First imported Cases of MPXV Clade Ib in Goma, Democratic Republic of the Congo: Implications for Global Surveillance and Transmission Dynamics.

The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years.

Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo.

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.

Genetic diversity of glutamate-rich protein (GLURP) in Plasmodium falciparum isolates from school-age children in Kinshasa, DRC.

Malaria infections in school-age children further make it difficult to control the disease's spread. Moreover, the genetic diversity of glutamate-rich protein, potentially a candidate for vaccine development, has not yet been investigated in the Democratic Republic of Congo. Therefore, we aimed to assess the genetic diversity of the immunodominant C-terminal repetitive region (R2) of Plasmodium falciparum glutamate-rich protein gene (pfglurp) among school-age children living in Kinshasa, DRC. We conducted nested PCR targeting R2 of pfglurp and the amplicon were directly sequenced. We summarized the prevalence of mutations of bases and amino acids and indicated the amino acid repeat sequence in the R2 region by the unit code. We then statistically analyzed whether there was a relationship between the number of mutations in the pfglurp gene and attributes. In 221 samples, haplotype 1 was the most common (n = 137, 61.99%), with the same sequence as the 3D7 strain. Regarding the number of base mutations, it was higher in urban areas than rural areas (p = 0.0363). When genetic neutrality was tested using data from 171 samples of the single strain, Tajima's D was -1.857 (p = 0.0059). In addition, FST as the genetic distance between all attributes was very small and no significant difference was observed. This study clarified the genetic mutation status and relevant patient attributes among School-age children in the DRC. We found that urban areas are more likely to harbour pfglurp mutations. Future research needs to clarify the reason and mechanism involved.

The diversity of Plasmodium falciparum isolates from asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo.

BACKGROUND: Understanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC). METHODS: A total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3. RESULTS: Nine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001). CONCLUSION: This survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC.

It Is Time to Strengthen the Malaria Control Policy of the Democratic Republic of Congo and Include Schools and School-Age Children in Malaria Control Measures.

Despite a decade of sustained malaria control, malaria remains a serious public health problem in the Democratic Republic of Congo (DRC). Children under five years of age and school-age children aged 5-15 years remain at high risk of symptomatic and asymptomatic malaria infections. The World Health Organization's malaria control, elimination, and eradication recommendations are still only partially implemented in DRC. For better malaria control and eventual elimination, the integration of all individuals into the national malaria control programme will strengthen malaria control and elimination strategies in the country. Thus, inclusion of schools and school-age children in DRC malaria control interventions is needed.

Low prevalence of Plasmodium falciparum parasites lacking pfhrp2/3 genes among asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.

BACKGROUND: Loss of efficacy of diagnostic tests may lead to untreated or mistreated malaria cases, compromising case management and control. There is an increasing reliance on rapid diagnostic tests (RDTs) for malaria diagnosis, with the most widely used of these targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). There are numerous reports of the deletion of this gene in P. falciparum parasites in some populations, rendering them undetectable by PfHRP2 RDTs. The aim of this study was to identify P. falciparum parasites lacking the P. falciparum histidine rich protein 2 and 3 genes (pfhrp2/3) isolated from asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo. METHODS: The performance of PfHRP2-based RDTs in comparison to microscopy and PCR was assessed using blood samples collected and spotted on Whatman 903™ filter papers between October and November 2019 from school-age children aged 6-14 years. PCR was then used to identify parasite isolates lacking pfhrp2/3 genes. RESULTS: Among asymptomatic malaria carriers (N = 266), 49%, 65%, and 70% were microscopy, PfHRP2_RDT, and pfldh-qPCR positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 80% and 70% while the sensitivity and specificity of RDTs compared to microscopy were 92% and 60%, respectively. Among symptomatic malaria carriers (N = 196), 62%, 67%, and 87% were microscopy, PfHRP2-based RDT, pfldh-qPCR and positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 75% and 88%, whereas the sensitivity and specificity of RDTs compared to microscopy were 93% and 77%, respectively. Of 173 samples with sufficient DNA for PCR amplification of pfhrp2/3, deletions of pfhrp2 and pfhrp3 were identified in 2% and 1%, respectively. Three (4%) of samples harboured deletions of the pfhrp2 gene in asymptomatic parasite carriers and one (1%) isolate lacked the pfhrp3 gene among symptomatic parasite carriers in the RDT positive subgroup. No parasites lacking the pfhrp2/3 genes were found in the RDT negative subgroup. CONCLUSION: Plasmodium falciparum histidine-rich protein 2/3 gene deletions are uncommon in the surveyed population, and do not result in diagnostic failure. The use of rigorous PCR methods to identify pfhrp2/3 gene deletions is encouraged in order to minimize the overestimation of their prevalence.

