In-country availability of medical abortion medicines: a description of the framework and methodology of the WHO landscape assessments

The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO’s latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women’s experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: (1) develop and optimise a strategy for implementing the LCG (formative phase); and (2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase). In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women’s experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness. Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally. Trial registration: CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022). The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women’s and newborn’s health outcomes, and women’s experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.     

Measuring the quality of skin cancer management in primary care: A scoping review

Skin cancer is a growing global problem and a significant health and economic burden. Despite the practical necessity for skin cancer to be managed in primary care settings, little is known about how quality of care is or should be measured in this setting. This scoping review aimed to capture the breadth and range of contemporary evidence related to the measurement of quality in skin cancer management in primary care settings. Six databases were searched for relevant texts reporting on quality measurement in primary care skin cancer management. Data from 46 texts published since 2011 were extracted, and quality measures were catalogued according to the three domains of the Donabedian model of healthcare quality (structure, process and outcome). Quality measures within each domain were inductively analysed into 13 key emergent groups. These represented what were deemed to be the most relevant components of skin cancer management as related to structure, process or outcomes measurement. Four groups related to the structural elements of care provision (e.g. diagnostic tools and equipment), five related to the process of care delivery (e.g. diagnostic processes) and four related to the outcomes of care (e.g. poor treatment outcomes). A broad range of quality measures have been documented, based predominantly on articles using retrospective cohort designs; systematic reviews and randomised controlled trials were limited.     

Preliminary evidence supporting a new enzymatic debridement product for use in chronic wounds

A new recombinant proteolytic enzyme, isolated from maggot saliva, with fibrinolytic action has been investigated through a series of non-clinical toxicology and in-vitro/in-vivo pharmacology studies to explore its potential safety and efficacy as an enzymatic debridement agent for use in chronic wounds. Studies indicate that the enzyme has a good safety profile. When locally administered, it is not detrimental to wound healing, is non-sensitising and is rapidly inactivated in the systemic circulation. Adverse effects are limited, at very high concentrations, to transient erythema at the site of application. In-vitro testing indicates that the enzyme, whilst selective for fibrin, has additional proteolytic action against collagen and elastin, with enzymatic action for all three substrates being dose dependent. In-vivo, we used an established MRSA biofilm model, in which microbiological counts were used as a surrogate for debridement efficacy. Here, we showed that higher concentrations of the enzyme in a formulated proprietary gel, significantly reduced MRSA counts over a period of 2 to 14 days, and significantly improved the vascularity of the wound at 14 days. Together, these data support the potential for this maggot-derived proteolytic enzyme as a clinically effective debriding agent.     

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study

ObjectivesTo develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases.Materials and methodsA review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer.ResultsLimited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic.ConclusionsThe international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.     

Aromatase expression in the eutopic endometrium of myomatous uteri: The influence of the menstrual cycle and oral contraceptive use

Aims. To detect aromatase expression in the endometrium of myomatous uteri and to correlate it with the location of the myoma, phase of the menstrual cycle, the presence of menorrhagia and oral contraceptive use.

Method. Aromatase p450 expression was measured using immunohistochemical methods in the endometrium of 116 patients. Sixty-one patients had menorrhagia associated with intramural/submucous myomas and nine had subserous myomas and no excessive bleeding. Forty-six patients had no uterine pathology and served as controls. Nineteen out of 61 patients with menorrhagia were oral contraceptive users at the time of the examination. Endometrial samples were obtained by hysteroscopy in all cases.

Results. Aromatase p450 expression was detected more frequently in the eutopic endometrium of patients with submucous or intramural myomas than in those in the subserous group, and was significantly greater during the proliferative phase than during the luteal phase or following the use of oral contraceptives. In normal uteri, aromatase expression was detected in the endometrium in less than 10% of users.

Conclusions. Aromatase expression in the endometrium was affected by the location of the myoma, the presence of symptoms, and the phase of the menstrual cycle. Oral contraceptives, on the other hand, inhibited aromatase expression in the eutopic endometrium of patients with submucous/intramural myomas.     

In Vitro Effects of Tp5 Analogs on E-Rosette Formation and Cell Division

The effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests.

Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg-Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides.

Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED₇₅) inhibited E-receptor. Treatment of azathioprine (ED₇₅-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC.

Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED₃₀. These “suppressive” peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours.

Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor. Arginine, lysine, and acidic aspartyl residue seem to be a necessary basic structure to produce a cumulative chemical signal on the activity of T-lymphocytes.     

L-carnitine ameliorates gentamicin-induced renal injury in rats.

