Second nationwide anti-tuberculosis drug resistance survey in Namibia.

SETTING: Namibia ranks among the 30 high TB burden countries worldwide. Here, we report results of the second nationwide anti-TB drug resistance survey.OBJECTIVE: To assess the prevalence and trends of multidrug-resistant TB (MDR-TB) in Namibia.METHODS: From 2014 to 2015, patients with presumptive TB in all regions of Namibia had sputum subjected to mycobacterial culture and phenotypic drug susceptibility testing (DST) for rifampicin, isoniazid, ethambutol and streptomycin if positive on smear microscopy and/or Xpert MTB/RIF.RESULTS: Of the 4124 eligible for culture, 3279 (79.5%) had Mycobacterium tuberculosis isolated. 3126 (95%) had a first-line DST completed (2392 new patients, 699 previously treated patients, 35 with unknown treatment history). MDR-TB was detected in 4.5% (95%CI 3.7-5.4) of new patients, and 7.9% (95%CI 6.0-10.1) of individuals treated previously. MDR-TB was significantly associated with previous treatment (OR 1.8, 95%CI 1.3-2.5) but not with HIV infection, sex, age or other demographic factors. Prior treatment failure demonstrated the strongest association with MDR-TB (OR 17.6, 95%CI 5.3-58.7).CONCLUSION: The prevalence of MDR-TB among new TB patients in Namibia is high and, compared with the first drug resistance survey, has decreased significantly among those treated previously. Namibia should implement routine screening of drug resistance among all TB patients.

Oral health awareness and care preferences in patients with diabetes: a qualitative study.

BACKGROUND: People with type 2 diabetes have an increased risk of oral health problems; however, oral health is currently not included in structured diabetes reviews and education in the UK. AIM AND OBJECTIVES: This study explores the patient's experience related to oral health and diabetes, especially in relation to: • Awareness of the link between oral health and diabetes and oral self-care needs. • Interaction with health professionals in dental and general practice. • Preferences for receiving oral health information and education. Methods This nested qualitative study involved semi-structured telephone interviews with a purposive sample of 20 participants from a questionnaire study on oral health awareness in patients with diabetes. Interview transcripts were analysed using a thematic framework approach. RESULTS: Participants were mostly unaware of the link between oral health and diabetes. Those that had been made aware by a health professional were not given concrete self-care advice. Interactions with dental professionals were often limited to informing the dental practice of their diagnosis and current medication. Most participants were in favour of dentists screening for diabetes, but as their general practice was the hub for diabetes care, they felt GPs or nurses should provide oral health information and discuss oral health with patients. CONCLUSIONS: Written information regarding diabetes and its possible effects on oral health needs to be more readily available to people with diabetes, especially at diagnosis. There may be a place for introducing a structured oral health question in routine diabetes reviews.

First Report of Soybean Rust Caused by Phakopsora pachyrhizi on Pachyrhizus erosus in the United States.

Soybean rust, caused by the fungus Phakopsora pachyrhizi, was detected on jicama (Pachyrhizus erosus L. Urban) for the first time in the United States in November 2009. The pathogen was observed on leaves of a single, potted jicama plant grown outdoors in a residential area and on leaves of all plants in a 12-m2 demonstration plot located at the Auburn University Teaching Garden in Auburn, AL. Symptoms on the upper leaf surfaces were isolated chlorotic areas near the leaf edges in the lower part of the canopy. The abaxial surface was first observed to exhibit brown lesions and subsequently produced volcano-shaped uredinia. These symptoms are consistent with a rust previously described on jicama in Mexico (1). Representative symptomatic plant tissue was sent to the USDA National Identification Services (Mycology) Laboratory in Beltsville, MD for diagnostic confirmation at both the Urbana, IL lab and the USDA National Plant Germplasm and Biotechnology Laboratory for DNA testing. From an infected leaf, samples of approximately 5 mm2 were excised from a microscopically observed rust lesion and an apparently noninfected area. Total DNA was purified with the FastDNA Spin Kit (MP Biomedicals, Solon, OH) followed by the E.Z.N.A. MicroElute DNA Clean-Up Kit (Omega Bio-tek, Inc, Doraville, GA) per manufacturer's instructions. Detection of P. pachyrhizi and P. meibomiae DNA was achieved by quantitative PCR using the method of Frederick et al. (2) and a DNA standard of previously prepared P. pachyrhizi spores. The observed rust pustule was found to contain P. pachyrhizi DNA in excess of 28,000 genomes, while no P. pachyrhizi DNA was observed from the asymptomatic sample. Both samples were negative for P. meibomiae. The fungal structures present were confirmed to be Phakopsora spp. DNA was extracted from sori aseptically removed from leaves with a Qiagen (Valencia, CA) DNeasy Plant Mini Kit and amplified with primers Ppa1 and NL4. The resulting partial ITS2 and 28S ribosomal RNA sequences were 100% identical to GenBank entry DQ354537 P. pachyrhizi internal transcribed spacer 2 and 28S ribosomal RNA gene, partial sequence. Sequences from jicama from Alabama were deposited in GenBank. Voucher specimens were deposited in the USDA Agricultural Research Service, National Fungus Collection (BPI). To our knowledge, this is the first report of the disease on jicama in the United States. References: (1) A. Cárcamo Rodriguez et al. Plant Dis. 90:1260, 2006. (2) R. D. Frederick et al. Phytopathology 92:217, 2002.