Identification of polymorphisms in genes associated with drug resistance in Plasmodium falciparum isolates from school-age children in Kinshasa, Democratic Republic of Congo.

BACKGROUND: The emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs constitutes an obstacle to malaria control and elimination. This study aimed to identify the prevalence of polymorphisms in pfk13, pfmdr1, pfdhfr, pfdhps and pfcrt genes in isolates from asymptomatic and symptomatic school-age children in Kinshasa. METHODS: Nested-PCR followed by sequencing was performed for the detection of pfk13, pfmdr1, pfdhfr, pfdhps and pfcrt polymorphisms. RESULTS: Two mutations in pfk13, C532S and Q613E were identified in the Democratic Republic of Congo for the first time. The prevalence of the drug-resistance associated mutations pfcrt K76T, pfdhps K540E and pfmdr1 N86Y was low, being 27%, 20% and 9%, respectively. CONCLUSION: We found a low prevalence of genetic markers associated with chloroquine and sulfadoxine-pyrimethamine resistance in Kinshasa. Furthermore, no mutations previously associated with resistance against artemisinin and its derivatives were observed in the pfK13 gene. These findings support the continued use of ACTs and IPTp-SP. Continuous molecular monitoring of antimalarial resistance markers is recommended.

Malaria parasite species composition of Plasmodium infections among asymptomatic and symptomatic school-age children in rural and urban areas of Kinshasa, Democratic Republic of Congo.

BACKGROUND: Malaria remains a major public health concern in the Democratic Republic of Congo (DRC), and school-age children are relatively neglected in malaria prevalence surveys and may constitute a significant reservoir of transmission. This study aimed to understand the burden of malaria infections in school-age children in Kinshasa/DRC. METHODS: A total of 634 (427 asymptomatic and 207 symptomatic) blood samples collected from school-age children aged 6 to 14 years were analysed by microscopy, RDT and Nested-PCR. RESULTS: The overall prevalence of Plasmodium spp. by microscopy, RDT and PCR was 33%, 42% and 62% among asymptomatic children and 59%, 64% and 95% in symptomatic children, respectively. The prevalence of Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale spp. by PCR was 58%, 20% and 11% among asymptomatic and 93%, 13% and 16% in symptomatic children, respectively. Among P. ovale spp., P. ovale curtisi, P. ovale wallikeri and mixed P. ovale curtisi + P. ovale wallikeri accounted for 75%, 24% and 1% of infections, respectively. All Plasmodium species infections were significantly more prevalent in the rural area compared to the urban area in asymptomatic infections (p < 0.001). Living in a rural as opposed to an urban area was associated with a five-fold greater risk of asymptomatic malaria parasite carriage (p < 0.001). Amongst asymptomatic malaria parasite carriers, 43% and 16% of children harboured mixed Plasmodium with P. falciparum infections in the rural and the urban areas, respectively, whereas in symptomatic malaria infections, it was 22% and 26%, respectively. Few children carried single infections of P. malariae (2.2%) and P. ovale spp. (1.9%). CONCLUSION: School-age children are at significant risk from both asymptomatic and symptomatic malaria infections. Continuous systematic screening and treatment of school-age children in high-transmission settings is needed.

Right aortic arch with mirror image branching found incidentally during coronary surgery.

Right aortic arch with a left innominate (brachiocephalic) artery with mirror image branching (RAMI) is a rare congenital anomaly, and it is unusual to diagnose it in adulthood. There are very few cases of cardiac surgery being performed for acquired cardiac disease on a congenital RAMI patient. We present a patient who had an incidental finding of a RAMI anomaly found during coronary artery bypass surgery. Post-operatively computerised tomography showed both his congenital lesions and his bypass grafts.

Pharmacokinetic changes of psychotropic drugs in patients with liver disease: implications for dose adaptation.

