BackgroundMalaria in pregnancy poses a major public health problem in Indonesia with an estimated six million pregnancies at risk of Plasmodium falciparum or Plasmodium vivax malaria annually. In 2010, Indonesia introduced a screen and treat policy for the control of malaria in pregnancy at first antenatal visit using microscopy or rapid diagnostic tests (RDTs). A diagnostic study was conducted in Sumba, Indonesia to compare the performance of four different RDTs in predominately asymptomatic pregnant women under field condition.MethodsWomen were screened for malaria at antenatal visits using field microscopy and four HRP-2/pLDH combination RDTs (Carestart™, First-Response®, Parascreen® and SD-Bioline®). The test results were compared with expert microscopy and nested PCR. End user experience of the RDTs in the field was assessed by questionnaire.ResultsOverall 950 were recruited and 98.7 % were asymptomatic. The prevalence of malaria was 3.0–3.4 % by RDTs, and 3.6, 5.0 and 6.6 % by field microscopy, expert microscopy and PCR, respectively. The geometric-mean parasite density was low (P. falciparum = 418, P. vivax = 147 parasites/µL). Compared with PCR, the overall sensitivity of the RDTs and field microscopy to detect any species was 24.6–31.1 %; specificities were >98.4 %. Relative to PCR, First-Response® had the best diagnostic accuracy (any species): sensitivity = 31.1 %, specificity = 98.9 % and diagnostic odds ratio = 39.0 (DOR). The DOR values for Carestart™, Parascreen®, SD-Bioline®, and field microscopy were 23.4, 23.7, 23.5 and 29.2, respectively. The sensitivity of Pan-pLDH bands to detect PCR confirmed P. vivax mono-infection were 8.6–13.0 %. The sensitivity of the HRP-2 band alone to detect PCR confirmed P. falciparum was 10.3–17.9 %. Pan-pLDH detected P. falciparum cases undetected by the HRP-2 band resulting in a better test performance when both bands were combined. First Response® was preferred by end-users for the overall practicality.ConclusionThe diagnostic accuracy to detect malaria among mostly asymptomatic pregnant women and perceived ease of use was slightly better with First-Response®, but overall, differences between the four RDTs were small and performance comparable to field microscopy. Combination RDTs are a suitable alternative to field microscopy to screen for malaria in pregnancy in rural Indonesia. The clinical relevance of low density malaria infections detected by PCR, but undetected by RDTs or microscopy needs to be determined.
Many upper gastrointestinal (GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines, uncertainty about etiology of symptoms, and therapy failure. Unfiltered open-access referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First, we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed.
Smith–Lemli–Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7‐dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7‐dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8–1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS‐phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8–1 G > T). Two patients, homozygous for the IVS8–1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS‐phenotype disclosed compound heterozygosity of the IVS8–1 G > C mutation in combination with different novel and known missense mutations.
Background. Cholecystectomy does not relieve abdominal symptoms in up to 40% of patients. With 700,000 cholecystectomies performed in the US, annually, about 280,000 patients are left with symptoms, making this a serious problem. We performed a systematic review to determine the different etiologies of long-term postcholecystectomy symptoms with the aim to provide guidance for clinicians treating these patients. Methods. A systematic search of the literature was performed using MEDLINE, EMBASE, and Web of Science. Articles describing at least one possible etiology of long-term symptoms after a laparoscopic cholecystectomy were included in this review. Long-term symptoms were defined as abdominal symptoms that were present at least four weeks after cholecystectomy, either persistent or incident. The etiologies of persistent and incident symptoms after LC and the mechanism or hypothesis behind the etiologies are provided. If available, the prevalence of the discussed etiology is provided. Results. The search strategy identified 3320 articles of which 130 articles were included. Etiologies for persistent symptoms were residual and newly formed gallstones (41 studies, prevalence ranged from 0.2 to 23%), coexistent diseases (64 studies, prevalence 1-65%), and psychological distress (13 studies, no prevalence provided). Etiologies for incident symptoms were surgical complications (21 studies, prevalence 1-3%) and physiological changes (39 studies, prevalence 16-58%). Sphincter of Oddi dysfunction (SOD) was reported as an etiology for both persistent and incident symptoms (21 studies, prevalence 3-40%). Conclusion. Long-term postcholecystectomy symptoms vary amongst patients, arise from different etiologies, and require specific diagnostic and treatment strategies. Most symptoms after cholecystectomy seem to be caused by coexistent diseases and physiological changes due to cholecystectomy. The outcome of this research is summarized in a decision tree to give clinical guidance on the treatment of patients with symptoms after cholecystectomy.
Cholecystolithiasis and functional gastrointestinal disorders are both highly prevalent in the industrialized world and may exist concomitantly. The presence of both conditions impedes identification of the source of symptoms, leading to a risk of ineffective cholecystectomies with lack of symptom resolution. We carried out a systematic review and meta-analysis to determine the prevalence of dyspepsia in patients with uncomplicated cholecystolithiasis. The electronic databases Medline, Embase, and Web of Science were searched for articles reporting the prevalence of dyspepsia in adults (≥18 years) with uncomplicated cholecystolithiasis. Pooled prevalence and 95% confidence interval were calculated. I 2 statistics were used to determine heterogeneity and the Methodological Evaluation of Observational Research criteria were applied for quality assessment. The study was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Of the 1696 studies evaluated, 13 reported the prevalence of dyspepsia in a total of 1227 cholecystolithiasis patients seeking medical care. The pooled prevalence of dyspepsia in patients with cholecystolithiasis was 65.7% (95% confidence interval: 51-79%). However, heterogeneity was large across studies. Overall, three studies used validated diagnostic criteria. Variation in diagnostic measures significantly influenced the prevalence of dyspepsia. In conclusion, symptoms similar to those of functional gastrointestinal disorders are common in patients with cholecystolithiasis, obscuring the source of abdominal complaints. Tools to select patients who will benefit from cholecystectomy are paramount to prevent ineffective surgery.
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