Scant literature exists on the treatment of infection after interbody fusion. Some authors advocate removal of the interbody grafts. Salvage of the grafts was possible in 92.3% (12 of 13) of the infections in a series of 326 consecutive patients with degenerative spinal diseases treated by three surgeons. Posterior interbody fusion and posterolateral instrumented fusion was performed in 267 patients and anterior interbody fusion was done in 59 patients. Eight infections in the first group (3%) and six in the second group (10.1%) were identified. Mean followup was 18 months (range, 12-38 months). All infections were early, presenting at a mean of 18 days (range, 11-28 months). All but one infection were in the posterior wound and deep. A high number of risk factors were present in these patients. Initial treatment included wound debridement and broad spectrum antibiotics, until culture results indicated the final antibiotic regimen. Infection recurred as osteomyelitis in one patient with multiple previous surgeries and anterior/posterior fusion. This was treated with removal of the posterior instrumentation and the interbody graft and extensive anterior/posterior reconstruction. Clinical outcomes were good in 10 patients, fair in two and poor in one using the Stauffer-Coventry scale. One pseudarthrosis was identified in a patient with anterior interbody fusion at final followup. Salvage of the interbody graft and retaining the instrumentation was safe in most cases in the presented series and did not adversely affect outcome.

METHODS

Therapeutic study, level IV (case series). Please see the Guidelines for Authors for a complete description of levels of evidence.

BACKGROUND

Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years.

RESULTS

We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4 ± 3.8 y, range 1-20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19-1.37) to 1.05 (1.00-1.09) and from 1.39 (1.23-1.56) to 1.01 (0.93-1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6-1.7, p<0.001) and 1.9% (0.8-2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%-6.9% (RR 0.96 and 0.90 each year) and 7.0%-7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study.

CONCLUSIONS

The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients. Please see later in the article for the Editors' Summary.

Kersa HDSS was established in 12 sub-districts of Kersa district, Eastern Hararge, Oromia Region, Ethiopia. The site is principally rural with two small towns (Kersa and Weter). The baseline census was conducted in 2007 and since then has been updated every 6 months, with registration of demographic and health events. Data are entered into the HRS-2 relational database. At baseline a total of 10,085 houses, 10,522 households and 50,830 people were registered. The sex ratio and number of persons per household were 1.0 and 5.1, respectively. At the end of 2013, the population was 60,694. Up to the end of 2013, 12,571 births and 3143 deaths were registered, respectively. Over 85% of births and deaths occurred at home. The annual net population growth ranges from 0.06 to 1.6. The majority of the population in Kersa are not working age group; hence the dependency ratio in most of the years is below 1. The total fertility rate ranges from 4.0 to 5.3. A reduction in neonatal, infant and under-five mortalities was observed. For all deaths, verbal autopsies were done. Tuberculosis is the leading cause of death among adults and malnutrition is the leading cause of death among children aged under 5 years. Kersa HDSS is ready to collaborate with interested researchers on health and demographic issues. For further details please visit: [http://www.haramaya.edu.et/research/projects/kds-hrc/].

Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Therefore, considerable efforts have been made in developing and validating biophysical methods to elucidate the complex structure of the Env-spike glycoprotein, with its combination of glycan and protein epitopes. We illustrate here how the application of robust biophysical methods have transformed our understanding of the structure and function of the HIV Env spike and stimulated innovation in vaccine design strategies that takes into account the essential glycan components Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mentalizing is the capacity to understand others and oneself in terms of internal mental states. It is assumed to be underpinned by four dimensions: automatic-controlled, internally-externally focused, self-other, and cognitive-affective. Research suggests that mental disorders are associated with different imbalances in these dimensions. Addressing the quality of mentalizing as part of psychosocial treatments may be helpful for individuals with various mental disorders. We suggest that mentalizing is a helpful transtheoretical and transdiagnostic concept to explain vulnerability to psychopathology and its treatment. This review summarizes the mentalizing approach to psychopathology from a developmental socioecological evolutionary perspective. We then focus on the application of the mentalizing approach to personality disorders, and we review studies that have extended this approach to other types of psychopathology, including depression, anxiety, and eating disorders. We summarize core principles of mentalization-based treatments and preventive interventions and the evidence for their effectiveness. We conclude with recommendations for future research. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 16 is May 7, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

BACKGROUND

Finding the most appropriate strategy for the prevention of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in young children is essential in countries like Niger with annual "hunger gaps." Options for large-scale prevention include distribution of supplementary foods, such as fortified-blended foods or lipid-based nutrient supplements (LNSs) with or without household support (cash or food transfer). To date, there has been no direct controlled comparison between these strategies leading to debate concerning their effectiveness. We compared the effectiveness of seven preventive strategies-including distribution of nutritious supplementary foods, with or without additional household support (family food ration or cash transfer), and cash transfer only-on the incidence of SAM and MAM among children aged 6-23 months over a 5-month period, partly overlapping the hunger gap, in Maradi region, Niger. We hypothesized that distributions of supplementary foods would more effectively reduce the incidence of acute malnutrition than distributions of household support by cash transfer.

