ABSTRACT
In advanced cancer, pain is a poor prognostic factor, significantly impacting patients' quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations.
ABSTRACT
Acute pharyngitis (AP) is a common reason for private primary care consultations, thus providing an avenue for widespread antibiotic intake among the community. However, there is limited data on the antibiotic prescription appropriateness and resistance information in the Malaysian private primary care setting, therefore, this study aimed to investigate the prevalence of isolated viruses and bacteria, antibiotic resistance patterns, antibiotic prescription patterns and appropriateness by general practitioners (GPs) and factors affecting antibiotic resistance and antibiotic prescription patterns. To investigate, a cross-sectional study was conducted among 205 patients presenting with AP symptoms at private primary care clinics in central Malaysia from 3rd January 2016 to 30th November 2016. Throat swabs were collected from 205 AP patients for two purposes: (i) the detection of four common respiratory viruses associated with AP via reverse-transcription real-time PCR (qRT-PCR); and (ii) bacterial identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Bacterial isolates were then subjected to antibiotic susceptibility screening and McIsaac scoring was calculated post-prescription based on GP selection of criteria. Generalized estimating equations analysis with multiple logistic regression was conducted to identify factors associated with presence of virus and antibiotic prescription. The results showed that 95.1% (195/205) of patients had at least one of the four viruses, with rhinovirus (88.5%) being the most prevalent, followed by adenovirus (74.9%), influenza A virus (4.6%) and enterovirus (2.1%). A total of 862 non-repetitive colonies were isolated from the culture of throat swabs from 205 patients who were positive for bacteria. From a total of 22 genera, Streptococcus constitutes the most prevalent bacteria genus (40.9%), followed by Neisseria (20%), Rothia (13.0%), Staphylococcus (11%) and Klebsiella (4.9%). Only 5 patients carried group A beta-hemolytic streptococci (GABHS). We also report the presence of vancomycin-resistant S. aureus or VRSA (n = 9, 10.1%) among which one isolate is a multidrug-resistant methicillin-resistant S. aureus (MDR-MRSA), while 54.1% (n = 111) were found to carry at least one antibiotic-resistant bacteria species. Application of the McIsaac scoring system indicated that 87.8% (n = 180) of patients should not be prescribed antibiotics as the majority of AP patients in this study had viral pharyngitis. The antibiotic prescription appropriateness by applying post-prescription McIsaac scoring was able to rule out GABHS pharyngitis in this sample with a GABHS culture-positive sensitivity of 40% (n = 2/5) and specificity of 90% (180/200). In conclusion, antibiotic-resistant throat isolates and over-prescription of antibiotics were observed and McIsaac scoring system is effective in guiding GPs to determine occurrences of viral pharyngitis to reduce unnecessary antibiotic prescription.