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1.  Pelvic inflammatory disease 
Clinical Evidence  2008;2008:1606.
Introduction
Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the USA and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment compared with treatment delayed until the results of microbiological investigations are known? How do different antimicrobial regimens compare? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 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 nine 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: antibiotics (oral, parenteral, empirical treatment, treatment guided by test results, different durations, outpatient, inpatient), and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).
Key Points
Pelvic inflammatory disease (PID) is caused by infection of the upper female genital tract, and is often asymptomatic. PID is the most common gynaecological reason for admission to hospital in the USA, and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.Epithelial damage from infections such as Chlamydia trachomatis or Neisseria gonorrhoeae can allow opportunistic infection from many other bacteria.About 20% of women with PID become infertile, 40% develop chronic pain, and 1% of women who conceive have an ectopic pregnancy.Spontaneous resolution of symptoms may occur in some women, but early initiation of treatment is needed to prevent impairment of fertility.
As there are no reliable signs and symptoms of PID, empirical treatment is common. The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by 3 days can impair fertility.The absence of infection from the lower genital tract does not exclude a diagnosis of PID.
Oral antibiotics are likely to be beneficial, and are associated with the resolution of symptoms and signs of pelvic infection, but we don't know which antibiotic regimen is best. Clinical and microbiological cure rates of 88% to 100% have been reported after oral antibiotic treatment.The risks of tubal occlusion and infertility depend on severity of infection before treatment. Clinical improvement may not necessarily translate into improved fertility.
Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment is as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration of treatment.
Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but we don't know whether prophylactic antibiotics before IUD insertion reduce these risks.
PMCID: PMC2907941  PMID: 19450319
2.  How well is pelvic inflammatory disease managed in general practice? A postal questionnaire survey 
Sexually Transmitted Infections  1998;74(5):361-363.
OBJECTIVE: Many patients with pelvic inflammatory disease (PID) present to their general practitioners. Chlamydia trachomatis is the organism most commonly implicated in this condition. This study aims to examine how well PID is managed in the primary care setting and highlight areas for improvement. METHODS: The study was performed by sending postal questionnaires to 180 randomly selected general practitioners in Birmingham. Given the example of a woman presenting clinically with PID, the doctors were asked questions on diagnosis and treatment. To assess factors that may influence the answers, they were also asked about their sex, year of qualification, and postgraduate training. RESULTS: 139 questionnaires (77%) were returned. 91.4% of the respondents feel confident in managing patients with PID, and only 9.3% would usually refer these patients on. However, 54.7% do not perform an endocervical swab for C trachomatis, 37.4% do not include anti-chlamydial antibiotics in their treatment regimen, and 24.5% do not advise sexual partners to be screened. Female doctors, those with higher degrees, or obstetrics and gynaecology experience were more likely to give anti-chlamydial therapy, but no factors of the respondents significantly influenced contact tracing behaviour. CONCLUSIONS: The management of a patient presenting with PID should include investigation for C trachomatis and treatment with an appropriate antibiotic. As PID is often a sexually transmitted disease, contact tracing of sexual partners should be undertaken. The study suggests that a significant proportion of general practitioners would not have offered optimal management to patients with PID. 





PMCID: PMC1758144  PMID: 10195033
3.  Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study 
BMC Infectious Diseases  2012;12:187.
Background
Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia) might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection.
Methods
We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT) and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT.
Results
The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13%) in both processes.
Conclusions
The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.
doi:10.1186/1471-2334-12-187
PMCID: PMC3505463  PMID: 22883325
Chlamydia infection; Pelvic inflammatory disease; Mathematical model; Compartmental model; Randomised controlled trials
4.  Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies 
The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing.
doi:10.1186/1476-7961-9-6
PMCID: PMC3080807  PMID: 21477322
5.  Chlamydia (uncomplicated, genital) 
Clinical Evidence  2010;2010:1607.
Introduction
Genital chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in developed countries. In women, infection occurs most commonly between the ages of 16 and 19 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antibiotic treatment for men and non-pregnant women with uncomplicated genital chlamydial infection?What are the effects of antibiotic treatment for pregnant women with uncomplicated genital chlamydial infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (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 24 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: amoxicillin, ampicillin, azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin, lymecycline, minocycline, ofloxacin, pivampicillin, rifampicin, roxithromycin, sparfloxacin, tetracycline, and trovafloxacin.
Key Points
Genital chlamydia (Chlamydia trachomatis serotypes D–K) is a sexually transmitted infection (STI) that infects the urethra in men and the endocervix or urethra (or both) in women. It is defined as uncomplicated if it has not ascended to the upper genital tract or caused sexually acquired reactive arthritis. It is the most common bacterial STI in developed countries. Over 200,000 chlamydia diagnoses were made in the UK in 2008, with 60% of cases being detected in departments of genitourinary medicine.Infection is usually asymptomatic, particularly in women. Most people infected do not present for testing or treatment. Therefore, population rates based on routine surveillance data underestimate the true disease burden. One in 14 men and one in 11 women aged under 25 years screened as part of the National Chlamydia Screening Programme in the UK tested positive for chlamydia. If untreated, chlamydial infection can ascend to the upper genital tract, causing pelvic inflammatory disease (PID), which may result in infertility, ectopic pregnancy, or chronic pelvic pain.Partner notification and treatment is an important part of effective management.Chlamydia-positive individuals are at high risk of retesting positive within 1 year. There is a growing body of opinion that repeat testing at 3 to 12 months after treatment, or sooner if there is a change of sexual partner, is likely to be beneficial for public health.
