Approach to the patient with prediabetes

Prediabetes consists of impaired fasting glucose and/or impaired glucose tolerance and is a significant risk factor for the development of type 2 diabetes, microvascular, and macrovascular disease. The values used to define prediabetes are arbitrary, because prediabetes represents an intermediary category along the continuum from normal glucose levels and tolerance to overt hyperglycemia. The progression from prediabetes to type 2 diabetes occurs over many years, strong evidence to support intervention to delay the progression from prediabetes to diabetes. Large, randomized prospective studies with lifestyle intervention and/or various modes of pharmacotherapy have demonstrated successful delay of diabetes. Several issues in the management of prediabetes remain controversial, such as the role of pharmacotherapy and when to escalate treatment. This article will review some of the issues surrounding the identification and treatment of prediabetes, with an interpretation of the available data to help guide management.     

Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

The impact of post-partum haemorrhage in “near-miss” morbidity and mortality in developing countries

The global maternal mortality ratio (MMR) of 400 per 100,000 live births results in an estimated 529,000 maternal deaths annually. Most of these deaths occur in developing countries and only about 1% in developed countries. Besides mortality data, the identification and accurate documentation of “near-miss” morbidity (a more sensitive index) is extremely important to assess the quality of health care systems. It can suitably guide to adopt appropriate measures to reduce maternal mortality and morbidity. Haemorrhage remains a major cause of maternal mortality in both developing and developed countries followed by anaemia and infection, which are more common in developing countries. Post-partum haemorrhage (PPH) is a frequent complication of delivery. PPH occurred in 10.5% of all live births worldwide resulting in 13,795,000 cases in the year 2000. The case fatality rate for PPH was 1% and there were 132,000 deaths attributable to PPH. Anaemia as a consequence of PPH was estimated to occur in 1.6 million women every year. Thus, the prevention and adequate management of obstetric haemorrhage are likely to result in a significant reduction in the MMR and in the less frequently monitored “near-miss” morbidity. Strategies to be adopted with regard to PPH in developing countries may differ from those routinely available and practised in developed countries because of limited access to health care facilities and low institutional delivery rate in the former countries. Some low cost, simple techniques to prevent and manage PPH are described. These need to be tested in a wider population to determine which is most suitable for a particular area or country. The mortality and “near-miss” morbidity data should be continually assessed and only then will the impact of these strategies be known. First level midwifery care plus backup by well-equipped hospitals must be developed concomitantly. Anyone can conduct a normal delivery when all is going well but only those with good clinical judgement and the necessary skills will be able to anticipate and manage a problem. This is especially important in the context of PPH where the under-estimation of blood loss coupled with the rapidity of development of serious consequences is the key issue.     

Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study

The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996–2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo (n = 1082) or metformin (n = 1073) 850 mg twice daily, or intensive lifestyle intervention (n = 1079). The masked metformin/placebo intervention phase ended approximately 1 year ahead of schedule because of demonstrated efficacy. Primary outcome was reported at 2.8 years. At the end of the DPP, all participants were offered lifestyle education and 88% (n = 2776) of the surviving DPP cohort continued follow-up in the DPPOS. Participants originally assigned to metformin continued to receive metformin, unmasked. The DPP/DPPOS cohort has now been followed for over 15 years with prospective assessment of glycaemic, cardiometabolic, health economic and safety outcomes. After an average follow-up of 2.8 years, metformin reduced the incidence of diabetes by 31% compared with placebo, with a greater effect in those who were more obese, had a higher fasting glucose or a history of gestational diabetes. The DPPOS addressed the longer-term effects of metformin, showing a risk reduction of 18% over 10 and 15 years post-randomisation. Metformin treatment for diabetes prevention was estimated to be cost-saving. At 15 years, lack of progression to diabetes was associated with a 28% lower risk of microvascular complications across treatment arms, a reduction that was no different among treatment groups. Recent findings suggest metformin may reduce atherosclerosis development in men. Originally used for the treatment of type 2 diabetes, metformin, now proven to prevent or delay diabetes, may serve as an important tool in battling the growing diabetes epidemic. Long-term follow-up, currently underway in the DPP/DPPOS, is now evaluating metformin’s potential role, when started early in the spectrum of dysglycaemia, on later-stage comorbidities, including cardiovascular disease and cancer. Trial registration: ClinicalTrials.gov NCT00038727 and NCT00004992.     