RESULTS

We conducted a prospective intervention study in 48 rural villages located within 15 km of a health center supported by Forum Santé Niger (FORSANI)/Médecins Sans Frontières in Madarounfa. Seven groups of villages (five to 11 villages) were allocated to different strategies of monthly distributions targeting households including at least one child measuring 60 cm-80 cm (at any time during the study period whatever their nutritional status): three groups received high-quantity LNS (HQ-LNS) or medium-quantity LNS (MQ-LNS) or Super Cereal Plus (SC+) with cash (€38/month [US$52/month]); one group received SC+ and family food ration; two groups received HQ-LNS or SC+ only; one group received cash only (€43/month [US$59/month]). Children 60 cm-80 cm of participating households were assessed at each monthly distribution from August to December 2011. Primary endpoints were SAM (weight-for-length Z-score [WLZ]<-3 and/or mid-upper arm circumference [MUAC]<11.5 cm and/or bipedal edema) and MAM (-3≤WLZ<-2 and/or 11.5≤MUAC<12.5 cm). A total of 5,395 children were included in the analysis (615 to 1,054 per group). Incidence of MAM was twice lower in the strategies receiving a food supplement combined with cash compared with the cash-only strategy (cash versus HQ-LNS/cash adjusted hazard ratio [HR]=2.30, 95% CI 1.60-3.29; cash versus SC+/cash HR=2.42, 95% CI 1.39-4.21; cash versus MQ-LNS/cash HR=2.07, 95% CI 1.52-2.83) or with the supplementary food only groups (HQ-LNS versus HQ-LNS/cash HR=1.84, 95% CI 1.35-2.51; SC+ versus SC+/cash HR=2.53, 95% CI 1.47-4.35). In addition, the incidence of SAM was three times lower in the SC+/cash group compared with the SC+ only group (SC+ only versus SC+/cash HR=3.13, 95% CI 1.65-5.94). However, non-quantified differences between groups, may limit the interpretation of the impact of the strategies.

CONCLUSIONS

Preventive distributions combining a supplementary food and cash transfer had a better preventive effect on MAM and SAM than strategies relying on cash transfer or supplementary food alone. As a result, distribution of nutritious supplementary foods to young children in conjunction with household support should remain a pillar of emergency nutritional interventions. Additional rigorous research is vital to evaluate the effectiveness of these and other nutritional interventions in diverse settings.

BACKGROUND

ClinicalTrials.gov NCT01828814 Please see later in the article for the Editors' Summary.

BACKGROUND

Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.

RESULTS

The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR] = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.

CONCLUSIONS

Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.

The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal, and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. WIREs Nanomed Nanobiotechnol 2016, 8:776-791. doi: 10.1002/wnan.1390 For further resources related to this article, please visit the WIREs website.

BACKGROUND

The diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection.

RESULTS

Adults with cough ≥2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., "on the spot") the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%-76.5%) and 65.8% (348/529, 95% CI 61.6%-69.8%) sensitive (p<0.001) and 90.9% (1,660/1,826, 95% CI 89.5%-92.2%) and 98% (1,790/1,826, 95% CI 97.3%-98.6%) specific (p<0.001). Using three LED-FM or three ZN smears per patient was 77% (408/529, 95% CI 73.3%-80.6%) and 70.5% (373/529, 95% CI 66.4%-74.4%, p<0.001) sensitive and 88.1% (95% CI 86.5%-89.6%) and 96.5% (95% CI 96.8%-98.2%, p<0.001) specific. The sensitivity/specificity of ZN smear microscopy and LED-FM did not vary between SMS and SSM.

CONCLUSIONS

LED-FM had higher sensitivity but, in this study, lower specificity than ZN smear microscopy for diagnosis of pulmonary TB. Performance was independent of the scheme used for collecting specimens. The introduction of LED-FM needs to be accompanied by appropriate training, quality management, and monitoring of performance in the field.

BACKGROUND

Current Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Spinal infections affect the vertebral bodies, the intervertebral disks, the spinal canal, and the paravertebral soft tissues and structures. A delay in diagnosis can result in spine deformity, substantial neurologic complications, and even death. Because of this, a high level of awareness is required by physicians in order to diagnose infections of the spine promptly. Advances in medical microbiologic testing and newer imaging methods have contributed considerably to the medical treatment of these infections. Through careful followup, less invasive approaches orchestrated by a multidisciplinary team that includes a spine surgeon, an infectious diseases specialist, and a neuroradiologist may be sufficient to treat patients with these infections. Research done through multidisciplinary collaborations will further advance our knowledge for the successful treatment of spinal infections.