Multiple-dose regimens of tetracyclines (doxycycline or tetracycline) achieve microbiological cure in at least 95% of men and non-pregnant women with genital chlamydia. Erythromycin also seems beneficial as a multiple-dose regimen, but we don't know which regimen of erythromycin is more effective. Ciprofloxacin seems less likely to lead to microbiological cure compared with doxycycline.We don't know whether multiple-dose regimens of other antibiotics (such as other macrolides, quinolones, and penicillins) are effective, as we found few adequate studies.
A single dose of azithromycin seems as beneficial as a 7-day course of doxycycline, and produces similar rates of adverse effects. Single-dose treatments have the obvious advantage of improving adherence.Treatment cure rates of over 95% have been reported, and a test of cure is only considered necessary if non-compliance or re-exposure is suspected.
In pregnant women, multiple-dose regimens of erythromycin or amoxicillin seem effective in treating chlamydial infection. One small study has also suggested that clindamycin and multiple-dose erythromycin are equally effective at curing infection, although the size of the study makes it hard to draw definitive conclusions.
Single-dose azithromycin may be effective in treating chlamydia in pregnant women. However, it should be used only if no adequate alternative is available.
In pregnant women, no antibiotic regimen has a microbiological cure rate of over 95%, and pregnant women should be offered a test of cure no sooner than 5 weeks after treatment was initiated to ensure that the infection has cleared.
PMCID: PMC2907609  PMID: 21718568
6.  Management of first-episode pelvic inflammatory disease in primary care: results from a large UK primary care database 
The British Journal of General Practice  2010;60(579):e395-e406.
Background
Prompt and effective treatment of pelvic inflammatory disease (PID) may help prevent long-term complications. Many PID cases are seen in primary care but it is not known how well management follows recommended guidelines.
Aim
To estimate the incidence of first-episode PID cases seen in UK general practice, describe their management, and assess its adequacy in relation to existing guidelines.
Design of study
Cohort study.
Setting
UK general practices contributing to the General Practice Research Database (GPRD).
Method
Women aged 15 to 40 years, consulting with a first episode of PID occurring between 30 June 2003 and 30 June 2008 were identified, based on the presence of a diagnostic code. The records within 28 days either side of the diagnosis date were analysed to describe management.
Results
A total of 3797 women with a first-ever coded diagnosis of PID were identified. Incidence fell during the study period from 19.3 to 8.9/10 000 person-years. Thirty-four per cent of cases had evidence of care elsewhere, while 2064 (56%) appeared to have been managed wholly within the practice. Of these 2064 women, 34% received recommended treatment including metronidazole, and 54% had had a Chlamydia trachomatis test, but only 16% received both. Management was more likely to follow guidelines in women in their 20s, and later in the study period.
Conclusion
These analyses suggest that the management of PID in UK primary care, although improving, does not follow recommended guidelines for the majority of women. Further research is needed to understand the delivery of care in general practice and the coding of such complex syndromic conditions.
doi:10.3399/bjgp10X532404
PMCID: PMC2944949  PMID: 20883614
chlamydia; electronic health records; incidence; pelvic inflammatory disease; primary health care
7.  The clinical diagnosis of pelvic inflammatory disease – reuse of electronic medical record data from 189 patients visiting a Swedish university hospital emergency department 
BMC Women's Health  2006;6:16.
Background
The pelvic inflammatory disease (PID) diagnosis is mostly based on clinical findings. However, few studies have examined the clinical basis for the diagnostics of PID, which was the aim of this study.
Methods
A retrospective study was performed of 189 out-patients diagnosed as having PID at the obstetric and gynecological emergency department of a Swedish university hospital. Data on symptoms, signs, pelvic examination and laboratory tests were extracted from the electronic medical records in comparison with the diagnostic criteria of the PID Guideline of the US Center of Disease Control from 2002 (CDC 2002 Guidelines).
Results
Eight symptoms in varying combinations were associated with the PID diagnosis. Most of them are mentioned in the CDC 2002 Guidelines. Detected rates of C. Trachomatis (CT) and N. Gonorrhoeae (NG) were 5% and 0%, respectively, among the tested patients (CT = 52% and NG = 12%). The C-reactive protein was normal in the majority of tested patients.
Conclusion
The clinical basis for the diagnostics of PID was largely in accordance with the criteria in the CDC 2002 Guidelines. The limited number of CT tests performed is somewhat disappointing, considering the fact that effective disease prevention includes widespread CT screening. Further studies in different settings are needed in order to analyze how the testing rate for CT can be improved in clinical praxis.
doi:10.1186/1472-6874-6-16
PMCID: PMC1624808  PMID: 17054801
8.  National Trends in Pelvic Inflammatory Disease among Adolescents in the Emergency Department 
Objective
In 2002 the CDC broadened the pelvic inflammatory disease (PID) diagnostic criteria to increase detection and prevent serious sequelae of untreated PID. The impact of this change on PID detection is unknown. Our objective was to estimate trends in PID diagnosis among adolescent emergency department (ED) patients before and after the revised CDC definition and identify factors associated with PID diagnoses.