Treatment of hyper-IgG4 disease with sequential corticosteroids and tamoxifen - case report and review of the literature.

We report a patient with multifocal fibrosclerosis presenting as sialadenitis, hepatic fibrosis, and retroperitoneal fibrosis with renal failure. His medical management consisted of prednisone (4 months at 40 mg daily, then tapered down to 5 mg daily for another 14 months) and 18 months of tamoxifen. He responded clinically and radiographically to this regimen, and remains in clinical remission 10 months after discontinuing medical therapy. Subsequent histologic examination of submandibular gland tissue revealed strong staining for IgG4-positive plasma cells. To our knowledge, this is the first case of confirmed multifocal hyper-IgG4 disease to be successfully treated with sequential corticosteroids and tamoxifen.

Snapback primer genotyping with saturating DNA dye and melting analysis.

BACKGROUND: DNA hairpins have been used in molecular analysis of PCR products as self-probing amplicons. Either physical separation or fluorescent oligonucleotides with covalent modifications were previously necessary. METHODS: We performed asymmetric PCR for 40-45 cycles in the presence of the saturating DNA dye, LCGreen Plus, with 1 primer including a 5' tail complementary to its extension product, but without any special covalent modifications. Samples were amplified either on a carousel LightCycler for speed or on a 96/384 block cycler for throughput. In addition to full-length amplicon duplexes, single-stranded hairpins were formed by the primer tail "snapping back" and hybridizing to its extension product. High-resolution melting was performed on a HR-1 (for capillaries) or a LightScanner (for plates). RESULTS: PCR products amplified with a snapback primer showed both hairpin melting at lower temperature and full-length amplicon melting at higher temperature. The hairpin melting temperature was linearly related to the stem length (6-28 bp) and inversely related to the log of the loop size (17-135 bases). We easily genotyped heterozygous and homozygous variants within the stem, and 100 blinded clinical samples previously typed for F5 1691G>A (Leiden) were completely concordant by snapback genotyping. We distinguished 7 genotypes in 2 regions of CFTR exon 10 with symmetric PCR using 2 snapback primers followed by product dilution to favor intramolecular hybridization. CONCLUSIONS: Snapback primer genotyping with saturating dyes provides the specificity of a probe with only 2 primers that are free of special covalent labels in a closed-tube system.

The Toronto Western Hospital catheter: one center's experience and review of the literature.

BACKGROUND: We report our center's experience with the Toronto Western Hospital (TWH) catheter, and discuss our catheter survival and complication rates. METHODS: Retrospective chart review of patients receiving peritoneal dialysis therapy via a TWH catheter. Catheter complication rates of peritonitis, exit site infection, obstruction, leak, and malfunction were assessed. A catheter was considered failed if removed because of exit site infection, obstruction, or malfunction. All other catheters, even if removed for other reasons, were considered censured. Survival was defined as the period from insertion to failure or censure date, and reported using Kaplan Meier analysis. RESULTS: 192 patients with a total of 208 TWH catheters (4,845.3 catheter months) were analyzed. Our overall 1- and 3-year catheter survival rates were identical at 0.9182. Our catheter complication rates (expressed as number of catheter months per event) were 31.3 for peritonitis, 42.9 for exit site infection, 72.3 for obstruction, 538.4 for malfunction, and 969.1 for catheter leak. Our findings were similar to those reported in the literature for TWH and other peritoneal catheters.

