knowledge of the aetiology and management of heart failure within minority ethnic communities