Methods
We performed a retrospective repeated cross-sectional study using the National Hospital Ambulatory Medical Care Survey from 2000–2009 of ED visits by 14 to 21 year old females. National estimates of PID rates were calculated. Multivariable logistic regression analyses and tests of trends were performed.
Results
During 2000–2009, of the 77 million female adolescent ED visits, there were an estimated 704,882 (95% CI 571,807, 837,957) cases of PID. Following the revised criteria, PID diagnosis declined from 5.4 cases per 1000 U.S. adolescent females to 3.9 cases per 1000 (p=0.03). In a multivariable model, age ≥17 years (OR 2.14, 95% CI 1.25, 3.64) and Black race (OR 2.04, 95% CI 1.36, 3.07) were associated with PID diagnosis
Conclusions
Despite broadened CDC diagnostic criteria, PID diagnoses did not increase over time. This raises concern about awareness and incorporation of the new guidelines into clinical practice.
doi:10.1016/j.jadohealth.2013.03.016
PMCID: PMC3725218  PMID: 23743002
Pelvic inflammatory disease; Adolescents; Trends
9.  Bacterial Isolates Associated With Pelvic Inflammatory Disease Among Female Patients Attending Some Hospitals in Abuja, Nigeria 
Background
Pelvic inflammatory disease refers to any infection in the female lower reproductive tract that spreads to the upper reproductive tract. The disease comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess and pelvic peritonitis. PID is not a notifiable disease in most countries, so accurate statistics are not available. This situation is not in any way different here in Nigeria and more so in the Federal Capital Territory, Abuja where this research was conducted, there had never been any published report so far on PID. It therefore became pertinent that such studies be carried out to evaluate the bacterial organisms which may be associated with the disease in this part of Nigeria so that health care providers could take a better look at this affliction in women.
Materials and Methods
Endocervical swabs totalling 100 were aseptically collected from patients with confirmed Pelvic Inflammatory Disease (PID), attending some hospitals in Abuja, Nigeria for detection of bacterial pathogens based on cultural and biochemical characterisation tests. Antibiogram was also conducted on the identified bacterial isolates.
Results
Out of the 100 samples analysed, 43% yielded pure cultures of bacterial isolates, 2% yielded mixed cultures while no bacterial growths were recorded from the remaining 55% samples. Organisms encountered were Staphylococcus aureus (16%), Escherichia coli (10%), Streptococcus faecalis (8%), Pseudomonas aeruginosa (4%), Streptococcus pyogenes (3%), Klebsiella pneumoniae (3%), Proteus rettgeri (2%) and Proteus mirabilis (1%). The highest percentage occurrence of pathogenic isolates was observed in polygamous married patients (90%). The age group most affected falls within the mean age 30.5 years (68%) while the least affected group falls within the mean age 40.5 years (5%). There was a significant difference in the acquisition of PID in relation to marital status (P < 0.05). However there was no significant difference in the acquisition of the disease with respect to age (P > 0.05). Antibiogram patterns of pathogenic isolates revealed varied resistance to most of the antibiotics employed. Cefotaxime (a new generation cephalosporin antibiotic) was established in this study as the best antimicrobial agent for treatment of PID due to Gram-positive and Gram-negative bacteria isolated from the women examined.
Conclusion
In conclusion, Pelvic inflammatory disease is a major health problem in developed or developing countries of the world. PID is not a notifiable disease, as accurate statistics on disease prevalence are rarely available. There is therefore no doubt thousands of young women have salpingitis every year and their sheer number makes it an important health problem. PID hence can be said to be a very serious complication of sexually transmitted disease which should be critically and promptly handled by healthcare providers. The right type sample should be aseptically collected and be appropriately handled for laboratory investigation. Treatment of PID should be initiated as soon as the presumptive diagnosis has been made. Immediate administration of antibiotics has been effective in the long-term sequelae associated with PID, especially new generation antibiotics, such as cefotaxime as recorded in this study.
PMCID: PMC3957208  PMID: 24653811
Bacterial isolates; Pelvic inflammatory disease; Female patients
10.  Doxycycline or Ofloxacin for Outpatient Chlamydial Pelvic Inflammatory Disease? A Cost-Benefit and Cost-Effectiveness Analysis 
Objective: The current Centers for Disease Control and Prevention (CDC) guidelines include 2 drugs, doxycycline and ofloxacin, for treatment of the chlamydial component of outpatient pelvic inflammatory disease (PID). Although ofloxacin costs about $90 more than doxycycline, doxycycline is frequently associated with side effects and patient compliance with this drug is probably poor. Because clinicians have little information by which to judge the tradeoffs between price and compliance for these 2 antibiotics, we examined the impact of patient compliance in the evaluation of the costs and benefits of using each drug.