Symptom interval in young people with bone cancer.

Symptom interval (SI), the time from first symptom/sign to diagnosis and initiation of treatment, appears to be principally influenced by tumour biology. Whether the age of the patient, patient delay, professional delay and access to health professionals influences the SI in bone tumours was investigated in this study. 115 patients with newly diagnosed osteosarcoma and Ewing's sarcoma were retrospectively reviewed. The median total SI for all bone tumours was 3.8 months (range 1-46 months). Patients older than 12 years had a longer SI (P = 0.05) and more patient delays (P = 0.02). Total SI and professional delays were longer if the General Practitioner was first seen compared with an Accident and Emergency Consultant (P = 0.02 and 0.02, respectively). However, SI did not influence overall and event-free survival in this series. Bone tumour patients have long SIs that are significantly affected by age and local health-care support systems. Early referral to specialists would help to alleviate anxiety and distress to the patient and family, even if currently delay does not influence outcome.

Chronic peritoneal dialysis in octogenarians.

BACKGROUND: During the past few decades the pattern of end-stage renal failure disease has changed with increasing number of elderly patients admitted for dialysis. In spite of their increasing number, little is known about the optimal mode of therapy of the 'old old' (those >or=80 years) patients. METHODS: In this retrospective study, we analysed the results of treatment of 31 non-institutionalized 'old old' patients at Toronto Western Hospital (17) and Scarborough General Hospital (14) and seven institutionalized patients in chronic care, Riverdale Hospital. The patients were on CAPD with Twin-bag Baxter (28) or Home Choice, Baxter or Fresenius CCPD system (10). Patients were screened at the CAPD clinic when routine blood investigations were done. Patient and technique survival, initial and final laboratory data (last visit or before death) and complications related/unrelated to dialysis method are presented. RESULTS: Multiple comorbid conditions were present at the start of the treatment and new added during treatment; very few were dialysis-related. The majority of non-institutionalized patients required assistance of home-care nurse to perform dialysis. Peritonitis (1/28.6 patient months) and exit-site infection rate (1/75.1 patient months) were low and responded to treatment. Incidence of peritonitis was higher among institutionalized debilitated patients (1/5.3 patient months). Incidence of hospitalization was 1/14.7 patient months and patients spent in hospital 7.5 days/patient year. Forty-seven per cent of patients survived 24 months; 39% survived 30 months. Technique survival was 91.5% at 12 months and 81.4% at 30 months. Poor appetite and malnutrition were frequent among very old patients. Patients and their families were motivated for treatment and discontinuation of dialysis was not higher than described elsewhere in literature. CONCLUSIONS: This study has demonstrated that chronic peritoneal dialysis could be recommended as a safe and suitable modality of treatment of end-stage renal failure in old old patients.

The role of patients' expectations in the development of anticipatory nausea related to chemotherapy for cancer.

Although anticipatory nausea (AN), which is reported by one-third of patients receiving chemotherapy for cancer, is thought to develop primarily by classical conditioning, response expectancies may also be important. The role of patients' expectations of nausea in the development of AN was examined in 63 female cancer patients receiving their first course of chemotherapy. Twenty women (32%) expected to experience nausea and twelve (19%) reported AN before the third cycle. Pretreatment expectations predicted AN at cycle three (Spearman's r = 0.41, P = 0.001). AN developed in 40% of patients who expected nausea, 13% of those who were uncertain whether they would develop it, and no patients who did not expect nausea. Logistic regression indicated that expecting nausea was the strongest predictor (chi(2) =13.15; P < 0.001). Results support a role for cognitive factors in the development of chemotherapy side effects and suggest testing psychologic interventions to modify patients' expectations.

The design of phenylglycine containing benzamidine carboxamides as potent and selective inhibitors of factor Xa.

Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa.

Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices.

