Delayed diagnosis and treatment of rheumatoid arthritis in Sarawak General Hospital.

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder characterised by symmetrical polyarthritis which leads to damage of joints if untreated. Early diagnosis and treatment of RA to achieve tight control of the disease will improve outcome and prevent disability. OBJECTIVE: We aimed to examine the delays in the diagnosis of RA in patients presenting to the Rheumatology Unit, Sarawak General Hospital (SGH). METHODS: Data on demographics and various delays were collected from the medical records from January 2015 until March 2018. Patient delay is defined as from the time onset of symptom to the first primary care presentation. Primary care delay is defined as from the first primary care presentation to referral to rheumatology. Rheumatology delay is defined as from rheumatology referral to appointment at the rheumatology clinic. Disease modifying anti-rheumatic drugs (DMARDS) delay is defined as from the rheumatology clinic appointment to starting DMARDS. Total delay is from symptom onset to starting DMARDS. RESULTS: There were 84 new patients diagnosed with rheumatoid arthritis, out of which 66 were females (78.6%). The mean age was 54.1±12.0 years. Only 19 patients (22.6%) were treated with DMARDS within 12 weeks of symptom onset. The median time for patient delay was four weeks (Interquartile range (IQR) 2-20 weeks), while the median time primary care delay was 11 weeks (IQR 4-24 weeks). The median time for rheumatology delay was zero weeks (IQR 0- 1 week) and the DMARDS delay was zero week (IQR 0). The median time from symptom onset to DMARDS initiation was 23.5 weeks (IQR 13.25-51 weeks). CONCLUSION: The delays in the diagnosis of rheumatoid arthritis were mainly from the patient and primary care.

Treat-to-target (T2T) of serum urate (SUA) in gout: a clinical audit in real-world gout patients.

Treat-to-target (T2T) for gout has been established recently to improve its management, which has been reported to be sub-optimal with significant gaps between the goals of treatment and day-to-day clinical practice. T2T recommended a goal of serum urate (SUA) target of <360 µmoI/L in all patients with gout and <300 µmoI/L in patients with tophaceous or severe gout. T2T strategy was applied in the management of gout patients in two Rheumatology clinics from 1 January 2016 onwards. We performed a clinical audit to assess T2T of SUA in gout patients and to identify causes for failure to achieve target SUA among them. There were a total of 304 patients for our analysis. They were of multi-ethnic origin with male predominance (88.8%). They had a mean age of 57.7+13.7 years and mean disease duration of 10.1+8.7 years. The most common comorbidities were hypertension (76.2%), dyslipidemia (52.5%) and diabetes mellitus (DM) (27.4%). Our patients' body mass indexes showed that 47.7% were obese while 34.2% were overweight. Up to 62.4% of our patients had tophi and 42.6% had joint deformities. Only 34.9% of patients achieved target SUA. Nonadherence (52.3%) was the main reason identified for failure to achieve target SUA. The independent predictors for failure to achieve target SUA were nonadherence (HR=7.84, p=0.000) and presence of tophi (HR=1.95, p=0.001).

Systemic lupus erythematosus pregnancies: ten-year data from a single centre in Malaysia.

We performed a retrospective study of all systemic lupus erythematosus (SLE) pregnancies during a 10-year period (2006-2015) to describe the clinical features, maternal and foetal outcomes in our centre. There were 115 pregnancies in 86 women with SLE. Our patients had a mean age of 29.1 years (SD 5.80) and a mean disease duration of 44.63 months (SD 41.17). Fifteen patients had antiphospholipid syndrome (APS). Our patients had complicated pregnancies: 26.1% had SLE flares, 13.9% had pre-eclampsia and 45.1% needed caesarean sections. There were 23.3% foetal losses and 25% preterm deliveries in our patients. There was a higher rate of unplanned pregnancies and lupus flare among pregnancies with active SLE at conception. Pregnancies in lupus nephritis have higher incidence of lupus flares during pregnancy but similar maternal and foetal outcomes compared to those without nephritis. The prognostic indicators for adverse foetal outcome in our patients were flare of SLE (HR 4.08 [CI 95% 1.65-10.13, p < 0.01]) and APS (HR 3.07 [CI 95% 1.12-8.42, p < 0.05]) and the prognostic indicator for adverse maternal outcome was hypertension (HR 3.58 [CI 95% 1.30-9.90, p < 0.05]). Lupus pregnancies in our centre remained as high-risk pregnancies with significant maternal and foetal complications.

A profile of gout patients in Sarawak.

We performed a prospective study of all patients diagnosed with gout and who received treatment in Sarawak General Hospital from 1 July 2010 to 31 December 2010. There was a total of 138 patients in our study of which 92 (66.7%) were from the indigenous populations. They have a mean age of 56.5 ± 12.5 years with a mean duration of illness of 11.6 ± 8.7 years. The mean lag time between symptom onset to the diagnosis of gout was 2.8 ± 4.8 years and a mean lag time to appropriate treatment of gout of 8.8 ± 8.4 years. Sixty-six (47.8%) patients have family history of gout. The common complications of gout in our patients were tophi (47.1%), joint deformities (39.1%), kidney stones (16.7%), and uric acid nephropathy (0.7%). Hospitalization occurred in 93 (67.4%) patients. Gout is a serious medical problem in our centre. Gout affects middle-aged men, especially the indigenous populations. Almost half of our patients have a family history of gout and have tophi formations. Our gout patients have a significant delay in diagnosis and appropriate treatment, thus contributing to more complications and hospitalizations in our centre. There is an urgent need to educate both patients and healthcare workers on gout and its treatment to reduce the burden of chronic gout in Sarawak.

A rare cause of back pain and radiculopathy - spinal tophi: a case report.