Methods: The incidence and direct costs of PID sequelae (infertility, ectopic pregnancy, and chronic pelvic pain) resulting after partially treated chlamydial PID were taken from previous estimates. For differing levels of antibiotic compliance, the probability of cure, probability of the occurrence of sequelae, and the associated cost of each were calculated. Because the relationship between partial antibiotic compliance and PID cure is unknown, we included 3 plausible relationships in our analyses. The sensitivity analysis was performed by varying key assumptions and examining the effect of each on future costs.
Results: The average probability of future PID sequelae attributable to chlamydia is slightly less than 2%, with an associated cost of $1,272. With an average compliance for doxycycline of 50%, an improvement in compliance of as little as 1.8–3.5 percentage points (51.8–53.5%), depending on the assumption used regarding partial compliance and cure, would make the use of ofloxacin less costly than doxycycline in the long run. Even with a cost difference of $90 between the 2 drugs, a 10-percentage-point increase in compliance (to 60% compliance) with the more expensive drug would save $2.63 for each $1.00 spent.
Conclusions: Since the long-term costs of PID are likely to overshadow the immediate cost of providing treatment, physicians should carefully consider the likelihood of patient compliance in selecting an antibiotic.
doi:10.1155/S106474499500024X
PMCID: PMC2364411  PMID: 18475415
11.  The effectiveness of nonsteroidal anti-inflammatory agents in the treatment of pelvic inflammatory disease: a systematic review 
Systematic Reviews  2014;3:79.
Background
Pelvic inflammatory disease (PID) is the result of infection ascending through the endocervix to the uterus and fallopian tubes. Inflammation driven by infected host cells appears to be central to the development of tissue damage and associated reproductive complications. Nonsteroidal anti-inflammatory agents (NSAIDs) therefore have the potential to reduce the sequelae associated with pelvic infection.
Methods
A search of four electronic reference databases, an internet search for relevant grey literature and a review of the bibliographies of identified publications was used to identify studies evaluating NSAIDs in the management of PID. A predefined search strategy was used to identify studies that included women with PID aged over 16 and diagnosed after 1980. Randomized controlled trials, nonrandomized controlled trials, and cohort studies with comparison group data were included without language restriction. Two reviewers independently assessed the studies against agreed criteria and extracted relevant data using a standardized pro forma. A meta-analysis to calculate the relative risk associated with NSAID use was planned if appropriate.
Results
Forty-three studies were identified. After reviewing abstracts or full texts, two randomized controlled trials were found to meet the selection criteria for inclusion. The use of NSAIDs was reported to improve tubal patency, reduce pelvic adhesions and reduce suprapubic pain but the studies were of poor quality with a high risk of bias. Meta-analysis of the data was not performed.
Conclusions
Insufficient data is available to support or refute the efficacy of NSAIDs in the prevention of short or long-term complications of PID.
doi:10.1186/2046-4053-3-79
PMCID: PMC4125595  PMID: 25052765
nonsteroidal anti-inflammatory drugs; pelvic inflammatory disease; systematic review
12.  Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease 
Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID). Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.
doi:10.1155/2011/959816
PMCID: PMC3253449  PMID: 22235165
13.  Risk factors associated with pelvic inflammatory disease 
Sexually Transmitted Infections  2006;82(6):452-457.
Objective
To investigate factors associated with pelvic inflammatory disease (PID).
Methods
A case–control study was used to investigate demographic and behavioural factors, and causative agents associated with PID.
Results
A total of 381 participants were recruited: 140 patients, and 105 and 136 controls in tubal ligation and general practice groups, respectively. When compared with a PID‐free tubal ligation control group, increased risk of PID was associated with: age <25 years; age at first sexual intercourse <20 years; non‐white ethnicity; not having had children; a self‐reported history of a sexually transmitted disease; and exposure to Chlamydia trachomatis. When compared with a general practice control group, increased risk was associated with: age <25 years; age at first sexual intercourse <15 years; lower socioeconomic status; being single; adverse pregnancy outcome; a self‐reported history of a sexually transmitted disease; and exposure to C trachomatis. Of the cases, 64% were not associated with any of the infectious agents measured in this study (idiopathic).
Conclusions
A high proportion of cases were idiopathic. PID control strategies, which currently focus on chlamydial screening, have to be reviewed so that they can prevent all cases of PID. Behavioural change is a key factor in the primary prevention of PID, and potential modifiable risk factors were associated with PID.
doi:10.1136/sti.2005.019539
PMCID: PMC2563866  PMID: 16901918
14.  Epidemiology and Clinical Outcome of Patients Hospitalized With Pelvic Inflammatory Disease Complicated by Tubo-Ovarian Abscess 
Objective: The purpose of this retrospective study was to compare the clinical outcome and characteristics of pelvic inflammatory disease (PID) complicated by tubo-ovarian abscess (TOA) with PID without TOA.
Methods: Chart reviews were performed for all PID admissions to the University of Medicine and Dentistry of New Jersey-University Hospital, Newark, NJ, from January 1, 1992, to December 31, 1993.