Dose adjustment of psychotropic drugs in patients with liver cirrhosis may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. Psychotropic drugs (antiepileptics, antiparkinsonian drugs, psycholeptics such as antipsychotics, anxiolytics, sedatives and hypnosedatives, and psychoanaleptics such as antidepressants, psychostimulants and antidementia drugs) marketed in Switzerland in 2006 were therefore classified according to their hepatic extraction and/or bioavailability to predict their kinetic behaviour in patients with cirrhosis. The expected changes in hepatic metabolism predicted by pharmacokinetic properties were compared with the results from kinetic studies carried out in patients with liver disease. These studies were identified using MEDLINE searches. Of the 116 psychotropic drugs available on the Swiss market by the year 2006, only 12 were predominantly eliminated through the kidney. For five substances, no Q(0) value (the dose fraction metabolized or excreted extra-renally) could be determined because of lack of pharmacokinetic data. Of 99 drugs with predominant hepatic metabolism, 29.3% were categorized as high, 25.2% as intermediate and 38.4% as low extraction drugs, while seven substances could not be classified. Pharmacokinetic studies in patients with liver disease were available for 55 of these 99 drugs eliminated predominantly by the liver (Q(0)-value > or = 0.5). Only a few kinetic studies in patients with liver disease were found for antipsychotics, antiparkinsonian drugs and antidepressants, except for selective serotonin reuptake inhibitors and some newer antidepressants. The expected changes in pharmacokinetics were generally in good agreement with the changes reported in pharmacokinetic studies. For 12 drugs, the observed changes in pharmacokinetics from clinical studies were different from the changes expected based on their classification. However, for low extraction drugs metabolized by cytochrome P450 isozymes, clearance may be reduced by up to 50%. In conclusion, the classification of drugs according to their hepatic extraction and/or bioavailability is a useful tool for dose adjustment, if information from clinical studies is lacking. There is a gap in information about pharmacokinetic changes in patients with liver cirrhosis for a large number of centrally acting drugs. Kinetic studies for centrally acting drugs with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.

Age-related differences in the prevalence of potential drug-drug interactions in ambulatory dyslipidaemic patients treated with statins.

BACKGROUND AND OBJECTIVE: Elderly patients may be at higher risk of drug-drug interactions (DDIs) because of polypharmacy. This study evaluated age-specific differences in the prevalence of clinically relevant potential DDIs (pDDIs) in ambulatory dyslipidaemic patients treated with an HMG-CoA reductase inhibitor (statin). We hypothesised that elderly patients are at higher risk for pDDIs because of the presence of more drugs and drugs with a higher potential for DDIs in this age group. METHODS: A total of 2742 dyslipidaemic ambulatory patients treated with a statin were included in this cross-sectional study. Drug treatment was screened for clinically relevant pDDIs using an electronic drug interaction program (DRUG-REAX System). RESULTS: The study sample consisted of 483 (17.6%) patients aged < or = 54 years, 732 (26.7%) aged 55-64 years, 924 (33.7%) aged 65-74 years and 603 (22.0%) patients aged > or = 75 years. Patients > or =75 years had significantly more pharmacologically active substances prescribed than patients aged < or =54 years (mean 5.8 vs 3.8, respectively; p < 0.001). Cardiovascular diseases such as coronary heart disease, heart failure or arrhythmias were also significantly more prevalent in patients aged > or = 75 years than in younger patients. The overall prevalence of pDDIs increased significantly from 7.9% in those aged < or = 54 years to 18.4% in patients aged > or = 75 years (p < 0.001). The frequency of both pDDIs associated with statins and non-statin pDDIs increased with age. Risk factors for pDDIs in patients aged > or = 75 years were arrhythmias, heart failure and the number of pharmacologically active substances prescribed. The more frequent prescription of cardiovascular drugs with a high potential for pDDIs (e.g. amiodarone and digoxin) in patients aged > or = 75 years was mainly responsible for the observed increases in statin and non-statin pDDIs in this age group. CONCLUSIONS: Compared with younger patients, elderly dyslipidaemic patients are at a higher risk for clinically relevant pDDIs, mainly because of a higher number of drugs prescribed. In addition, patients aged > or = 75 years were prescribed more drugs with a high potential for DDIs, especially drugs used for the treatment of arrhythmias and heart failure. The risk for adverse reactions associated with pDDIs may often be reduced by dose adjustment, close monitoring or selection of an alternative drug.

