Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events

BackgroundIncreased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV₁) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.MethodsParticipants ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV₁ of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days.ResultsOf 97 participants, 94 (96.9%) completed the study. The primary endpoint was incidence of predefined respiratory adverse events of special interest (chest discomfort, dyspnea, respiration abnormal, asthma, bronchial hyperreactivity, bronchospasm, and wheezing): tezacaftor/ivacaftor, 14.0%; placebo, 21.3%. The adverse events were mild or moderate in severity. None were serious or led to treatment interruption or discontinuation. Overall, the discontinuation rate was similar between groups. The mean (SD) ppFEV₁ at baseline was 44.6% (16.1%) with tezacaftor/ivacaftor and 48.0% (18.1%) with placebo. The posterior mean difference in absolute change in ppFEV₁ from baseline to the average value of days 28 and 56 was 2.7 percentage points with tezacaftor/ivacaftor vs placebo.ConclusionsTezacaftor/ivacaftor was generally safe, well tolerated, and efficacious in people ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV₁ of ≥25% and ≤90% who previously discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.     

Isolated hepatic tuberculosis: An uncommon presentation of a common culprit

Hepatic tuberculosis (HTB) is commonly encountered in patients with widespread miliary disease. Isolated affection of the liver is extremely rare. We present a case of a young woman who presented with a subacute afebrile hepatic failure. Investigations including a liver biopsy proved that the presentation was due to granulomatous hepatitis secondary to mycobacterial infection of the liver. It is important that tuberculosis (TB) be kept in mind especially in endemic areas even in atypical clinical scenarios by clinicians, radiologists, and pathologists. Use of anti-tuberculous drugs in such cases is usually successful and must be instituted early.     

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.     

Clinical Efficacy of Subgingivally Delivered 1.2% Atorvastatin in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Atorvastatin (ATV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, statins have shown pleiotropic effects such as anti‐inflammation and bone stimulation. The aim of the present study is to investigate the effectiveness of 1.2% ATV as an adjunct to scaling and root planing (SRP) in the treatment of intrabony defects (IBDs). Methods: Sixty individuals were randomized into two treatment groups: SRP plus 1.2% ATV and SRP plus placebo gel. At baseline and 3, 6, and 9 months, clinical parameters, which included modified sulcus bleeding index, plaque index, probing depth (PD), and clinical attachment level (CAL), were recorded at baseline. Radiologic assessment of IBD fill was done using computer‐aided software at baseline and 6 and 9 months. Results: Mean PD reduction and mean CAL gain were greater in the ATV group than the placebo group at 3, 6, and 9 months. A significantly greater mean percentage of radiographic bone fill was found in the ATV group (35.49% ± 5.50%) compared to the placebo group (1.82% ± 1.32%) after 9 months. Conclusion: ATV as an adjunct to SRP can provide a new direction in the management of IBDs.     

Locally Delivered 1% Metformin Gel in the Treatment of Smokers with Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Metformin (MF) (1,1‐dimethylbiguanide HCl) is one of the most commonly used oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus. Recently, MF has been shown to have bone‐sparing properties. The present study is designed to investigate the effectiveness of MF 1% in an indigenously prepared, biodegradable, controlled‐release gel, as an adjunct to scaling and root planing (SRP) in treatment of vertical defects in smokers with generalized chronic periodontitis (CP). Methods: Fifty patients were categorized into two treatment groups: SRP plus 1% MF and SRP plus placebo. Clinical parameters were recorded at baseline and at 3 and 6 months; they included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 months, intrabony defect (IBD) fill was radiologically assessed using computer software. Results: Mean PD reduction and mean CAL gain were found to be greater in the MF group than the placebo group at all visits. Furthermore, a significantly greater mean percentage of bone fill was found in the MF group (26.17% ± 6.66%) than the placebo sites (3.75% ± 8.06%) (P <0.001). Conclusion: There was greater decrease in mSBI and PD and more CAL gain with significant IBD fill at vertical defect sites treated with SRP plus locally delivered MF, versus SRP plus placebo, in smokers with generalized CP.     

Efficacy of Subgingivally Delivered Simvastatin in the Treatment of Patients With Type 2 Diabetes and Chronic Periodontitis: A Randomized Double‐Masked Controlled Clinical Trial

Background: Simvastatin (SMV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, it has been reported that statins promote bone formation. The present study is designed to investigate the effectiveness of 1.2% SMV in an indigenously prepared, biodegradable, controlled‐release gel as an adjunct to scaling and root planing (SRP) in the treatment of patients with type 2 diabetes and chronic periodontitis (CP). Methods: Thirty‐eight patients were categorized into two treatment groups: SRP plus 1.2% SMV and SRP plus placebo. Clinical parameters were recorded at baseline before SRP and at 3, 6, and 9 months; they included modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 and 9 months, radiologic assessment of intrabony defect (IBD) fill was done using computer‐aided software. Results: Mean PD reduction and mean CAL gain were found to be greater in the SMV group than the placebo group at 3, 6, and 9 months. Furthermore, significantly greater mean percentage of bone fill was found in the SMV group (32.64% ± 12.90%) compared to the placebo group (4.22% ± 9.75%) after 9 months. Conclusion: There was a greater decrease in mSBI and PD and more CAL gain with significant IBD fill at sites treated with SRP plus locally delivered SMV in patients with type 2 diabetes and CP.     

Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal

Background

In Nepal, an estimated 2–4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction.

Methods

In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay.

Results

Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77–95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09–0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04–0.39%) were positive for HBsAg (p = 0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%.

Conclusions

This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued.     

基于笔形束散射核的非均匀模体透射平面散射线分析

目的:利用蒙特卡罗方法分析透射平面上散射光子的物理性质以及非均匀模体厚度对散射核的影响,为基于电子射野影像设备（EPID）的在体剂量验证研究提供基础。方法:利用EGSnrc建立笔形束散射核模型,并模拟获得X射线穿过非均匀模体（水肺水/水骨水模体）以及相应等效厚度水模后30 cm处透射平面上的多种散射线能量注量分布,并分析水肺水/水骨水模体与其等效厚度水模体在散射线能量注量分布上的差异。结果:散射核中一阶康普顿散射线最大能量注量在1×10-4 MeV·cm-2数量级,当离轴距离为8~12 cm时下降至最大值的一半,而散射核中其它散射线能量注量最大值在1×10-5 MeV·cm-2数量级附近或以下。对于水肺水/水骨水模体,散射核能量注量相对偏差变化为±1.2%~±11.5%,且随模体非均匀层厚度增大而增大。结论:散射核中一阶康普顿散射线占比最大,同时也贡献了大部分能量注量相对偏差,在通过散射核来重建非均匀模体后EPID平面上的射线分布时,应着重考虑一阶康普顿散射线对重建结果的影响,并对其进行有效的修正。