Results: The incidence in this study of TOA based on sonographic evidence of a complex adnexal mass was 18%. The major differences between the patients with and without TOAs were 1) history of hospitalization for PID: 68% (13/19) vs. 29% (25/85); 2) increased erythrocyte sedimentation rate: 82 vs. 41 mm/h; 3) increased WBC count on admission: 16,200 vs. 14,700/ml; 4) failure to respond to initial antibiotic therapy; and 5) longer hospital stay: 7.8 vs. 4.4 days, respectively. Surgical intervention was required in 3 patients: 2 patients who had TOAs and 1 patient who did not have a TOA by clinical examination or by ultrasound.
Conclusions: Despite longer hospital stays and blood tests suggesting more severe disease processes, PID complicated by TOA is usually responsive to intravenous (IV) antibiotic therapy without the need for surgical intervention.
doi:10.1155/S1064744995000470
PMCID: PMC2364435  PMID: 18476036
15.  Pelvic Inflammatory Disease: A Family Practice Perspective 
Canadian Family Physician  1989;35:1309-1314.
Most women with symptomatic acute pelvic inflammatory disease (PID) are now managed outside of hospital by private practitioners. Clinical diagnosis of PID is often inaccurate, but can be improved by knowledge of risk factors, use of simple investigations, and referral for laparoscopy when the physician is unsure. Prompt treatment with a recommended regimen that includes at least two antibiotics, careful consideration of when to hospitalize or refer, and an awareness of the need for compliance and follow up are important attributes of good management. In contrast, asymptomatic PID, which is a common antecedent of tubal factor infertility and ectopic pregnancy, can be prevented only by screening for and appropriate treatment of sexually transmitted infections.
Images
PMCID: PMC2280404  PMID: 21248967
C-reactive protein; Chlamydia trachomatis; erythrocyte sedimentation rate; pelvic inflammatory disease; sexually transmitted disease
16.  Primary immunodeficiency 
Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders.
doi:10.1186/1710-1492-7-S1-S11
PMCID: PMC3245434  PMID: 22165913
17.  Attentiveness of pediatricians to primary immunodeficiency disorders 
BMC Research Notes  2012;5:393.
Background
Primary immunodeficiency (PID) is a cluster of serious disorders that requires special alertness on the part of the medical staff for prompt diagnosis and management of the patient. This study explored PID knowledge and experience among pediatricians of wide educational backgrounds, practicing in the United Arab Emirates (UAE).
Method
A self-administered questionnaire was used to determine the competency of pediatricians in their knowledge of PID disorders. This study questionnaire included questions on PID signs and symptoms, syndromes associated with immunodeficiency, screening tests, interpreting laboratory tests and case management. The participants were 263 pediatricians of diverse education working in the 27 governmental hospitals in all regions of UAE.
Results
The overall performance of the pediatricians did not differ based on their age, gender, origin of certification, rank, or years of experience. Of the 50 questions, 20% of pediatricians answered correctly <60% of the questions, 76% answered correctly 60 to 79% of the questions, and 4% answered correctly ≥80% of the questions. Seventeen of the 19 PID signs and symptoms were identified by 55 to 97%. Four of 5 syndromes associated with immunodeficiency were identified by 50 to 90%. Appropriate screening tests were chosen by 64 to 96%. Attention to the laboratory reference range values as function of patient age was notably limited.
Conclusions
There was a noteworthy deficiency in PID work-up. Therefore, implementing effective educational strategies is needed to improve the competency of pediatricians to diagnose and manage PID disorders.
doi:10.1186/1756-0500-5-393
PMCID: PMC3475124  PMID: 22846098
Survey; Primary immunodeficiency; Knowledge; Diagnosis; Management
18.  Epidemiology of ectopic pregnancy during a 28 year period and the role of pelvic inflammatory disease 
Objectives: We analysed the epidemiology of ectopic pregnancy (EP) during a 28 year period, 1970–97, using methods applicable to ecological studies in order to test the hypothesis that a reduction of pelvic inflammatory disease (PID) will be associated with a decrease of EP.
Methods: Hospital records of patients aged 15–54 admitted to our department of gynaecology were reviewed for EP and PID for the period 1 January 1970 to 31 December 1997. EP for the period 1970–4 was based on available statistics. The total number for EP was 1270 and for PID 2559. The total population for the catchment area was 100 000–120 000 during the study period. Incidences were age standardised and calculated using official population statistics to represent the average female population in the five 5 year periods 1970–4, 1975–9, 1980–4, 1985–9, 1990–4, and in each of the consecutive years 1995, 1996, and 1997. Incidences for EP were calculated per 1000 women and per 1000 pregnancies while those for PID per 1000 women. National statistical data of EP were available for 1975–94 and were used for comparison with the local study.