Prevalence of potentially inappropriate medication use in elderly patients: comparison between general medical and geriatric wards.

BACKGROUND AND OBJECTIVE: Inappropriate drug use is one of the risk factors for adverse drug reactions in the elderly. We hypothesised that, in elderly patients, geriatricians are more aware of potentially inappropriate medications (PIMs) and may replace or stop PIMs more frequently compared with internists. We therefore evaluated and compared the prevalence of PIMs as well as anticholinergic drug use throughout hospital stay in elderly patients admitted to a medical or geriatric ward. METHODS: In this retrospective cross-sectional study, 800 patients aged > or =65 years admitted to a general medical or geriatric ward of a 700-bed teaching hospital in Switzerland during 2004 were included. PIMs were identified using the Beers criteria published in 2003. The prevalence of anticholinergic drug use was assessed based on drug lists published in the literature. RESULTS: The prevalence of use of PIMs that should generally be avoided was similar in medical and geriatric inpatients both at admission (16.0% vs 20.8%, respectively; p = 0.08) and at discharge (13.3% vs 15.9%, respectively; p = 0.31). In contrast to medical patients, the reduction in the prevalence of use of PIMs between admission and discharge in geriatric patients reached statistical significance (p < 0.05). Overall, the three most prevalent inappropriate drugs/drug classes were amiodarone, long-acting benzodiazepines and anticholinergic antispasmodics. At admission, the prevalence of use of PIMs related to a specific diagnosis was not significantly different between patients hospitalised to a medical or a geriatric ward (14.0% vs 17.5%, respectively; p = 0.17), as compared with the significant difference evident at hospital discharge (11.7% vs 23.7%, respectively; p < 0.001). This was largely because of a higher prescription rate of platelet aggregation inhibitors in combination with low-molecular-weight heparins and benzodiazepines in patients with a history of falls and syncope. The proportions of patients taking anticholinergic drugs in medical and geriatric patients at admission (13.0% vs 17.5%, respectively; p = 0.08) and discharge (12.2% vs 16.5%, respectively; p = 0.10) were similar. CONCLUSION: Inappropriate drug use as defined by the Beers criteria was common in both medical and geriatric inpatients. Compared with internists, geriatricians appear to be more aware of PIMs that should generally be avoided, but less aware of PIMs related to a specific diagnosis, and of the need to avoid anticholinergic drug use. However, the results of this study should be interpreted with caution because some of the drugs identified as potentially inappropriate may in fact be beneficial when the patient's clinical condition is taken into consideration.

Lichenoid eruption associated with the use of nebivolol.

OBJECTIVE: To report a case of lichenoid drug eruption (LDE) after starting antihypertensive treatment with nebivolol, a cardioselective beta-blocker. CASE SUMMARY: Five weeks after starting treatment with nebivolol, a 62-year-old woman presented with erythematous papules on both extremities and skin lesions spreading over the back. She was not being treated with any other drugs. Because the administration of levocetirizine, topical methylprednisolone, and systemic prednisone was unsuccessful, the treatment was stopped and the lesions were biopsied. The histopathological features of the lesions were consistent with LDE. After withdrawal of nebivolol and subsequent readministration of topical methylprednisolone and systemic prednisone, the skin lesions resolved within 12 days. Assessment of the causality revealed a probable relationship between nebivolol and the lichenoid eruptions. DISCUSSION: Although beta-blockers can be associated with LDE, as of July 7, 2006, this has not been previously reported with nebivolol. T cells invading the dermis are considered to be responsible for epidermal destruction associated with LDE, as has been described for lichenoid forms of chronic graft versus host disease and idiopathic lichen ruber planus. CONCLUSIONS: Nebivolol can cause LDE, as has been reported with other beta-blockers. The underlying mechanism appears to be T cell-mediated. Cross-reactivity with other beta-blockers cannot be excluded; therefore, the risk of recurrent LDE should be weighed carefully against the clinical benefit before switching to another beta-blocker.

Life-threatening hemorrhage after dalteparin therapy in a patient with impaired renal function.