Data from 1413 outpatients in community-based clinical practices were collected in order to characterize the use and effectiveness of 5-HT(3) receptor antagonists for control of chemotherapy-induced nausea and vomiting (NV). Patients were divided by treatment starting date into six cohorts for trend analysis. In addition, NV symptoms were compared in 252 patients treated prior to the commercial introduction of the 5-HT(3) receptor antagonist antiemetics, and an equal number of patients treated after their introduction. A comparison of cohorts revealed a significant (P = 0. 027) downward trend over time for the frequency of post-treatment vomiting episodes, but not for frequency of post-treatment nausea (P = 0.69). The average duration of nausea following treatment increased significantly over time (P = 0.003). Although the introduction of 5-HT(3) receptor antagonist antiemetics has apparently led to a significant reduction in the frequency of post-treatment vomiting, there has been an accompanying increase in the duration of post-treatment nausea.

Patient expectations as predictor of chemotherapy-induced nausea.

We examined the relationship between patients' pretreatment expectations for nausea and vomiting and their subsequent development in a homogeneous group of 29 female cancer patients receiving platinum-containing chemotherapy as inpatients (Study 1) and in 81 subjects with any of a variety of cancer diagnoses treated largely as outpatients (Study 2). Each study found a significant relationship between patients' expectations for nausea development measured prior to their first treatment and their mean postchemotherapy nausea severity (both, p < 0.05). Patients' expectations accounted for unique variance in nausea severity in each study even after controlling for known pharmacological and physiological predictors of nausea (Study 1: delta R2 = .18, p < .04; Study 2: delta R2 = .05, p < .03). By contrast, we found no significant relationships between expectations for vomiting and subsequent vomiting. Our results support the view that patients' expectations for nausea affect its subsequent development, indicating the presence of a significant psychological component in treatment-related nausea. Implications of this are discussed.

Sources of information used by patients to learn about chemotherapy side effects.

BACKGROUND: Little is known about the relative importance of specific information sources patients use to obtain knowledge about treatment side effects. The authors examined information sources used to learn about side effects, why patients believe they will experience some but not others, and the meanings side effects have in terms of treatment efficacy. METHODS: Before treatment, 31 ovarian cancer patients and 81 men and women with a variety of cancer diagnoses completed a questionnaire assessing their expectations about experiencing specific side effects of chemotherapy and information sources used. RESULTS: The doctor or nurse was the most frequently cited source of side-effect information, with readings second. While most thought they would get certain side effects because the doctor or nurse had said so, most instinctively believed they would not get others. CONCLUSIONS: Patients relied on medical and non-medical information sources. Further research could examine other sources for their influences on information-seeking activities.

Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes.

Malignant gliomas exhibit alkaline intracellular pH (pH(i)) and acidic extracellular pH (pH(e)) compared with nontransformed astrocytes, despite increased metabolic H(+) production. The acidic pH(e) limits the availability of HCO(-)(3), thereby reducing both passive and dynamic HCO(-)(3)-dependent buffering. This implies that gliomas are dependent upon dynamic HCO(-)(3)-independent H(+) buffering pathways such as the type 1 Na(+)/H(+) exchanger (NHE1). In this study, four rapidly proliferating gliomas exhibited significantly more alkaline steady-state pH(i) (pH(i) = 7.31-7.48) than normal astrocytes (pH(i) = 6.98), and increased rates of recovery from acidification, under nominally CO(2)/HCO(-)(3)-free conditions. Inhibition of NHE1 in the absence of CO(2)/HCO(-)(3) resulted in pronounced acidification of gliomas, whereas normal astrocytes were unaffected. When suspended in CO(2)/HCO(-)(3) medium astrocyte pH(i) increased, yet glioma pH(i) unexpectedly acidified, suggesting the presence of an HCO(-)(3)-dependent acid loading pathway. Nucleotide sequencing of NHE1 cDNA from the gliomas demonstrated that genetic alterations were not responsible for this altered NHE1 function. The data suggest that NHE1 activity is significantly elevated in gliomas and may provide a useful target for the development of tumor-selective therapies.

Venous stenosis and thrombosis associated with the use of internal jugular vein catheters for hemodialysis.

Previous studies have demonstrated venous stenosis and thrombosis in hemodialysis patients who had repeated or prolonged cannulation of the subclavian vein. Early reports, however suggested that patients with catheters placed in the internal jugular vein were not at risk of such complications. We conducted a retrospective case series to determine if this was correct. We report a series of seven patients who were found to have stenosis of the upper neck veins despite having never had subclavian vein cannulation. We suggest that previous reports suggesting a superior safety profile with internal jugular catheters may have been misleading and propose that all measures be taken to encourage wider use of arteriovenous grafts and fistulae.