Results: The EP incidences increased from 7.7 per 1000 pregnancies in the first 5 year period to 13.4 in the second, and continued to rise for another decade reaching the peak figures of 16.6 in 1985–9—that is, more than a twofold increase. Since then and to 1997 the EP incidence has decreased by 30%. PID admissions increased during the study period from 2.7 per 1000 women in the first 5 year period to 3.2 in the second. From then on they continuously decreased and reached a low of 0.5 in 1997. The greatest changes occurred in women ≤24 years of age. The peak incidence for this age group was 7.7 in 1975–9, and the lowest was 0.4 per 1000 women in 1996. The greatest reduction of EPs was noted for women ≤24 years old, from a high of 10.0 in 1975–9, coinciding with the peak incidence of PID, to a low of 4.0 in 1997, a reduction of 58.4%. The incidence of EP was two to three times higher in women ≥25 years old, most obvious in those ≥30 years, with peak figures of 20.9 per 1000 pregnancies in 1985–9, and 13.9 in 1997, a reduction of 33.4% and the lowest figures for the past 23 years. For women aged 25–29 years the incidence peaked in the previous 5 year period 1980–4—that is, one 5 year period later than for those ≤24 years, which we interpret as cohort effects in relation to PID.
Conclusions: Reduction of PID was strongly associated with a decline of EP. The decline was greater and immediate for women ≤24 years old, than for those ≥25 years. The two to three times higher EP incidence in women ≥25 years of age was most probably due to a cohort effect as the peak of PID occurred a decade earlier in women ≤24 years old. Prevention of PID may not only reduce EP but also reduce adverse effects on tubal patency.
Key Words: ectopic pregnancy; pelvic inflammatory disease; gonorrhoea; Chlamydia trachomatis, sexually transmitted disease; Sweden
doi:10.1136/sti.76.1.28
PMCID: PMC1760576  PMID: 10817065
19.  Improvement in the clinical cure rate of outpatient management of pelvic inflammatory disease following a change in therapy 
Sexually Transmitted Infections  2005;81(3):233-235.
Objective: In the United Kingdom many genitourinary medicine clinics use oral doxycycline and metronidazole to treat pelvic inflammatory disease (PID). A retrospective case note review of PID treatment at our department in 2000 showed that the clinical cure rate (CCR) was only 55% with oral doxycycline and metronidazole for 2 weeks. We therefore added ceftriaxone 250 mg intramuscularly to the doxycycline and metronidazole for treating PID. We have repeated the review and compared the results with those from 2000.
Methods: All patients diagnosed as having PID between 1 July 2002 and 31 December 2002 were identified. These episodes were diagnosed on clinical presentations of pelvic pain, vaginal discharge or bleeding, and cervical motion tenderness on physical examination. The CCR was defined as patients who fully resolved their symptoms and signs during 2 week and 4 week follow up. The results were compared with those from 2000.
Results: Women receiving ceftriaxone, doxycycline, and metronidazole had a CCR of 72%. In 2000 the CCR for women receiving only doxycycline and metronidazole was 55%. There were only 8% non-responders in 2002 compared with 18% in 2000. Comparing CCR and non-response rate, in 2002 there was a significant improvement in cure rate, OR 3.01 (95% CI 1.28 to 7.47) p = 0.009. Using an intent to treat analysis and including the defaulters as treatment failures there was still a significant improvement in cure rate, OR 2.03 (95% CI 1.18 to 3.50) p = 0.009.
Conclusions: The treatment of PID with ceftriaxone, doxycycline, and metronidazole gave a significantly higher CCR than doxycycline and metronidazole. Our experience would suggest that doxycycline and metronidazole alone is not a suitable regimen for treatment of PID in the United Kingdom.
doi:10.1136/sti.2004.012377
PMCID: PMC1744974  PMID: 15923292
20.  Improving the recruitment activity of clinicians in randomised controlled trials: a systematic review 
BMJ Open  2012;2(1):e000496.
Background
Poor recruitment to randomised controlled trials (RCTs) is a widespread problem. Provision of interventions aimed at supporting or incentivising clinicians may improve recruitment to RCTs.
Objectives
To quantify the effects of strategies aimed at improving the recruitment activity of clinicians in RCTs, complemented with a synthesis of qualitative evidence related to clinicians' attitudes towards recruiting to RCTs.
Data sources
A systematic review of English and non-English articles identified from: The Cochrane Library, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ebsco CINAHL, Index to Theses and Open SIGLE from 2001 to March 2011. Additional reports were identified through citation searches of included articles.
Study eligibility criteria
Quantitative studies were included if they evaluated interventions aimed at improving the recruitment activity of clinicians or compared recruitment by different groups of clinicians. Information about host trial, study design, participants, interventions, outcomes and host RCT was extracted by one researcher and checked by another. Studies that met the inclusion criteria were assessed for quality using a standardised tool, the Effective Public Health Practice Project tool. Qualitative studies were included if they investigated clinicians' attitudes to recruiting patients to RCTs. All results/findings were extracted, and content analysis was carried out. Overarching themes were abstracted, followed by a metasummary analysis. Studies that met the inclusion criteria were assessed for quality using the Critical Appraisal Skills Programme qualitative checklist.
Data extraction
Data extraction was carried out by one researcher using predefined data fields, including study quality indicators, and verified by another.