Dalteparin and other low-molecular-weight heparins are frequently used for the treatment of deep vein thrombosis and for other indications. Unlike unfractionated heparin (UFH), dalteparin is mainly cleared through the kidney; therefore, it can accumulate in patients with impaired renal function, increasing the risk of hemorrhage. An 84-year-old woman with chronic renal failure was hospitalized because of stenosis of a femorofibular bypass in her right leg. Peripheral transluminal angioplasty was performed successfully. Later the same day, Doppler sonography revealed deep vein thrombosis of the left lower leg. Treatment with dalteparin was started. The patient was discharged home 3 days later, with dalteparin to be continued at home. One day later, the patient was rehospitalized because of a pronounced hematoma on her flank. Her hemoglobin level had dropped to 5.5 g/dl. Treatment with dalteparin was stopped, and protamine 2500 U and two transfusions of packed red blood cells were administered. Treatment with UFH and oral anticoagulants were started because of a persistent risk for venous thrombosis. Thereafter, the patient's hemoglobin level remained stable, and no further bleeding episodes occurred. As long as systematic studies of the efficacy and safety of dalteparin in patients with severe renal impairment are lacking, dalteparin should be avoided or used only with close monitoring of antifactor Xa activity in these patients. As an alternative, UFH can be used because monitoring of UFH is well established and easier than it is with dalteparin. Renal impairment does not notably influence the short elimination half-life of UFH, which unlike that of dalteparin or other low-molecular-weight heparins allows for rapid dosage adjustments to prevent hemorrhage.

[Dealing with adverse drug reactions in dentistry. Procedures on encountering adverse drug reactions and goal of the Swiss Pharmacovigilance system]. / Umgang mit unerwünschten Arzneimittelwirkungen in der zahnärztlichen Praxis. Vorgehensweise beim Auftreten von unerwünschten Arzneimittelwirkungen und Zweck des schweizerischen Pharmacovigilance-Systems.

Dentists may be confronted with adverse drug reactions (ADRs) in their dental practice, and are--like other health professionals--obliged to report certain ADRs. The aim of this article is to sensitise dentists for this topic, to show how to proceed in case of a supposed ADR, and to emphasise the importance of spontaneous reporting of ADRs. ADRs may not always be clearly distinguished from symptoms of underlying diseases, and in cases of polypharmacy multiple drugs may be responsible for the reaction. It is therefore important to get a detailed medical history, and to establish a temporal relationship between start of a therapy and appearance of the symptom. Information from the medical literature, exclusion of other possible causes, and identification of risk factors help to confirm a causal relationship between a suspected drug and an observed reaction. In Switzerland severe and unexpected ADRs have to be reported to one of the regional Pharmacovigilance centres with the yellow ADR reporting form from Swissmedic. The spontaneous reports of ADRs help to early identify new problems of a drug therapy, and permit to take measures to minimise the risk.

Lithium intoxication as a result of an interaction with rofecoxib.

OBJECTIVE: To report the occurrence of lithium intoxication in a patient with bipolar disorder after adding rofecoxib to the medication regimen. CASE SUMMARY: A 68-year-old woman with bipolar disorder under long-term treatment with lithium, carbamazepine, pipamperon, and mirtazapine was prescribed rofecoxib 25 mg twice daily for the treatment of leg pain. Within one week, she showed progressive hypokinesia and tremor, which was treated with propranolol. Subsequently, she developed bradycardia, necessitating treatment with isoproterenol. Her lithium serum concentration had doubled compared with those before rofecoxib, and her renal function had deteriorated. After stopping lithium and rofecoxib, her laboratory values and neurologic signs improved or normalized within 2 days. An objective causality assessment revealed a probable relationship between concomitant use of the drugs and the resulting symptoms. DISCUSSION: As of May 24, 2004, only 3 cases of reversible lithium intoxication as a result of a possible interaction with rofecoxib or celecoxib have been previously reported. The mechanism of the interaction between lithium and cyclooxygenase (COX) 2 selective inhibitors is most probably related to inhibition of renal synthesis of prostaglandins, which are important for the maintenance of renal perfusion and tubular function. Impairment of renal blood flow, leading to a decrease in the glomerular filtration rate, and increased proximal tubular absorption are the most likely mechanisms by which COX-2 selective inhibitors reduce lithium clearance. CONCLUSIONS: Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.

Potential drug-drug interactions in the medication of medical patients at hospital discharge.