Use of 5-HT3 receptor antagonists to prevent nausea and emesis caused by chemotherapy for patients with breast carcinoma in community practice settings.

BACKGROUND: Although 5-HT3 receptor antagonists are clinically more effective in controlling emesis, particularly that caused by high dose cisplatin, than previously available agents, they appear to be less effective against nausea. This report focuses on the effectiveness of these agents against nausea and emesis in patients receiving two moderately emetogenic combination chemotherapy regimens as treatment for breast carcinoma in community practice settings. METHODS: Six hundred ninety-two breast carcinoma patients (688 female, 4 male; mean age, 51 years) enrolled in a nonrandomized study completed the Morrow Assessment of Nausea and Emesis (MANE) following 4 consecutive chemotherapy treatments. The frequency, duration, and severity of postchemotherapy nausea (PN) and postchemotherapy emesis (PE) were compared by type of antiemetic (5-HT3 receptor antagonist vs. other) and chemotherapy regimen (cyclophosphamide and doxorubicin with or without 5-fluorouracil [CA/CAF] vs. cyclophosphamide, methrotrexate, and 5-fluorouracil [CMF]). RESULTS: Within each regimen, the mean duration of PN was significantly longer for patients who received a 5-HT3 receptor antagonist than for those who were not given an antiemetic of that type (CA: 40.3 hours vs. 29.6 hours, P < 0.05; CMF: 37.6 hours vs. 30.2 hours, P < 0.05). There were no significant differences in the frequency or severity of nausea or in the frequency, severity, or duration of emesis by type of antiemetic for patients receiving either regimen. CONCLUSIONS: The results of this observational study suggest that 5-HT3 receptor antagonists are no more effective than other commonly used medications in controlling postchemotherapy nausea and emesis in women with breast carcinoma who are treated with moderately emetogenic chemotherapy in community practice settings. In fact, they may be associated with significant prolongation of the course of postchemotherapy nausea.

Is peritoneal dialysis a good option for black patients?

Blacks are less likely than whites to use peritoneal dialysis (PD) as the initial renal replacement therapy. The reason for the underusage of PD by blacks is unknown. In a cross-sectional multicenter trial, we studied peritoneal transport character, small-molecular-weight solute clearances, and nutritional status in 475 patients undergoing PD (168 whites, 192 blacks, and 115 Asians). The mean age of blacks undergoing PD was significantly younger than that of whites (47.6 +/- 14.7 v 58.2 +/- 16.7 years; P < 0.0001). Target Kt/V and weekly creatinine clearance (WCC) as defined by the Dialysis Outcome Quality Initiative Work Group was achieved by 62.5% of whites, 67.2% of blacks, and 54.8% of Asians (P = 0.05). Total protein (7.25 +/- 0.88 v 6.55 +/- 0.73 g/dL), albumin (3.72 +/- 0.57 v 3.55 +/- 0.53 g/dL), and lean body mass (LBM; 41.7 +/- 15.6 v 33.0 +/- 11.8 kg) were lower in whites compared with blacks (P < 0.001). Although the normalized protein catabolic rate (nPCR) was greater (0.82 +/- 0.24 v 0.90 +/- 0.32 g/kg/d; P = 0.04), total protein (6.24 +/- 0.85 g/dL) and serum albumin levels (3.36 +/- 0.52 g/dL) and LBM (30.1 +/- 8.0 kg) were significantly lower in Asians than blacks (P < 0.0001). The favorable anabolic response in blacks may partially be explained by a higher calorie intake in this group of patients (29.6 +/- 10.7 Cal/kg/d) compared with whites (22.4 +/- 6.8 Cal/kg/d) and Asians (23.9 +/- 9.8 Cal/kg/d; P = 0.03). Multiple regression analysis identified that black race and weight were positively associated, whereas dialysate/plasma creatinine ratio (D/P(Creat)) and age had a negative effect on serum albumin level. Follow-up data indicated that the Kt/V (2.09 +/- 0.50 v 2.39 +/- 0.56; P = 0.02) and WCC (60.8 +/- 4.3 v 70.2 +/- 7.3 L/1.73 m2; P = 0.02) increased significantly from baseline only in blacks. We conclude that PD is an ideal renal replacement therapy in at least a subset of blacks with end-stage renal disease.