Results
Eight quantitative studies were included describing four interventions and a comparison of recruiting clinicians. One study was rated as strong, one as moderate and the remaining six as weak when assessed for quality using the Effective Public Health Practice Project tool. Effective interventions included the use of qualitative research to identify and overcome barriers to recruitment, reduction of the clinical workload associated with participation in RCTs and the provision of extra training and protected research time. Eleven qualitative studies were identified, and eight themes were abstracted from the data: understanding of research, communication, perceived patient barriers, patient–clinician relationship, effect on patients, effect on clinical practice, individual benefits for clinicians and methods associated with successful recruitment. Metasummary analysis identified the most frequently reported subthemes to be: difficulty communicating trial methods, poor understanding of research and priority given to patient well-being. Overall, the qualitative studies were found to be of good quality when assessed using the Critical Appraisal Skills Programme checklist.
Conclusions
There were few high-quality trials that tested interventions to improve clinicians' recruitment activity in RCTs. The most promising intervention was the use of qualitative methods to identify and overcome barriers to clinician recruitment activity. More good quality studies of interventions are needed to add to the evidence base. The metasummary of qualitative findings identified understanding and communicating RCT methods as a key target for future interventions to improve recruitment. Reinforcement of the potential benefits, both for clinicians and for their patients, could also be a successful factor in improving recruitment. A bias was found towards investigating barriers to recruitment, so future work should also encompass a focus on successfully recruiting trials.
Article summary
Article focus
A systematic review to identify and synthesise evidence of evaluations of interventions aimed at improving clinician recruitment activity in RCTs, and evidence of clinicians' attitudes towards recruiting to RCTs.
Key messages
Evidence-based recruitment interventions aimed at supporting/incentivising clinicians are necessary for future RCTs to recruit successfully. However, evidence of successful interventions is currently limited, and interventions are being used that have limited evidential grounding. The most promising intervention identified by this review was the use of qualitative methods embedded in host RCTs to define appropriate methods, targeted at clinicians, relevant to the context of the individual studies.
The review of qualitative evidence identified a number of themes relating to clinicians' attitudes towards recruitment to RCTs. The metasummary isolated targets for future interventions aimed at improving clinicians' recruitment activity. Of particular interest were communication of trial methods, education to remove misunderstanding of trial methods and reinforcement of the potential benefits of RCTs, both for clinicians and for their patients.
Strengths and limitations of this study
Strengths
This review encompasses both quantitative and qualitative evidence regarding clinician involvement in recruiting to RCTs. As such, it highlights the available evidence, successful and unsuccessful interventions, areas of uncertainty and also targets for the design of future interventions.
Qualitative data were managed and synthesised according to a set methodology and are therefore a step beyond simple narrative review. Qualitative metasummary can be the final product of a synthesis project or used as the initial step in a metasynthesis project. The purpose of qualitative metasummary was to determine how frequently each abstracted thematic finding occurred in the included studies. Qualitative metasummary is appropriate for synthesising studies that are thematic summaries or surveys of data.
Limitations
The quality of evidence varied, and the review includes a wide range of study designs, making comparisons of interventions difficult. It is clear that RCTs of trial recruitment interventions are perceived to be difficult to carry out, so other study designs are commonly used. RCTs of recruitment interventions should be encouraged in order to increase the quality of currently available evidence.
Methodological challenges included designing a broad search to encompass qualitative and quantitative research, quality assessment of various quantitative study designs by one set of criteria and standardising the data extraction and synthesis of qualitative evidence. There are no set guidelines regarding the synthesis of qualitative and quantitative evidence, but it is clear that for many review questions limiting the included study designs would lead to empty reviews.
doi:10.1136/bmjopen-2011-000496
PMCID: PMC3253423  PMID: 22228729
21.  Clinical Predictors of Primary Immunodeficiency Diseases in Children 
Purpose
To promote awareness of primary immunodeficiency (PID), the "10 warning signs" of PID and an immunodeficiency-related (IDR) score were developed. However, their efficiency in identifying PID cases was not sufficiently evaluated in clinical practice. The objective of this study was to test the validity of the 10 warning signs and IDR score in identifying PID among children with recurrent infections at a tertiary pediatric hospital in Egypt.
Methods
A retrospective analysis of the medical records of 204 patients was performed. Of these patients, 92 had defined PID diseases and 112 were considered non-PID cases because investigations were inconclusive.
Results
Demonstrating two warning signs and an IDR score of 6 led to sensitivities of 94 and 66%, respectively, and specificities of 64 and 75%, respectively, in identifying PID cases. The strongest predictor of PID was family history that, if combined with the need for intravenous antibiotics, recurrent deep-seated infections, and failure to thrive, could identify 81% of PID patients. A family history of PID, sibling death, and/or parental consanguinity would predict 92% of combined immunodeficiencies, 92% of phagocyte defects, 87% of well-identified immunodeficiency syndromes, and 84% of antibody deficiency if the need for intravenous antibiotics is considered in the latter.