METHODS

Level V (expert opinion). Please see the Guidelines for Authors for a complete description of levels of evidence.

The concept that mitochondria are highly dynamic is as widely accepted as it is untrue for a number of important contexts. Healthy mitochondria of the most energy-dependent and mitochondrial-rich mammalian organ, the heart, only rarely undergo fusion or fission and are seemingly static within cardiac myocytes. Here, we revisit mitochondrial dynamism with a fresh perspective developed from the recently discovered multifunctionality of mitochondrial fusion proteins and newly defined mechanisms for direct cross talk between mitochondrial dynamics, biogenesis, quality control, and trafficking pathways. Insights gained from comparing static mitochondrial biology in cardiac myocytes and dynamic mitochondrial biology in neurons are reviewed with the goal of understanding contextual fallacies of overly generalized characterizations of these essential and intriguing organelles. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

This research investigated the effects of a nutrition education program on dietary behavior and nutrition knowledge among elementary school-aged children participating in a Social Cognitive Theory-based nutrition education program. Participants included 1100 second-grade and third-grade students selected by convenience-type sampling from public schools in Alabama. A preassessment and postassessment control group design assessed dietary behavior and nutrition knowledge using Pizza Please, a specially designed interactive evaluation tool. A 2 x 2 mixed analysis of variance was used to analyze data. Children in the treatment group exhibited significantly (p < .001) greater improvement in overall dietary behaviors such as consumption of dairy products, fruits, and vegetables, than children in the control group. Children in the treatment group exhibited significantly (p < .001) greater improvement in nutrition knowledge, including Food Guide Pyramid understanding, nutrient-food association, and nutrient-job association, than children in the control group. Results suggest that nutrition education programs that teach positive dietary messages potentially can improve dietary behavior and increase nutrition knowledge in children.

BACKGROUND

Potentially inappropriate prescribing (PIP) is commonly seen amongst the older population in all clinical settings, as indicated by several prevalence studies in several countries. Quantitative work such as this confirms that this is a global public health problem likely to grow in tandem with ageing of the global population. However, less attention has been focused on why it is happening and how it can be prevented.

OBJECTIVE

The objective of this paper is to synthesise qualitative studies that explore PIP in older patients, in an effort to understand why it happens from a prescriber's perspective and to generate a new theory to guide future interventional studies aimed at minimising it in older people. To date, there is no published systematic synthesis of this type.

METHODS

Papers were deemed suitable for inclusion if they used qualitative methods, explored some area of PIP in patients over 65 years of age, were published in English and had available published abstracts. Four databases were systematically searched for papers published up to the end of April 2013: PubMed, Embase, CINAHL and Web of Knowledge. No date restrictions were applied. Key words searched were: Qualitative AND (Inappropriate* OR Appropriate* OR Safe) AND (Elderly OR Aged OR Geriatric* OR Old*) AND Prescri*. Reference lists were then searched for other suitable papers. Critical Appraisal Skills Programme criteria were used to assess quality. Meta-ethnography was used to synthesise the papers.

RESULTS

Out of 624 papers identified, seven papers were deemed relevant. Four key concepts were identified as being causal factors in PIP: (1) the need to please the patient, (2) feeling of being forced to prescribe, (3) tension between prescribing experience and prescribing guidelines and (4) prescriber fear. These were re-interpreted in a line of argument synthesis indicating that some doctors have self-perceived restrictions with regard to prescribing appropriately because of a combination of factors, rather than any one dominant factor.

CONCLUSIONS

Prevention of PIP may be favourably influenced by addressing the key interactive determinants of inappropriate prescribing behaviour.

OBJECTIVE

To compare image quality and visualization of normal structures and lesions in brain computed tomography (CT) with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP) reconstruction techniques in different X-ray tube current-time products.

METHODS

In this IRB-approved prospective study, forty patients (nineteen men, twenty-one women; mean age 69.5 ± 11.2 years) received brain scan at different tube current-time products (300 and 200 mAs) in 64-section multi-detector CT (GE, Discovery CT750 HD). Images were reconstructed with FBP and four levels of ASIR-FBP blending. Two radiologists (please note that our hospital is renowned for its geriatric medicine department, and these two radiologists are more experienced in chronic cerebral vascular disease than in neoplastic disease, so this research did not contain cerebral tumors but as a discussion) assessed all the reconstructed images for visibility of normal structures, lesion conspicuity, image contrast and diagnostic confidence in a blinded and randomized manner. Volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded. All the data were analyzed by using SPSS 13.0 statistical analysis software.

RESULTS

There was no statistically significant difference between the image qualities at 200 mAs with 50% ASIR blending technique and 300 mAs with FBP technique (p>.05). While between the image qualities at 200 mAs with FBP and 300 mAs with FBP technique a statistically significant difference (p<.05) was found.