BACKGROUND: Gout is a monosodium urate deposition disease which is prevalent worldwide. The usual manifestations are crystal arthropathy and tophi deposition in the soft tissues. Spinal tophi may also occur and are rarely reported, resulting in various clinical manifestations such as back pain, spinal cord compression, radiculopathy, and even mimicking epidural abscess and spondylodiscitis. CASE PRESENTATION: We report a case of a 42-year-old Chinese man with underlying gout who presented with back pain and radiculopathy. The diagnosis of spinal tophi was unsuspected and he was initially treated for epidural abscess and spondylodiscitis. He underwent a laminectomy and posterolateral fusion during which tophus material was discovered. He recovered and medications for gout were started. CONCLUSION: Spinal tophi are rare. The diagnosis is difficult and spinal tophi may be mistaken for epidural abscess, spondylodiscitis, or neoplasm.

Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations.

Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.

Gyrospun antimicrobial nanoparticle loaded fibrous polymeric filters.

A one step approach to prepare hybrid nanoparticle embedded polymer fibres using pressurised gyration is presented. Two types of novel antimicrobial nanoparticles and poly(methylmethacrylate) polymer were used in this work. X-ray diffraction analysis of the nanoparticles revealed Ag, Cu and W are the main elements present in them. The concentration of the polymer solution and the nanoparticle concentration had a significant influence on the fibre diameter, pore size and morphology. Fibres with a diameter in the range of 6-20µm were spun using 20wt% polymer solutions containing 0.1, 0.25 and 0.5 wt% nanoparticles under 0.3MPa working pressure and a rotational speed of 36,000rpm. Continuous, bead-free fibre morphologies were obtained for each case. The pore size in the fibres varied between 36 and 300nm. Successful incorporation of the nanoparticles in polymer fibres was confirmed by energy dispersive x-ray analysis. The fibres were also gyrospun on to metallic discs to prepare filters which were tested for their antibacterial activity on a suspension of Pseudomonas aeruginosa. Nanoparticle loaded fibres showed higher antibacterial efficacy than pure poly(methylmethacrylate) fibres.

Piceatannol, a natural hydroxylated analog of resveratrol, promotes nitric oxide release through phosphorylation of endothelial nitric oxide synthase in human endothelial cells.

OBJECTIVE: Endothelial dysfunction associated with many cardiovascular diseases is largely due to reduced nitric oxide (NO) derived from endothelial NO synthase (eNOS). Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; Pic) is reported to have cardiovascular therapeutic effects. However, the cellular and molecular mechanisms underlying the cardioprotective effects of Pic are still unclear. Here, we investigated whether Pic could influence endothelial NO release in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: In HUVECs exposed to Pic, NO production and phosphorylation of eNOS and protein kinase B (Akt) were determined by using a commercially available NO assay kit and Western blot analysis, respectively. RESULTS: Pic stimulated dose- and time-dependent NO production via eNOS phosphorylation. Pic also stimulated dose-dependent phosphorylation of Akt. Interestingly, NO production and eNOS phosphorylation in response to Pic were significantly abolished by the phosphoinositide 3-kinase (PI3K)/Akt inhibitor LY294002. CONCLUSIONS: Pic is capable of inducing eNOS phosphorylation and the subsequent NO release, presumably, by activating PI3K/Akt pathway. The potential efficacy of Pic, a natural hydroxylated analog and a metabolite of resveratrol, may aid in the prevention of cardiovascular diseases characterized by endothelial dysfunction.

Comparison of intensity-dependent inhibition of spinal wide-dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain.

BACKGROUND: Spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are thought to reduce pain by activating a sufficient number of large myelinated (Aß) fibres, which in turn initiate spinal segmental mechanisms of analgesia. However, the volume of neuronal activity and how this activity is associated with different treatment targets is unclear under neuropathic pain conditions. METHODS: We sought to delineate the intensity-dependent mechanisms of SCS and PNS analgesia by in vivo extracellular recordings from spinal wide-dynamic range neurons in nerve-injured rats. To mimic therapeutic SCS and PNS, we used bipolar needle electrodes and platinum hook electrodes to stimulate the dorsal column and the tibial nerve, respectively. Compound action potentials were recorded to calibrate the amplitude of conditioning stimulation required to activate A-fibres and thus titrate the volume of activation. RESULTS: Dorsal column stimulation (50 Hz, five intensities) inhibited the windup (a short form of neuronal sensitization) and the C-component response of wide-dynamic range neurons to graded intracutaneous electrical stimuli in an intensity-dependent manner. Tibial nerve stimulation (50 Hz, three intensities) also suppressed the windup in an intensity-dependent fashion but did not affect the acute C-component response. CONCLUSIONS: SCS and PNS may offer similar inhibition of short-term neuronal sensitization. However, only SCS attenuates spinal transmission of acute noxious inputs under neuropathic pain conditions. Our findings begin to differentiate peripheral from spinal-targeted neuromodulation therapies and may help to select the best stimulation target and optimum therapeutic intensity for pain treatment.

Note: Fabrication of tapered fibre tip using mechanical polishing method.

Tapered fibre tips fabricated using mechanical polishing method is studied. The fibre tips are formed by sequential polishing flat-ended single mode fibres with decreasing aluminium oxide polishing film grit size. Based on the proposed technique, tapered fibre tips with cone angle ranging from 30° to 130° are fabricated by controlling the polishing angle. Besides the variety of cone angle, considerable smoothness of the fibre tip surface may assist in good metal coating and hence a well-defined aperture can be obtained. In addition, this paper presents a two-step hybrid fabrication method combining the proposed polishing method with chemical etching method to increase the possible fibre tip cone angles achievable by chemical etching method.