OBJECTIVE: Information on the frequency of drug combinations with the potential to induce dangerous drug-drug interactions (DDIs) in patients discharged from the hospital is scarce. With the present study, we assessed the frequency and potential clinical significance of DDIs in the prescriptions of discharged medical patients. METHODS: We retrospectively screened the medication for potential DDIs of 500 patients consecutively discharged with at least two prescriptions using a computerised drug-interaction program. RESULTS: The 500 patients (56.6% male, mean age 67.0+/-15.9 years, median length of stay 13 days) were prescribed a median of six drugs (range 2-18) at discharge. Three hundred patients (60.0%; 95% confidence interval 55.7-64.3%) had at least one potentially interacting drug combination. Of 747 potential DDIs at discharge overall, 402 (53.8%) were new at the time of discharge due to a change of the medication during the hospital stay. Of these, 72 (17.9%) were of potentially minor, 281 (69.9%) of moderate and 49 (12.2%) of major severity. Of 44 patients with a potential DDI with major severity, 1 patient was re-hospitalised within 2 months after discharge due to a probable drug-related problem associated with the potential DDI. CONCLUSIONS: Using a computerised drug-interaction program, a high proportion of patients was detected with at least one potential DDI in the medication prescribed at discharge. However, the proportion of DDIs associated with potentially relevant clinical consequences appeared to be relatively low.

Outcome differences in younger and older patients with laryngeal cancer: a retrospective case-control study.

PURPOSE: Younger or older age has a significant impact on the outcome of patients with head and neck cancer. However, the data regarding outcomes based on age are conflicting. The aim of this article is to determine the impact of age on the outcome of laryngeal cancer. MATERIALS AND METHODS: A retrospective study was performed including all patients with squamous cell carcinoma of the larynx for over a 9-year period. The patients were divided into 3 groups based on age. The younger age group included patients 40 years of age and younger, the older group included patients over 80 years of age, and the remaining patients served as the control group. Descriptive statistics were used to summarize study data. Nonparametric quantitative and qualitative analyses were performed using the Mann-Whitney U test and Fisher's exact test, respectively. Survival analysis was performed using the generalized Wilcoxon test. The Cox proportional hazards model was used for multivariate analysis. RESULTS: Of the 209 patients with laryngeal carcinoma presenting to our institution over a 9-year period, 20 (10%) were < or =40 years and 15 (7%) were > or =80 years of age. No differences in TNM stage at presentation, treatment, or treatment-associated complications were observed based on age. However, younger patients were less likely to report tobacco (50%; P < .001) or alcohol (57%; P = .03) use and more likely to have human immunodeficiency virus infection (50%; P< .001). Older patients showed a trend toward having a worse baseline medical status. Recurrence was significantly more common in older patients (P = .02) and cause-specific survival significantly poorer for both younger and older patients (P = .002). CONCLUSIONS: The presentation and outcome of laryngeal cancer is influenced by the age at presentation. The differences may be related exact reason for the observed survival differences needs to be determined.

The impact of comorbidity and age on survival with laryngeal cancer.

Previous studies have evaluated the effects of comorbidity on survival in patients with cancer. We applied the Charlson comorbidity index (CCI) to a cohort of patients with laryngeal cancer to validate its use and to assess the prognostic impact of age. Our study population consisted of 152 patients with laryngeal cancer who were seen over a 10-year period. Patients were assigned CCI scores and were categorized into low- and high-grade comorbidity groups for comparison. Age adjustments were performed by adding 1 point to the Charlson score for each decade over the median age. Low- vs. high-grade comorbidity was a valid predictor of survival independent of TNM (tumor, nodes, and metastases) stage. Low-grade comorbidity was present in 126 patients; their median survival was 41 months. High-grade comorbidity was present in 26 patients; their median survival was 8 months (p = 0.0002). The addition of the age factor to the CCI did not improve our prognostic ability. There was no difference in CCI groups with respect to tobacco and alcohol use, gender, treatment modality, or mean time to recurrence. The incidence and severity of complications were also similar in the two groups. We conclude that the CCI is a strong predictor of survival in patients with laryngeal cancer. The confounding effects of comorbidity should be considered in the TNM staging of laryngeal cancer to improve our prognostic ability. Further investigations are necessary to assess the validity of this index in patients with other head and neck cancers.