CONCLUSIONS

ASIR provided same image quality and diagnostic ability in brain imaging with greater than 30% dose reduction compared with FBP reconstruction technique.

BACKGROUND

Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five.

RESULTS

We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]).

CONCLUSIONS

Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions.

BACKGROUND

ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary.

BACKGROUND

Topotecan activity was evaluated for the treatment of malignant glioma.

METHODS

Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throughout text.]at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3).

RESULTS

Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression.

CONCLUSIONS

These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.

BACKGROUND

Plantar heel pain causes soreness or tenderness of the sole of the foot under the heel, which sometimes extends into the medial arch. The prevalence and prognosis are unclear, but the symptoms seem to resolve over time in most people.

METHODS

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for plantar heel pain? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS

We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS

In this systematic review we present information relating to the effectiveness and safety of the following interventions: casted orthoses (custom-made insoles), corticosteroid injection (alone, or plus non-steroidal anti-inflammatory drugs), extracorporeal shock wave therapy, heel cups, heel pads (alone or with corticosteroid injection), lasers, local anaesthetic injection (alone or with corticosteroid injection), night splints plus non-steroidal anti-inflammatory drugs, stretching exercises, surgery, taping, and ultrasound.

BACKGROUND

The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools.

RESULTS

We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.10 [1.02-1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.09 [1.05-1.14]).

CONCLUSIONS

Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors' Summary.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of author Stanley Rapoport, with approval from Biological Psychiatry Editor, John H. Krystal, MD. The National Institutes of Health has found that Dr. Jagadeesh S. Rao engaged in research misconduct by falsifying data in Figures 1, 3, and 5 of the aforementioned manuscript. No other authors were implicated in the data falsification

In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH-sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH-sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co-delivery of cargos, dual pH-sensitive nanocarriers, dual/multi stimuli-responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer's. In order to design an optimized system, it is necessary to understand the various pH-responsive micro/nanoparticles and the different mechanisms of pH-sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers. WIREs Nanomed Nanobiotechnol 2016, 8:696-716. doi: 10.1002/wnan.1389 For further resources related to this article, please visit the WIREs website.

Paradoxically, individuals with autism spectrum conditions have been characterized as both impaired in self-referential cognitive processing, yet also egocentric. How can the self in autism be both 'absent' (i.e., impaired self-referential cognition), yet 'all too present' (i.e., egocentric)? In this paper, we first review evidence in support of both claims. Second, we highlight new evidence illustrating atypical function of neural systems underlying self-representation in autism. We suggest that egocentrism and impaired self-referential cognition are not independent phenomena. Instead, both egocentrism and impaired self-referential cognition in autism can be resolved as expressions of one common mechanism linked to the atypical function of neural circuitry coding for self-relevant information. We discuss how autism provides a unique window into the neurodevelopmental mechanisms enabling a critical developmental transition in self-awareness. This transition involves a dual understanding that one is similar to, yet distinct from others. The neural and cognitive basis of this developmental transition is central to understanding the development of social cognition as well as the paradox of the autistic self and its relation to social impairment in autism. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

BACKGROUND

Oncolytic viruses that specifically target tumor cells are promising anti-cancer therapeutic agents. The interaction between an oncolytic virus and tumor cells is amenable to mathematical modeling using adaptations of techniques employed previously for modeling other types of virus-cell interaction.

RESULTS

A complete parametric analysis of dynamic regimes of a conceptual model of anti-tumor virus therapy is presented. The role and limitations of mass-action kinetics are discussed. A functional response, which is a function of the ratio of uninfected to infected tumor cells, is proposed to describe the spread of the virus infection in the tumor. One of the main mathematical features of ratio-dependent models is that the origin is a complicated equilibrium point whose characteristics determine the main properties of the model. It is shown that, in a certain area of parameter values, the trajectories of the model form a family of homoclinics to the origin (so-called elliptic sector). Biologically, this means that both infected and uninfected tumor cells can be eliminated with time, and complete recovery is possible as a result of the virus therapy within the framework of deterministic models.

CONCLUSIONS

Our model, in contrast to the previously published models of oncolytic virus-tumor interaction, exhibits all possible outcomes of oncolytic virus infection, i.e., no effect on the tumor, stabilization or reduction of the tumor load, and complete elimination of the tumor. The parameter values that result in tumor elimination, which is, obviously, the desired outcome, are compatible with some of the available experimental data.

METHODS

This article was reviewed by Mikhail Blagosklonny, David Krakauer, Erik Van Nimwegen, and Ned Wingreen.

BACKGROUND

Reviewed by Mikhail Blagosklonny, David Krakauer, Erik Van Nimwegen, and Ned Wingreen. For the full reviews, please go to the Reviewers' comments section.