Rare coexistence of keratinizing squamous cell carcinoma with xanthogranulomatous pyelonephritis in the same kidney: report of two cases

Squamous cell carcinoma of urinary tract is a rarely encountered tumor. It is more frequently reported in urinary bladder and male urethra than renal pelvis. Squamous cell carcinoma of renal pelvis is usually associated with nephrolithiasis. However, coexistence of keratinizing squamous cell carcinoma with xanthogranulomatous pyelonephritis is exceedingly rare with only one case on record so far. We report two such cases detected incidentally in patients who have undergone nephrectomy for hydronephrosis. The post operative histological evaluation revealed unsuspected squamous cell carcinoma of renal pelvis with concomitant xanthogranulomatous pyelonephritis.     

Safety and efficacy of acupuncture in children: a review of the evidence

Acupuncture has been used therapeutically in China for thousands of years and is growing in prominence in Europe and the United States. In a recent review of complementary and alternative medicine use in the US population, an estimated 2.1 million people or 1.1% of the population sought acupuncture care during the past 12 months. Four percent of the US population used acupuncture at any time in their lives. We reviewed 31 different published journal articles, including 23 randomized controlled clinical trials and 8 meta-analysis/systematic reviews. We found evidence of some efficacy and low risk associated with acupuncture in pediatrics. From all the conditions we reviewed, the most extensive research has looked into acupuncture's role in managing postoperative and chemotherapy-induced nausea/vomiting. Postoperatively, there is far more evidence of acupuncture's efficacy for pediatrics than for children treated with chemotherapy. Acupuncture seems to be most effective in preventing postoperative induced nausea in children. For adults, research shows that acupuncture can inhibit chemotherapy-related acute vomiting, but conclusions about its effects in pediatrics cannot be made on the basis of the available published clinical trials data to date. Besides nausea and vomiting, research conducted in pain has yielded the most convincing results on acupuncture efficacy. Musculoskeletal and cancer-related pain commonly affects children and adults, but unfortunately, mostly adult studies have been conducted thus far. Because the manifestations of pain can be different in children than in adults, data cannot be extrapolated from adult research. Systematic reviews have shown that existing data often lack adequate control groups and sample sizes. Vas et al, Alimi et al, and Mehling et al demonstrated some relief for adults treated with acupuncture but we could not find any well-conducted randomized controlled studies that looked at pediatrics and acupuncture exclusively. Pain is often unresolved from drug therapy, thus there is a need for more studies in this setting. For seasonal allergic rhinitis, we reviewed studies conducted by Ng et al and Xue et al in children and adults, respectively. Both populations showed some relief of symptoms through acupuncture, but questions remain about treatment logistics. Additionally, there are limited indications that acupuncture may help cure children afflicted with nocturnal enuresis. Systematic reviews show that current published trials have suffered from low trial quality, including small sample sizes. Other areas of pediatric afflictions we reviewed that suffer from lack of research include asthma, other neurologic conditions, gastrointestinal disorders, and addiction. Acupuncture has become a dominant complementary and alternative modality in clinical practice today, but its associated risk has been questioned. The National Institutes of Health Consensus Statement states "one of the advantages of acupuncture is that the incidence of adverse effects is substantially lower than that of many drugs or other accepted procedures for the same conditions." A review of serious adverse events by White et al found the risk of a major complication occurring to have an incidence between 1:10,000 and 1:100,000, which is considered "very low." Another study found that the risk of a serious adverse event occurring from acupuncture therapy is the same as taking penicillin. The safety of acupuncture is a serious concern, particularly in pediatrics. Because acupuncture's mechanism is not known, the use of needles in children becomes questionable. For example, acupoints on the vertex of infants should not be needled when the fontanel is not closed. It is also advisable to apply few needles or delay treatment to the children who have overeaten, are overfatigued, or are very weak. Through our review of pediatric adverse events, we found a 1.55 risk of adverse events occurring in 100 treatments of acupuncture that coincides with the low risk detailed in the studies mentioned previously. The actual risk to an individual patient is hard to determine because certain patients, such as an immunosuppressed patient, can be predisposed to an increased risk, acupuncturist's qualifications differ, and practices vary in certain parts of the world. Nevertheless, it seems acupuncture is a safe complementary/alternative medicine modality for pediatric patients on the basis of the data we reviewed.