BACKGROUND: This study examined whether administration of L-carnitine ameliorates gentamicin-induced renal injury in rats. METHODS: Male Sprague-Dawley rats were assigned to one of seven treatment groups: group A (control) rats were given normal saline injections daily for 8 consecutive days; group B, C and D rats were given gentamicin injections, 50 mg/kg body weight/day daily for 8 consecutive days; and group E, F and G rats were given gentamicin injections, 80 mg/kg/day daily for 8 consecutive days. Starting 4 days before these injections, all groups were given additional injections, for 12 consecutive days, of normal saline (groups A, B and E) or L-carnitine at 40 mg/kg (groups C and F) or 200 mg/kg (groups D and G). Histological scoring of renal cortical pathology was performed after day 12. RESULTS: Among rats injected with gentamicin 50 mg/kg/day, those given either 40 or 200 mg/kg/day of L-carnitine had higher creatinine clearances at day 12 than the rats not given carnitine. In the rats given 80 mg/kg gentamicin and no carnitine, renal function tended to be lower than in controls. At day 12, the rats given gentamicin 80 mg/kg and L-carnitine 200 mg/kg/day, compared with rats given gentamicin 80 mg/kg and no carnitine, displayed lower serum urea and probably creatinine concentrations, and higher creatinine clearances, and their serum urea was not different from control (group A) rats. Both doses of gentamicin induced renal cortical histopathology. Changes were milder with gentamicin 50 mg/kg/day, and L-carnitine, particularly at 200 mg/kg/day, ameliorated the severity of renal pathology induced by both gentamicin doses. In rats given gentamicin 80 mg/kg/day, the animals treated with carnitine 200 mg/kg/day had significantly less severe proximal tubular necrosis and significantly greater mild proximal tubular necrosis compared with rats receiving L-carnitine 40 mg/kg/day or no carnitine. CONCLUSIONS: In rats receiving gentamicin, daily L-carnitine injections, particularly at 200 mg/kg/day, ameliorate the severity of renal cortical proximal tubular necrosis and maintain greater renal function.     

Rectal endosonography in inflammatory bowel disease: differential diagnosis and prediction of remission

BACKGROUND AND STUDY AIMS: There are few and conflicting data on EUS features of the rectal wall in Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to determine whether rectal EUS could first differentiate between CD and UC, and secondly predict remission in CD. PATIENTS AND METHODS: During a 14 month period we prospectively and blindly studied several parameters on rectal EUS (total wall thickness, mucosal appearance, submucosal thickness, number of enlarged vessels in the submucosa and number of pathological lymph nodes around the rectum and sigmoid colon) in 20 normal subjects, 26 patients with UC, 39 patients with CD, and four with infectious colitis. Comparisons were made between normal controls, patients with acute UC and those with acute CD, as well as between acute flare-ups and quiescent forms of CD and UC in the same patients. RESULTS: Normal subjects showed some features which were significantly different from those in CD or UC patients. A greater number of pathological lymph nodes was characteristic for acute UC, whereas the number of enlarged vessels was increased in acute CD. Quiescent CD showed a lower amount of wall thickening than acute CD. No significant alterations of the five parameters were found in quiescent UC compared to acute UC. CONCLUSIONS: This study suggests that EUS could be helpful in differentiating acute UC from CD, and to predict remission in CD.     

Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy

Oxygen-induced retinopathy (OIR) in the mouse, like the analogous human disease retinopathy of prematurity, is an ischemic retinopathy dependent on oxygen-induced vascular obliteration. We tested the hypothesis that chemically overriding the oxygen-induced downregulation of hypoxia-inducible factor (HIF) activity would prevent vascular obliteration and subsequent pathologic neovascularization in the OIR model. Because the degradation of HIF-1α is regulated by prolyl hydroxylases, we examined the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in the OIR model. Our results determine that stabilizing HIF activity in the early phase of OIR prevents the oxygen-induced central vessel loss and subsequent vascular tortuosity and tufting that is characteristic of OIR. Overall, these findings imply that simulating hypoxia chemically by stabilizing HIF activity during the causative ischemia phase (hyperoxia) of retinopathy of prematurity may be of therapeutic value in preventing progression to the proliferative stage of the disease.     

Blood donors’ positivity for transfusion-transmissible infections: the Serbian Military Medical Academy experience

Background

Members of armed forces worldwide are considered to be very susceptible to sexually transmitted infections, thus falling into a high-risk group of blood donors regarding transfusion-transmissible infections. In the Serbian Military Medical Academy a significant number (44% for the period 2005–2013) of blood donations were from members of the Serbian Army. The aim of this study was to determine the significance of military blood donors for the safety of blood transfusion.

Material and methods

Between January 2005 and December 2013, a total of 155,479 blood donations were tested for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis using serological assays (enzyme immunoassays, chemiluminescent microparticle immunoassay and western blot) and molecular testing (polymerase chain reaction analysis).

Results

The percentage of blood donations positive for transfusion-transmissible infections in the estimated period was 0.38%, and the percentage of HBV, HCV, HIV and syphilis positive blood donations was 0.20%, 0.12%, 0.005% and 0.06%, respectively. During that period, the percentage of all transfusion-transmissible infections, and in particular of HBV and HCV, declined significantly. In contrast, the percentage of HIV and syphilis positive blood donations remained unchanged. Higher rates of positivity for transfusion-transmissible infections in blood donations from members of the Serbian Army were not found, especially after mandatory military service was abolished in 2009.

Discussion

The reported rate of positivity for transfusion-transmissible infections in blood donations from the Military Medical Academy was considered low. This information is of great significance for further implementation of public health measures.