Conclusions
The 10 warning signs and IDR score do not aid in an early diagnosis of severe PID. Educational campaigns should target pediatricians aiming to increase PID awareness and to address family history of PID, parental consanguinity, and previous sibling death as key predictors of PID in communities with a high prevalence of consanguineous marriages.
doi:10.4168/aair.2013.5.2.88
PMCID: PMC3579097  PMID: 23450209
Children; Egypt; immunodeficiency disease-related score; primary immunodeficiency diseases; recurrent infection; ten warning signs
22.  A Practical Approach to the Diagnosis of Pelvic Inflammatory Disease 
The diagnosis of acute pelvic inflammatory disease (PID) is usually based on clinical criteria and can be challenging for even the most astute clinicians. Although diagnostic accuracy is advocated, antibiotic treatment should be instituted if there is a diagnosis of cervicitis or suspicion of acute PID. Currently, no single test or combination of diagnostic indicators have been found to reliably predict PID, and laparoscopy cannot be recommended as a first line tool for PID diagnosis. For this reason, the clinician is left with maintaining a high index of suspicion for the diagnosis as he/she evaluates the lower genital tract for inflammation and the pelvic organs for tenderness in women with genital tract symptoms and a risk for sexually transmitted infection. This approach should minimize treating women without PID with antibiotics and optimize the diagnosis in a practical and cost-effective way.
doi:10.1155/2011/753037
PMCID: PMC3148590  PMID: 21822367
23.  Community-based trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial 
Trials  2008;9:73.
Background
Pelvic inflammatory disease (PID) is common and can lead to tubal factor infertility, ectopic pregnancy or chronic pelvic pain. Despite major UK government investment in the National Chlamydia Screening Programme, evidence of benefit remains controversial. The main aim of this trial was to investigate whether screening and treatment of chlamydial infection reduced the incidence of PID over 12 months. Secondary aims were to conduct exploratory studies of the role of bacterial vaginosis (BV) in the development of PID and of the natural history of chlamydial infection.
Design
Randomised controlled trial with follow up after 12 months.
Setting non-healthcare
Common rooms and lecture theatres at 20 universities and further education colleges in Greater London.
Participants
2500 sexually active female students were asked to complete a questionnaire on sexual health and provide self-administered vaginal swabs and smears.
Intervention
Vaginal swabs from intervention women were tested for chlamydia by polymerase chain reaction (PCR) and those infected referred for treatment. Vaginal swabs from control women were stored and analysed after a year. Vaginal smears were Gram stained and analysed for BV.
Main outcome measure
Incidence of clinical PID over 12 months in intervention and control groups. Possible cases of PID will be identified from questionnaires and record searches. Confirmation of the diagnosis will be done by detailed review of medical records by three independent researchers blind to whether the woman is in intervention or control group.
Trial registration
Clinical Trials NCT 00115388
doi:10.1186/1745-6215-9-73
PMCID: PMC2614935  PMID: 19077198
24.  Detection of Pelvic Inflammatory Disease: Development of an Automated Case-Finding Algorithm Using Administrative Data 
ICD-9 codes are conventionally used to identify pelvic inflammatory disease (PID) from administrative data for surveillance purposes. This approach may include non-PID cases. To refine PID case identification among women with ICD-9 codes suggestive of PID, a case-finding algorithm was developed using additional variables. Potential PID cases were identified among women aged 15–44 years at Group Health (GH) and Kaiser Permanente Colorado (KPCO) and verified by medical record review. A classification and regression tree analysis was used to develop the algorithm at GH; validation occurred at KPCO. The positive predictive value (PPV) for using ICD-9 codes alone to identify clinical PID cases was 79%. The algorithm identified PID appropriate treatment and age 15–25 years as predictors. Algorithm sensitivity (GH = 96.4%; KPCO = 90.3%) and PPV (GH = 86.9%; KPCO = 84.5%) were high, but specificity was poor (GH = 45.9%; KPCO = 37.0%). In GH, the algorithm offered a practical alternative to medical record review to further improve PID case identification.
doi:10.1155/2011/428351
PMCID: PMC3226320  PMID: 22144849
25.  Acute Pelvic Inflammatory Disease and Clinical Response to Parenteral Doxycycline 
The bacteriology of acute pelvic inflammatory disease (PID) and clinical response to parenteral doxycycline were evaluated in 30 patients. Only 3 of 21 cul-de-sac cultures from PID patients were sterile, whereas all 8 normal control subjects yielded negative results (P< 0.005). Poor correlation was observed between cervical and cul-de-sac cultures. Neisseria gonorrhoeae, isolated from the cervix in 17 patients (57%), was recovered from the cul-de-sac only once. Streptococcus, Peptococcus, Peptostreptococcus, coliforms, and other organisms normally present in the vagina were the predominant isolates recovered from the cul-de-sac. Parenteral doxycycline resulted in rapid resolution of signs and symptoms (within 48 h) in 20 of 27 evaluable patients (74%). In five others, signs and symptoms of infection abated within 4 days. The remaining two patients failed to respond; in both cases, adnexal masses developed during doxycycline therapy. Gonococci were eradicated from the cervix in all but one patient who, nevertheless, had a rapid defervescence of symptoms. There was no clear-cut correlation between the clinical response and in vitro susceptibility of cul-de-sac isolates to doxycycline. These data confirm the usefulness of broad-spectrum antibiotics in acute PID. Culdocentesis is a reliable means of obtaining material for the bacteriological diagnosis of acute PID; however, the pathogenetic role and relative importance of gonococci and various other bacteria in acute PID need to be clarified further.
PMCID: PMC429092  PMID: 1169908

Results 1-25 (1087149)